1410 Fluids and Electrolytes
Fluids and Electrolytes
Uzer Khan, MBBS, MD
C laude Bernard is quoted as saying, “The living organism does
not really exist in the milieu exterieur (the atmosphere if it
breathes, salt or fresh water if that is its element) but in the liquid
milieu interieur formed by circulating organic liquid, which sur-
rounds and bathes all tissue elements.” This concept of a condensed
ecology within ourselves at the cellular level is crucial to under-
standing the changes pathology imparts on the critically ill. This
understanding allows us to picture the disorders of water balance
and salt balance that plague many surgical patients, both acutely
and chronically.
nn TOTALBODY WATER AND FLUID
COMPARTMENTS
The “water” component of the body makes up approximately 60% of
an individual’s lean body weight. The body divides its water content
into two major compartments (Fig. 1): the extracellular fluid com-
partment (ECF) and intracellular fluid compartment (ICF). These
compartments are divided by a highly selective lipid bilayer, known
as the cell membrane, which allows water to pass freely but not elec-
trolytes. Specifically, the extracellular compartment maintains a rela-
tively higher concentration of sodium, chloride, and bicarbonate,
whereas the intracellular compartment stores higher concentrations
of potassium and phosphate. Further, as the lean proportion of the
body decreases (as in obesity), the total body water percentage also
decreases.
The fluid in the various compartments and the electrolytes that
reside within them are all inextricably linked and interdependent.
This is defined by the concept of osmolarity (mOsm/L). Solutes dis-
solved in water that do not freely traverse a semipermeable mem-
brane are known as osmoles; hence, osmolarity is a measure of the
concentration of osmoles in a solution. Modern laboratories are able
to measure osmoles directly per weight of solution: this is known as
osmolality (mOsm/kg). As can be deduced from the equation, sodium
is by far the most important osmole in plasma with glucose and urea
exerting their effects mostly during disease states such as diabetes and
renal failure respectively:
Posm (mOsm/kg)   =   2 ×  Na
+
  +   [glucose] /18  +  BUN/2.8
in which BUN indicates blood urea nitrogen. The normal osmolality
of plasma ranges from 275 to 290 mOsm/kg.
Finally, plasma tonicity (also known as effective osmolality) is the
parameter that determines the transcellular distribution of water.
Water moves from an area of lower tonicity to an area of higher tonicity
(i.e., from an area of higher water content to an area of lower content).
Tonicity only takes into account the distribution of solutes that do not
freely permeate the cell membrane; this lack of free distribution is what
causes water to shift across cell membranes. Tonicity is differentiated
from osmolality in that certain solutes are ineffective osmoles and are
distributed equally across a cellular membrane (such as urea). Effective
osmoles, on the other hand, do not easily cross a membrane and there-
fore exert an osmolal pressure favoring the retention of water.
This concept is exemplified by the following physiologic scenario:
Renal failure results in the retention of abnormally large concentra-
tions of urea. This can result in an increase in osmolality (see the
formula presented previously), but the tonicity is unchanged because
urea is an ineffective osmole and redistributes freely across cell mem-
branes (i.e., there are equal concentrations in both the ICF and ECF
compartments). If hemodialysis is instituted, urea is rapidly removed
from the ECF. This removal may be faster than urea can equili-
brate across the blood-­brain barrier. Hence, in this scenario, urea
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temporarily acts as an effective osmole and imparts both increased
osmolality and increased tonicity in the cerebral cells. This can result
in water influx and cerebral edema, which can lead to dialysis dis-
equilibrium syndrome.
Fluid Compartments and Regulation of Volume
Sodium homeostasis, through the regulation of urinary sodium
excretion, is the primary determinant of the ECF volume. This is
accomplished through several mechanisms.
In hypovolemia, the renin-­angiotensin-­aldosterone and sympa-
thetic nervous systems (which promote renin secretion) are activated
resulting in sodium retention. Conversely, atrial distension from
hypervolemia results in the release of natriuretic peptides promoting
sodium excretion. Severe hypovolemia that is significant enough to
result in hypotension can trigger the release of antidiuretic hormone
(ADH) as well. In this scenario ADH activates both V2 receptors,
which increase water retention at the level of the distal tubules and
collecting ducts, and V1 receptors, which result in peripheral vaso-
constriction (hence the synonym vasopressin). The primary role of
ADH, however, is in the regulation of plasma osmolality via osmore-
ceptors (rather than volume-­sensitive receptors that activate in severe
hypovolemia). The volume of the extracellular fluid compartment is
thereby regulated.
In a slightly less direct way, the extracellular sodium concentration
also regulates the intracellular fluid volume. Modulation of extracel-
lular sodium results in the alteration of plasma tonicity as described
earlier, which results in the movement of water into or out of the ICF.
This interrelationship is demonstrated in the management of the
acutely brain-­injured patients, a scenario commonly seen in many
intensive care units. The administration of hypotonic intravenous
fluids results in hyponatremia with decreased plasma osmolality and
tonicity (as sodium is an effective osmole). Because water moves from
an area of low tonicity to an area of high tonicity, water would enter
the brain causing cerebral edema and result in worsening of the neuro-
logic insult. The administration of hypotonic fluid in the brain-­injured
patient is, therefore, contraindicated. Conversely, the administration
of hypertonic fluid (such is 3% sodium chloride) results in hypernatre-
mia with increased plasma osmolality and tonicity. This would result in
flow of water out of the brain and decrease cerebral edema; therefore,
the therapeutic increase in plasma sodium levels through the adminis-
tration of hypertonic saline is a common therapy for neurologic injury.
The reverse process occurs in dehydration. Instead of altered
regulation of solute, dehydration results from excessive loss of water
resulting in a significant total body water deficit. This will often result
in a hypernatremia. 
Regulation of Osmolality
As mentioned previously, the primary hormonal mechanism of regu-
lating plasma osmolality is antidiuretic hormone. It is secreted by the
posterior pituitary gland in response to very small changes in plasma
osmolality as detected by the body’s osmoreceptors. Hence, suppres-
sion of ADH is the primary mechanism of protection against water
retention in the setting of low plasma osmolality, whereas the stimu-
lation of thirst is the primary protective mechanism against exces-
sive water loss (by increasing intake) in the setting of elevated plasma
osmolality. ADH may also be secreted in response to large levels of
volume depletion via volume-­sensitive receptors.
The preceding discussion engenders an understanding of normal
physiology and homeostasis. The surgical intensivist will, however,
care for patients suffering derangements of any number of these of
regulatory mechanisms.
Syndrome of Inappropriate ADH
Syndrome of inappropriate ADH (SIADH) is a condition in which the
secretion of ADH is autonomously elevated and unrelated to plasma

Na+
Intracellular compartment
60% total body water K+
Cl–
Ca2+
Mg2+
Po43–
Na+ 144
Interstitial compartment
K+ 4
30% total body water
Cl– 114
Ca2+ 3 not in the latter. The treatment of DI includes a low-­salt, low-­protein
Na+
Mg2+ 2
K+
Po43– 2 nn SPECIFIC
Cl–
Intravascular compartment
10% total body water Ca2+
Mg2+
Po43–
FIG. 1  Distribution and composition (mEq/L) of total body water. Ca2+,
calcium; Cl−, chloride; K+, potassium; Mg2+, magnesium; Na+, sodium; Po43−,
phosphate.
osmolality. This results in an abnormally high amount of free water
retention and subsequent hyponatremia. The syndrome is frequently
seen in postoperative patients and is thought to be related to pain recep-
tor activation. It can, however, occur in a variety of other conditions
including various neurologic disorders (including stroke, trauma, and
hemorrhage), transsphenoidal pituitary surgery, malignancies (particu-
larly small cell cancer of the lung), and drugs (such as carbamazepines,
selective serotonin reuptake inhibitors, haloperidol, opiates, nonste-
roidal antiinflammatory drugs [NSAIDs], valproate, amiodarone,
and ciprofloxacin). The diagnosis should be entertained in patients
with hyponatremia and an appropriate antecedent history. Laboratory
evaluation (Fig. 2) would demonstrate low plasma osmolality (<270
mOsm/kg) with a high urine osmolality (>100 mOsm/kg) and high
urine sodium concentration (>40 mEq/L). These findings in a clinically
euvolemic patient with no recent diuretic use, and no evidence of thy-
roid, adrenal, or pituitary insufficiency can lead to the diagnosis.
The treatment of SIADH is fluid restriction (<1 L/d) and is usu-
ally all that is needed to mediate a gradual increase in plasma sodium
levels. If, however, the hyponatremia is severe and/or symptomatic,
hypertonic saline may be required. This is particularly pertinent in
patients with subarachnoid hemorrhage who develop SIADH, fluid
restriction may precipitate vasospasm and ischemic insults. In this
scenario, therefore, low-­volume 3% hypertonic saline may need to be
administered to gradually raise the sodium level without predispos-
ing to hypovolemia. Additional therapies include the use of oral salt
tablets (9 g/d) and loop diuretics (to increase free water excretion).
The temptation to use isotonic saline should be avoided in all
cases of SIADH because urine osmolality is usually far higher than
the concentration of sodium in isotonic saline. Because sodium han-
dling is intact, all administered sodium will be excreted; however, all
the water will not be excreted since the urine is highly concentrated in
the setting of high plasma ADH levels. Hence, water will be retained
preferentially to sodium and will worsen the hyponatremia.
Finally, the diagnosis of SIADH should not be confused with cere-
bral salt wasting (CSW) syndrome. This is a similar, but much rarer
disorder, with similar laboratory findings but which is characterized
by clinical evidence of hypovolemia.  hyponatremia, the workup entails checking the urine osmolality. A
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SURGIC AL CRITIC AL C ARE 1411
Diabetes Insipidus
10
On the other end of the spectrum of osmolar dysregulation syn-
150 dromes is diabetes insipidus (DI). In this disease state there is either
a deficiency in the body’s ability to secrete ADH (central DI) or in
0
the ability of the distal tubules and collecting ducts to respond to the
0 circulating ADH (nephrogenic DI). Because of the absence or inef-
fectuality of ADH, the kidneys excrete high volumes of dilute urine;
40
hence, DI is diagnosed (Fig. 2) in the presence of a high-­normal
120 serum sodium concentration (>142 mEq/L resulting from free water
loss) associated with polyuria (up to 10 L/day of dilute urine [osmo-
lality <200 mOsm/kg]) and an elevated plasma osmolality (>290
mOsm/kg).
Central DI can be seen after pituitary surgery or trauma, whereas
the most common cause of nephrogenic DI is lithium toxicity. DDAVP
(desmopressin) can help differentiate the two diseases; administra-
tion results in improvement of urine osmolality in the former, but
142 diet, diuretics, and NSAIDs supplemented by DDAVP in central DI. 
5
ELECTROLYTE DISORDERS
103
Sodium
5
Plasma sodium levels are directly affected by fluid balance. Hypona-
3 tremia results from excess water intake that is not excreted, whereas
hypernatremia results from an excessive loss of free water.
2
Hyponatremia is defined as a sodium level less than 135 mEq/L
(mild, 130–134 mEq/L; moderate, 120–129 mEq/L; severe, <120
mEq/L). True hyponatremia that is secondary to excess plasma free
water retention will result in decreased plasma osmolality; this is the
most common kind of hyponatremia in surgical patients and is con-
sidered hypotonic hyponatremia. There are certain conditions, how-
ever, that can result in hyponatremia without a decrease in plasma
osmolality; therefore, a serum osmolality is generally the first step in
the workup of hyponatremia. If the plasma is isotonic, the “hypona-
tremia” occurs in the context of abnormally elevated lipid or plasma
protein levels. This is known as a pseudohyponatremia because the
decreased sodium level is an artifact of older laboratory measurement
techniques that uses the total plasma volume rather than the aqueous
portion when measuring the sodium levels. If the plasma is hypertonic,
this indicates the presence of a significant number of minor osmoles
contributing to hypertonicity in lieu of sodium; this can occur with,
for example, severe hyperglycemia or in the presence of high levels of
mannitol. These osmoles cause free water to move from the ICF to the
ECF and result in a decreased plasma sodium level. In hyperglycemia,
this level of sodium can be predicted: for every 100 mg/dL increase in
glucose levels, the plasma sodium will decrease by 2.4 mEq/L on aver-
age. This association is nonlinear and, in fact, a correction factor of
4.0 may be needed for glucose levels above 400 mg/dL. Similarly, the
use of surgical irrigants such as during a transurethral resection of the
prostate or bladder or hysteroscopy can lead to hyponatremia through
the absorption of hypotonic water and the expansion of the ECF. In
all these scenarios, treating the underlying source of increased plasma
tonicity will address the hyponatremia.
Once a true hypotonic hyponatremia is diagnosed, the volume sta-
tus needs to be assessed. Patients who are overtly hypervolemic likely
have an underlying disorder that results in total body water retention,
but with diminished effective intravascular circulation. This can result
from disease processes such as cirrhosis, congestive heart failure,
nephrotic syndrome, and hypoalbuminemia. The diminished intra-
vascular circulating volume results in the nonosmotic stimulation of
ADH release leading to free water retention despite the underlying
hypervolemic status. The hyponatremia is generally asymptomatic
and chronic in nature precluding the need for rapid reversal in situa-
tions of mild or moderate hyponatremia. In general, the mainstay of
treatment is fluid restriction.
Euvolemic hyponatremia is the most common cause of hypo-
natremia in the hospitalized patient. After confirmation of a true
1412 Fluids and Electrolytes

Hyponatremia

Measure serum osmolarity

>290 mOsm/L <275 mOsm/L 275–290 mOsm/L

Hypertonic Hypotonic Isotonic

Hyperglycemia Hyperlipidemia
Hypertonic solutions Hyperproteinemia
(mannitol)

Assess volume status

Hypovolemic Euvolemic Hypervolemic

Measure urine sodium Measure urine osmolality Measure urine sodium

Renal (>20 mEq/L) <100 mOsm/L Renal (>20 mEq/L)

Adrenal/mineralocorticoid Water intoxication Renal failure
deficiency
Diuretics >100 mOsm/L Extrarenal (<10 mEq/L)
Osmotic diuresis SIADH Congestive heart failure
Cerebral salt wasting Adrenal insufficiency Cirrhosis
Hypothyroidism Nephrotic syndrome
Extrarenal (<10 mEq/L)
Gastrointestinal losses
Vomiting
Nausea
Diarrhea
Ileus/obstruction
Skin losses
Burns
Open wounds
Hemorrhage/blood loss
A

Hypernatremia

Assess fluid volume

Low Normal High

Extrarenal fluid losses Renal fluid losses Hyperaldosteronism

(Urine Osm >700) (Urine Na >20) Cushing’s syndrome
Vomiting Insensible losses Hypertonic saline
Diarrhea Burns/wounds Hypertonic bicarbonate
NGT suctioning Fever/sweat Hypertonic dialysis
Burns/wounds
Fever/sweat Diabetes insipidus
(Urine Na <10)
Renal fluid losses Nephrogenic DI
(Urine Osm <700) Central DI
Osmotic diuresis
Diuretic use
Polyuric phase ATN
Postobstructive diuresis
B
FIG. 2  (A) Hyponatremia. (B) Hypernatremia. ATN, acute tubular necrosis; DI, diabetes insipidus; Na, sodium; NGT, nasogastric tube; Osm, osmolality; SIADH,
syndrome of inappropriate antidiuretic hormone secretion.

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high urine osmolality implies the presence of SIADH and an internal
homeostasis disorder (see the previous section), whereas a low urine
osmolality suggests excessive exogenous intake (water intoxication).
Hypovolemic hyponatremia is the most common cause of hypona-
tremia in the postoperative state and can be seen in conditions of high
fluid loss such as through the gastrointestinal (GI) tract, fluid seques-
tration (third-­spacing), or from hemorrhage. Again, the volume loss
results in a nonosmotic stimulation of ADH release and the retention
of free water resulting in hyponatremia and concentrated urine with
a low sodium concentration (<10 mEq/L). Primary renal losses can
lead to a similar clinical condition except with a more elevated urine
sodium level (>20 mEq/L). Finally, large volume sodium depletion
can occur in the CSW. This syndrome can occur in the setting of brain
injury and results in the active excretion of sodium with high levels
in the urine (>40 mEq/L). In contrast to SIADH, fluid restriction will
compound the hyponatremia because there is an underlying hypovo-
lemia in CSW. Volume and salt repletion, such as with isotonic intra-
venous fluids, is therefore the mainstay of treatment.
An important consideration in the management of hyponatremia
is the rate of correction. Patients with chronic hyponatremia are at
much higher risk for central pontine myelinolysis than those who
develop hyponatremia acutely (within 48 hours). In the former situ-
ation, a slow correction of the hyponatremia should be considered
(0.25–0.5 mEq/L per hour). Correction that is too rapid can pre-
dispose to the development of central pontine myelinolysis, which
generally occurs 2 to 6 days after the sodium correction. Symptoms
include dysarthria, paresis, seizures, lethargy, and coma among oth-
ers. Symptoms tend to be irreversible. Severely afflicted patients
may experience locked-­in syndrome, in which patients are awake but
unable to communicate except through eye movements. In acute
hyponatremia, a faster correction (1–2 mEq/L per hour) is safe and
can be accomplished through the infusion of 3% hypertonic saline.
Hypernatremia is defined as a sodium level greater than 145
mEq/L (moderate, 146–159 mEq/L; severe, ≥160 mEq/L). Clinical
signs include restlessness and insomnia but can progress to lethargy
and coma at extremely high sodium levels. Similar to hyponatremia,
hypernatremia can occur in all variations of intravenous volume.
In the surgical patient, hypovolemic hypernatremia is the most
common scenario and is secondary to unreplaced water loss. This can
be secondary to GI losses such as nasogastric suctioning, vomiting
and diarrhea; renal losses such as with diuretic use; or with multiple,
large open wounds (e.g., burns) resulting in evaporative losses. A
key differentiating factor is that renal losses will have elevated urine
sodium loss (>20 mEq/L) compared with decreased urine excretion
in other etiologies.
Euvolemic hypernatremia most commonly develops in the con-
text of DI (see the previous section). Hypervolemic hypernatremia
is usually iatrogenic and related to large volume administration of
isotonic or hypertonic saline. Mineralocorticoid or glucocorticoid
excess may also cause similar findings (Conn’s and Cushing’s syn-
drome, respectively).
Irrespective of the volume status of the patient, however, all
patients of hypernatremia have a free water deficit; therefore, the
treatment of hypernatremia revolves around the administration of
hypotonic fluid and may be supplemented with diuresis in hypervol-
emic states. To accomplish this, the free water deficit should be calcu-
lated and can be done with the following formula:
[Naplasma ]−140
Free water deficit = × Total body water
140
In general, half the calculated water deficit is replaced in the first
24 hours, and the remaining half over the next 24 hours. The choice
of fluid used to correct the hypernatremia depends on any other
ongoing electrolyte abnormalities and the underlying etiology. In
general, hypernatremia is treated with the administration of hypo-
tonic fluid (oral or intravenous) such as 0.45% saline or D5 water;
however, if the hypernatremia is associated with hypovolemia (i.e.,
both fluid and salt loss) additional solute may be required such as
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SURGIC AL CRITIC AL C ARE 1413
with the administration of more isotonic solutions such as 0.9% nor-
mal saline or lactated ringers. A further consideration is the rate of
correction: acute hypernatremia (within 48 hours) is generally safe
to reverse rapidly (1–2 mEq/L per hour for example), but rapidly
correcting hypernatremia that is more chronic can lead to cerebral
edema. Hence, chronic hypernatremia should not be corrected at a
rate faster than 0.5 mEq/L per hour. 
Chloride
Chloride is the second most abundant electrolyte in the ECF. Its pri-
mary roles are in its contribution to osmolality as well as muscular
function, GI and pulmonary function, as well as urine concentration
by the kidney.
The primary method of chloride homeostasis is via excretion
through the kidney and its range is maintained between 97 and 107
mEq/L. Hyperchloremia is generally seen in situations of dehydration
where it is paired with a hypernatremia such as with large-­volume
diarrhea. These situations entail the development of a normal anion
gap metabolic acidosis (i.e., high loss of bicarbonate and retention of
chloride). Biliary and pancreatic fistulas are other important causes.
Iatrogenic hyperchloremia is common secondary to the large volume
administration of acidic isotonic fluid such as 0.9% normal saline,
which has a much higher concentration of chloride (154 mEq/L)
compared with plasma (<110 mEq/L). Consequently, a rise in chlo-
ride leads to a drop in serum bicarbonate and a hyperchloremic meta-
bolic acidosis.
Conversely, hypochloremia is generally associated with a meta-
bolic alkalosis and may be physiologic as in physiologic chloriduria
where renal excretion of chloride is increased in exchange of bicar-
bonate reabsorption as a compensatory response in the setting respi-
ratory acidosis. Primary hypochloremia is usually secondary to GI
losses such as congenital chloride diarrhea, nasogastric suctioning,
and high ileostomy output, which preferentially lose high volumes of
chloride. In these scenarios, the fluid lost may also have a relatively
low bicarbonate content relative to the ECF. The water loss leads to
contraction of the ECF with a relatively stable bicarbonate concentra-
tion and a contraction alkalosis. Uncontrolled renal losses, such as
with diuretic therapy or renal failure, can also contribute to a hypo-
chloremic metabolic alkalosis. 
Potassium
Unlike sodium and chloride, potassium is primarily an intracellular
cation. Potassium is the primary determinant of the resting mem-
brane potential across the cell membranes of most cells and that is
why alterations can lead to dysrhythmias and cardiac abnormalities.
Its homeostasis is maintained primarily through renal excretion.
Hypokalemia is a common condition particularly in the postop-
erative state. It is defined as a serum potassium value of less than 3.5
mEq/L. Hypokalemia can occur through GI losses, renal losses, alka-
losis, the administration of insulin, as well as others (Table 1). Patients
complain of nonspecific symptoms such as fatigue and weakness, and
hypokalemia can predispose to intestinal ileus. Severe hypokalemia
can lead electrocardiogram changes such as T-­wave flattening.
In addition, most of the causes of hypokalemia also predispose to
hypomagnesemia. These patients are likely to be refractory to replace-
ment of potassium alone without treating the hypomagnesemia as
well; hence, magnesium levels should be checked and repleted in all
hypokalemia patients. Potassium can be replaced orally or intrave-
nously. The latter is generally considered in patients with more severe
hypokalemia and should be administered in a monitored setting due
to the risk of arrhythmias.
Oral repletion of potassium is a frequent necessity for surgical ser-
vices. The healthcare provider should be cognizant of not administer-
ing a high potassium load through the GI tract all at once because
it can lead to nausea and vomiting. Potassium is, therefore, gener-
ally repleted over 4 to 6 divided doses (Table 2). In all conditions of
1414 Fluids and Electrolytes

TABLE 1  Causes of Abnormal Potassium Levels

Hypokalemia Hyperkalemia
EXTRARENAL LOSSES EXTRARENAL CAUSES
• Diarrhea • Pseudohyperkalemia
• Malabsorption • Metabolic acidosis
• VIPomas • Succinylcholine
• ZE syndrome • Beta-­2 adrenergic antagonists
• Villous adenomas • Digoxin
INTRACELLULAR POTASSIUM SHIFT • Rhabdomyolysis
• Metabolic alkalosis • Tumor lysis syndrome
• Beta-­2 adrenergic agonists • Ethanol or methanol
• Theophylline • Salicylates
• Caffeine • Insulin deficiency
• Hyperthyroidism RENAL ETIOLOGIES
RENAL LOSSES • Renal failure
• Diuretics (loop, thiazide, and osmotic agents) • Mineralocorticoid deficiency (first-­degree
• Other medications (amphotericin B, cisplatin, foscarnet, aminoglycosides) hypoaldosteronism, Addison’s disease, ACE inhibitors,
• Hyperaldosteronism (Conn’s syndrome, Cushing’s syndrome, dehydration) ARBs, NSAIDs)
• Magnesium deficiency • Mineralocorticoid resistance (spironolactone,
• Delirium tremens trimethoprim, cyclosporine, tacrolimus)
ACE, Angiotensin-­converting enzyme; ARBs, angiotensin receptor blockers; NSAIDs, nonsteroidal antiinflammatory drugs; ZE, Zollinger-­Ellison.

TABLE 2  Example of Electrolyte Replacement Protocola

Serum Level (mg/dL) Replacement Dose

POTASSIUMb
3.3–3.9 40 mEq KCl PO/IV
3.0–3.2 60 mEq KCl PO/IV
2.6–2.9 80 mEq KCl IV
<2.6 100 mEq IV
MAGNESIUMc
1.6–1.9 4 g MgSO4 IV or 250 mg MgO PO × 2 dosesd
1.0–1.5 6 g MgSO4 IV
<1.0 8 g MgSO4 IV
PHOSPHORUSe
2–2.5 20 mmol Na-­Phos or K-­Phos (provides ∼30 mEq K+)
1.6–1.9 30 mmol Na-­Phos or K-­Phos (provides ∼44 mEq K+)
<1.6 40 mmol Na-­Phos or K-­Phos (provides ∼60 mEq K+)
CALCIUMf,g
3.5–3.9 2 g IV Ca-­gluconate
3.0–3.4 4 g IV Ca-­gluconate
<2.9 6 g IV Ca-­gluconate
aExcludes patients on dialysis or with creatinine clearance <20 mL/min.
bIV KCl infusion rate should not exceed 10 mEq/hr through peripheral line or 40 mEq/hr using central line and continuous cardiac monitoring.
cIV MgSO infusion rate should not exceed 2 g/hr.
4
dOral magnesium replacement should be avoided in patients with poor oral tolerance or GI disturbance.
eFor simultaneous K+ replacement, subtract the amount given with K-­Phos and give remainder as KCl.
fIonized calcium, 1 mg/dL = 0.25 mmol/dL.
gIV Ca-­gluconate infusion rate should not exceed 2 g/hr; for CaCl, give one-­third dose using central line and continuous cardiac monitoring.

CaCl, Calcium chloride; Ca-­gluconate, calcium gluconate; GI, gastrointestinal; IV, intravenous; K+, potassium; KCl, potassium chloride; K-­Phos, potassium
phosphate; MgO, magnesium oxide; MgSO4, magnesium sulfate; Na-­Phos, sodium phosphate; PO, per os (oral).

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hypokalemia, the renal function must be evaluated. Aggressive reple-
tion may be inappropriate in patients with renal insufficiency as they
have a reduced capacity for potassium excretion.
Hyperkalemia is defined as a potassium level exceeding 5.5 mEq/L.
A frequent cause of an elevated laboratory value of serum potassium
is due to hemolysis of lab specimens. The serum potassium should
be repeated in these cases. The etiology of hyperkalemia can be from
a variety of sources and includes mineralocorticoid deficiency, renal
failure, ischemia-­reperfusion injury, and the use of succinylcholine in
certain clinical conditions such as burns or major trauma.
True hyperkalemia will result in muscle weakness and cardiac
conduction abnormalities. This usually occurs with severe hyperka-
lemia (≥7.0 mEq/L) or lesser elevations that occur acutely. Cardiac
abnormalities include peaked T waves and shortened QT intervals.
Symptomatic hyperkalemia, hyperkalemia of more than 6.5 mEq/L,
and/or hyperkalemia in the presence of renal impairment or other
sources of ongoing potassium absorption are considered hyperkale-
mic emergencies. In these scenarios the management of hyperkale-
mia should be implemented in two paradigms:
1. Rapidly acting therapies that mobilize potassium back into the
cells.
2. Therapies that remove potassium from the body.
  
In hyperkalemic emergencies rapidly acting therapies should be
implemented. This includes the administration of IV calcium (e.g.,
1000 mg of intravenous calcium gluconate over 30 to 60 minutes)
to antagonize the effects of potassium on the cell membranes and to
provide a membrane stabilizing effect. In addition, 10 U of intrave-
nous insulin should be administered be administered to mobilize
potassium into the cells. To prevent hypoglycemia, dextrose may be
administered in addition to the insulin (e.g., 50 mL of 50% dextrose
solution).
It should be emphasized that the aforementioned therapies are
temporizing maneuvers and do nothing to alter the total body potas-
sium content. To truly decrease the body’s potassium levels other
therapies will need to be instituted. These therapies include the
administration of diuretics, gastrointestinal cation exchangers, and
the use of hemodialysis.
The administration of loop diuretics can lead to a kaliuresis and
decrease the body’s potassium levels. This is particularly helpful in
cases of preserved renal function; however, most patients with refrac-
tory hyperkalemia will have some element of renal dysfunction. In
these patients, loop diuretics should not be used in isolation.
The use of sodium polystyrene sulfonate has historically been fre-
quently cited as a therapy to remove potassium through the GI tract,
but studies have shown that complications are frequent and include
intestinal necrosis. Sodium polystyrene sulfonate should therefore
only be used as a last resort. Other cation exchangers, such as pati-
romer, may be used instead.
The mainstay of therapy for hyperkalemia is hemodialysis and
should be instituted as soon as possible. Other therapies may not be
necessary if dialysis and vascular access are immediately available.
The administration of beta-­2 adrenergic agonists and sodium
bicarbonate may be considered as supplements to the therapies dis-
cussed previously.  ciency, hyperphosphatemia, hypomagnesemia, and malnutrition. In
Magnesium
Magnesium is also an electrolyte the majority of which resides in
the ICF. Hypomagnesemia is defined as a serum level of <1.6 mg/
dL and is common in surgical patients with GI losses, dilution, or
those with poor oral intake. Symptoms include tetany, seizures, and
dysrhythmias. Repletion can be done orally or parenterally, how-
ever, oral repletion should be used with caution as diarrhea can
sometimes be precipitated. Furthermore, rapid repletion of serum
levels may inhibit renal reabsorption of magnesium; therefore,
severe hypomagnesemia should be managed with more prolonged
infusion (6–12 hours). Conversely, magnesium administered to
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SURGIC AL CRITIC AL C ARE 1415
abort certain dysrhythmias (e.g., torsades de pointes) should be
infused rapidly.
Hypermagnesemia occurs with serum levels greater than 2.8 mg/
dL. Symptoms include decreased deep tendon reflexes, lethargy, and
cardiac conduction abnormalities. Because of the efficiency with
which the kidneys clear magnesium, hypermagnesemia is an uncom-
mon entity. It generally occurs in renal insufficiency or in the context
of a large magnesium load. In the setting of normal renal function,
loop diuretics may be used to help clear the hypermagnesemia. In
addition, patients with renal sufficiency may need hemodialysis.
Symptomatic hypermagnesemia should be temporized with the
administration of intravenous calcium to counteract magnesium’s
effects in precipitating abnormal cardiac conduction and its effects
on the neurologic system. 
Calcium
Calcium is the most abundant electrolyte in the body but mostly
exists in a mineralized state in the skeletal system. The normal range
of total serum calcium is 8.5 to 10.5 mg/dL, and the normal range of
the active, ionized form of calcium is 4.65 to 5.25 mg/dL. This ion-
ized portion constitutes approximately 45% of the plasma calcium.
The rest is bound to albumin (40%) or complexed to anions such as
phosphate and citrate (15%). The consequence of this is that serum
albumin concentration has a direct correlation to the measured total
calcium concentration, a decrease in albumin of 1 g/dL leads to a
measured decrease of 0.8 mEq/L of serum calcium (therefore requir-
ing correction of any laboratory measurements of total calcium).
Calcium homeostasis is accomplished via the hormones parathyroid
hormone (PTH), vitamin D (calcitriol), and calcitonin (Fig. 3).
1. P TH is secreted by the parathyroid glands in response to hypo-
calcemia. This leads to an increase in calcium levels (via stimu-
lation of osteoclasts and kidney reabsorption) and a decrease in
phosphate levels (via excretion by the kidneys). The increased
phosphate excretion allows the liberated calcium to remain in the
plasma as the active, ionized form.
2. PTH also stimulates the production of vitamin D in the kidneys,
which further stimulates the reabsorption of calcium from the
gastrointestinal tract and kidney. Vitamin D also stimulates bone
resorption and remodeling.
3. Calcitonin is produced by the parafollicular cells of the thyroid
gland and serves to decrease calcium levels by inhibiting bone
resorption.
  
Hypocalcemia occurs if the plasma calcium level falls below 8.4
mEq/L (or an ionized calcium of <4.5 mEq/L). Classic symptoms
of hypocalcemia include perioral numbness and tingling, twitching
of the facial muscles on tapping the facial nerve in the region of the
parotid gland (Chvostek’s sign), and carpopedal spasm at the level
of the hand and forearm precipitated by ischemia, such as by the
application of a blood pressure cuff on the ipsilateral arm (Trous-
seau’s sign). Electrocardiogram findings include a prolonged QT
interval and arrhythmias. Hypocalcemia is often seen after thyroid
and parathyroid surgery, severe acute pancreatitis, vitamin D defi-
the critically ill population, hypocalcemia develops frequently and is
likely a consequence of suppressed PTH and vitamin D production,
as well as end-­organ resistance to the actions of PTH likely second-
ary to decreased magnesium levels and the effects of inflammatory
cytokines. Large-­volume blood transfusion can also predispose to
hypocalcemia because the citrate used as an anticoagulant acts as a
calcium chelator (the total calcium is thereby detected as normal but
in effect the level of ionized calcium is low). Hypocalcemia should be
treated if the levels fall below a total calcium of 7 mEq/L (ionized cal-
cium <3 mEq/L), or if symptoms develop. This repletion is frequently
through the intravenous route in the form of calcium gluconate or
calcium chloride. The latter formulation has three times the elemental
calcium of the former; it can rapidly reverse deficiencies but infusions
1416 Fluids and Electrolytes

↓ ECF (Ca2+)

Thyroid gland

Parathyroid
glands

↑ Parathyroid hormone

Small
intestine

↑ Ca2+ absorption ↑ Bone absorption

↑ Ca2+ absorption ↑ Phosphate excretion Ca2+ into ECF

↑ ECF (Ca2+)

FIG. 3  Calcium homeostasis. Ca2+, Calcium; ECF, extracellular fluid.

need to be through central venous catheters and in a monitored set-
ting. Oral calcium carbonate or calcium gluconate can be used in
chronic or milder forms of hypocalcemia.
Hypercalcemia is defined as a total calcium level above 10.4
mEq/L (>5.6 mEq/L ionized calcium) and is represented by a classic
constellation of symptoms (and an oft-­repeated mnemonic): myal-
gias and arthralgias (“painful bones”), the development of “kidney
stones,” nausea, vomiting (“abdominal groans”), lethargy, and altered
mental status (“psychic moans”). Hypercalcemic crisis can occur
with levels over 14 mEq/L. The most common cause of hypercalce-
mia in nonhospitalized patients is hyperparathyroidism, whereas it is
malignancies (such as breast, lung, and multiple myeloma) that cause
hypercalcemia more frequently in hospitalized patients. Other causes
include immobilization, familial hypocalciuric hypercalcemia, thy-
rotoxicosis, and medications such as thiazide diuretics and lithium.
Treatment should be instituted for severe elevations (>14 mEq/L) or
if symptoms are present, including the following.
1. I sotonic saline to correct any fluid losses related to hypercalcemia-­
induced urinary salt wasting and vomiting. An initial rate may
need to be as high as 200 to 300 mL/hr until adjustments can take
place to maintain a urine output of 100 to 150 mL/hr.
2.  Intramuscular or subcutaneous calcitonin should be admin-
istered concurrently at a starting dose of 4 IU/kg every 6 to 12
hours. This allows for increased urinary excretion and decreased
bone breakdown.
3. Finally, bisphosphonates, such as pamidronate, should also be
administered. Bisphosphonates interfere with osteoclast-­mediate
bone resorption. Although the administration of bisphosphonates
is the most potent treatment, their peak effect does not occur until
2 to 4 days after administration; therefore, combination therapy
with saline and calcitonin (which reduces calcium levels more
rapidly) is the mainstay of treatment. 
Phosphorus
Similar to calcium, the majority of phosphorus is also contained in
the bone and is also regulated by PTH and vitamin D. Hypophos-
phatemia occurs if the phosphorus level falls below 2.5 mg/dL and
is seen frequently in the postoperative setting especially after hepatic
resections. If severe, deficiencies can lead to heart and respiratory
failure. Refeeding syndrome is also an important and common cause
of hypophosphatemia in the critically ill and malnourished. Other
causes include the administration of diuretic medications, intesti-
nal malabsorption, vitamin D deficiency, and hyperparathyroidism.
Repletion can occur via the oral or parenteral route. Hyperphospha-
temia can occur after parathyroid or thyroid surgery; the symptoms
are usually related to the concomitant hypocalcemia. In the acute set-
ting this is treated with volume expansion. Chronic hyperphospha-
temia, however, is seen commonly in renal failure and can be treated
with phosphate binders. 

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nn SUMMARY
The preceding discussion should impart to the reader the inter-
relatedness of the fluid milieu of the human body, whether the
intracellular or the extracellular components, and the salts that
are dissolved within it. Successful recognition and management of
these complex problems requires a patient and systematic evalua-
tion while recognizing the pitfalls of perfecting electrolyte abnor-
malities that may be appropriate physiologic responses or chronic
derangements.
Acid-­Base Problems
Ana M. Velez-Rosborough, MD, and Marko Bukur, MD,
FACS
T he human body’s tightly regulated pH of 7.35 to 7.45 is vital
to maintaining homeostasis for a variety of physiologic
functions including oxygen transport, cardiac electrophysiology,
neurotransmission, enzymatic activity, and drug metabolism, among
others. Different stressors, including trauma, surgical intervention,
and critical illness, can precipitate acid-­base disturbances that may
result as a direct consequence of these inciting events or as a result of
preexisting comorbid conditions.
Different theories exist to explain acid-­base physiology, the most
prominent of which is the traditional model. Alternative methods of
acid-­base analysis such as Stewart’s physiochemical model exist and
are beyond the scope of this summary. In clinical practice, one theory
has not been shown to be superior to the other and both are limited as
they describe the state of a biologic solution at the moment of analy-
sis. The traditional model is based on Brønsted and Lowry’s theory,
which characterizes acids as hydrogen ion (H+) donors and bases as
H+ acceptors. This is based on the notion that any change in con-
centration of H+ in the body results in a compensatory response to
restore the pH into normal range. As determined by the Henderson-­
Hasselbalch equation, the traditional model uses measured concen-
trations of plasma carbon dioxide (CO2) and bicarbonate (HCO3−) to
determine the pH of blood. This equation is shown below where pK
is the acid dissociation constant, 0.03 is the solubility constant of CO2
in the blood, and PaCO2 is the partial pressure of carbon dioxide in
the arterial blood.
pH = pK + log10 [HCO3– /0.03 ( PaCO2 )]
nn ACID-­BASE HOMEOSTASIS
The narrow pH range of body fluids is maintained despite the normal
acid loads produced as a byproduct of metabolism. To maintain this
stable plasma acid-­base balance, endogenous acid load is efficiently
neutralized by a combination of mechanisms that vary temporally
and can be used to help determine the acuity of the disorder present.
These include extracellular and intracellular buffer systems (which act
in minutes), changes in alveolar ventilation (which occurs in hours),
and renal excretion (which takes days). When acid-­base disturbances
are present, existing physiologic adaptations are better at combating
acidosis than alkalosis.
Buffer Systems
Proteins and phosphates are the main intracellular buffers, whereas
hemoglobin is the main buffer within red blood cells, with histidine
moieties acting as H+ binding sites. The bicarbonate–carbonic acid
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SURGIC AL CRITIC AL C ARE 1417
Suggested Readings
Kaplan LJ, Kellum JA. Fluids, pH, ions and electrolytes. Curr Opin Crit Care.
2010;16(4):323–331.
Hashem R, Weissman C. Renal dysfunction and fluid and electrolyte distur-
bances. Curr Opin Crit Care. 2011;17(4):390–395.
Lee JW. Fluid and electrolyte disturbances in critically ill patients. Electrolyte
Blood Press. 2010:8(2):72–81.
Buffington MA, Abreo K. Hyponatremia: a review. J Intensive Care Med.
2016;31(4):223–236.
Berend K, van Hulsteijn LH, Gans RO. Chloride: the queen of electrolytes?
Eur J Intern Med. 2012;23(3):203–211.
system is the most prominent extracellular buffer, whereas plasma
proteins such as albumin and inorganic phosphates contribute to a
lesser extent. Bone, although not an acute buffer, can absorb H+ in
exchange for sodium (Na+) and potassium (K+), and releases calcium,
HCO3−, carbonate, and phosphates. 
Respiratory System
In patients with normal gas exchange, CO2 diffuses quickly and is
cleared via compensatory changes in alveolar ventilation in response
to pH changes sensed in the carotid body and by medullary chemore-
ceptors. This leads to rapid changes in PaCO2. 
Renal System
The proximal tubule modulates both H+ secretion and resorbs 85% of
the filtered HCO3−. Additionally, the distal tubule functions to excrete
H+, either in exchange for Na+, or in combination with ammonia as
ammonium chloride (NH4Cl). 
nn DISORDERS OF ACID-­BASE METABOLISM
Acid-­base disorders occur when there is a lack of balance between the
production of acids and bases and the body’s ability to compensate.
This may be due either to a rapid rate of production or a defect in
the physiologic compensatory mechanisms. These disturbances are
markers of an underlying disease process. Correction of abnormali-
ties should occur while simultaneously searching for inciting causes.
Acidemia is defined as a plasma pH less than 7.35, and alkalemia
is defined as a plasma pH greater than 7.45. These definitions are a
reflection of the serum pH, not necessarily a reflection of the acid-­
base disorders that collectively may or may not lead to pH altera-
tion. Acidosis is defined as any process that lowers the pH (increases
H+) and alkalosis any process that increases the pH (decreases H+).
Acid-­base disorders can develop as a result of metabolic or respi-
ratory alterations. Additionally, multiple acid-­base disorders can
exist at one time and can be uncovered by examining the expected
and observed compensatory changes in PaCO2 and HCO3−, respec-
tively. It is important to note that “compensatory” responses to the
primary acid-­base disturbance occur in the same direction and are
only partially corrective. For example, in metabolic acidosis the
serum HCO3− level decreases with a physiologic decrease in the
PaCO2 through increased minute ventilation. Estimates of physi-
ologic responses are depicted in Table 1. If compensation is greater
or less than predicted, that is, the PaCO2 or HCO3− is not within
the range predicted by the formula, it is important to evaluate for a
mixed acid-­base disorder.
Physiologic Effects of Acidosis and Alkalosis
Acutely, acidosis has physiologic benefits, such as enhanced periph-
eral oxygen delivery by decreased binding of oxygen to hemoglobin
and catecholamine and aldosterone stimulation augmenting cardiac