The n e w e ng l a n d j o u r na l of m e dic i n e

Review Article

Disorders of Fluids and Electrolytes

Julie R. Ingelfinger, M.D., Editor

Maintenance Intravenous Fluids

in Acutely Ill Patients
Michael L. Moritz, M.D., and Juan C. Ayus, M.D.​​

A 
From the Department of Pediatrics and critical aspect of the care of acutely ill patients is the admin-
Division of Nephrology, Children’s Hos- istration of intravenous fluids. Intravenous fluids may be required as a
pital of Pittsburgh of the University of
Pittsburgh Medical Center (UPMC), Uni- bolus infusion for resuscitation or as a continuous infusion when sufficient
versity of Pittsburgh School of Medicine, fluids cannot be ingested orally.
Pittsburgh (M.L.M.); Renal Consultants The goal of maintenance intravenous fluids is to preserve the extracellular vol-
of Houston, Houston (J.C.A.); and the
Division of Nephrology, Hospital Italiano ume while maintaining a normal electrolyte balance. An appropriate maintenance
de Buenos Aires, Buenos Aires (J.C.A.). fluid provides an adequate quantity of both water and electrolytes to ensure good
Address reprint requests to Dr. Moritz at tissue perfusion without causing complications related to fluid overload or volume
the Division of Nephrology, Children’s
Hospital of Pittsburgh of UPMC, 1 Chil- depletion. It also prevents the development of hyponatremia, hypernatremia, and
dren’s Hospital Dr., 4401 Penn Ave., other electrolyte imbalances.
Pittsburgh, PA 15224, or at m ­ oritzml@​ Despite the almost ubiquitous need for intravenous fluids in acutely ill pa-
­upmc​.­edu.
tients, there has been little consensus on the most appropriate rate of adminis-
N Engl J Med 2015;373:1350-60. tration and composition of intravenous fluids, and practice patterns with respect
DOI: 10.1056/NEJMra1412877
Copyright © 2015 Massachusetts Medical Society. to maintenance fluids vary widely.1-3 In addition, acutely ill patients frequently
have conditions that impair normal water and electrolyte homeostasis (Table 1),
and choosing the appropriate volume and composition of intravenous fluids requires
great care.4
Intravenous fluids can be classified, according to the concentration of sodium
plus potassium in the fluid, as being either isotonic (approximately equal to the
plasma sodium concentration) or hypotonic (less than the plasma sodium concen-
tration). The dextrose content of intravenous fluids has no effect on the tonicity,
since the dextrose is rapidly metabolized when it enters the bloodstream and
should not produce hyperglycemia.
A prevailing practice has been to administer hypotonic maintenance intrave-
nous fluids in both children and adults.1,5,6 This practice has been associated with
a high incidence of hospital-acquired hyponatremia and more than 100 reports of
iatrogenic deaths or permanent neurologic impairment related to hyponatremic
encephalopathy,7-11 since acutely ill patients may have disease states associated
with an excess of arginine vasopressin (AVP) (Fig. 1). This excess impairs excretion
of free water and may aggravate hyponatremia.15,16
Over the past decade, many studies have evaluated the association between the
composition and quantity of maintenance fluids and the development of hypona-
tremia. Recent data also suggest that rapid volume expansion with 0.9% saline
(normal saline), as compared with balanced electrolyte solutions, may result in
untoward complications.17 The current review considers the physiological princi-
ples that guide the appropriate selection of intravenous fluids, as well as the recent
literature evaluating the safety of various intravenous fluids with respect to their
composition and rate of administration.

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 Maintenance Fluids in Acutely Ill Patients

AV P a nd Disor der s of Sodium Table 1. Conditions Requiring Special Considerations in Maintenance Fluid
a nd Water Homeos ta sis Therapy.

The human body has a remarkable ability to main- Free-water restriction for euvolemic states of AVP excess
tain a normal composition of body water and CNS disturbances
plasma osmolality, despite wide variations in Meningitis
fluid and electrolyte intake.18 Sodium and water Encephalitis
homeostasis is regulated through the actions of Brain tumors
AVP, the renin–angiotensin–aldosterone system, Head injury
and natriuretic peptides. Plasma osmolality is Cerebritis
regulated both by thirst and by excretion of free Subarachnoid hemorrhage
water. In a patient who can ingest nothing by Pulmonary disease
mouth, plasma osmolality is primarily under the Pneumonia
control of AVP release, which determines the Asthma
rate of free-water excretion.12 Any disease state Bronchiolitis
that results in either excess AVP or impaired AVP Tuberculosis
action will place a patient at risk for a plasma Cancer
sodium concentration that is too high or too low. Postoperative state
There are numerous hemodynamic and non- Fluid restriction for edematous states
hemodynamic stimuli for AVP secretion; thus, Congestive heart failure
virtually all acutely ill hospitalized patients are Nephrosis
at risk for hyponatremia (Fig. 1). Hemodynamic Cirrhosis
stimuli for AVP production include volume deple- Fluid and sodium restriction for oliguric states
tion; hypotension; edematous states such as con- Acute glomerulonephritis
gestive heart failure, cirrhosis, and the nephrotic Acute tubular necrosis
syndrome; and sepsis.13 Nonhemodynamic phys- End-stage renal disease
iological stimuli for AVP secretion include pain, Increased free-water requirements for renal concentrating defects
stress, nausea, vomiting, hypoxemia, hypercapnia, Congenital nephrogenic diabetes insipidus
hypoglycemia, and the perioperative state.12,14 Sickle cell disease
These physiological stimuli can result in in- Obstructive uropathy
creased AVP levels in the absence of volume de-
Reflux nephropathy
pletion or hyperosmolality.12 In addition, an ever-
Renal dysplasia
expanding list of conditions and medications is
Nephronophthisis
associated with the syndrome of inappropriate
Tubulointerstitial nephritis
antidiuresis, in which AVP excess occurs in the
Use of lithium
absence of any identifiable nonosmotic stimuli
Increased sodium and water requirements for solute diuresis
for AVP production.19 The conditions most often
Diuretic phase of acute tubular necrosis
associated with this syndrome are cancer, cen-
Postobstructive diuresis
tral nervous system (CNS) disorders, pulmonary
Immediate postoperative renal transplantation
disorders, and infections.19 Medications that are
frequently associated with this syndrome include Diabetic ketoacidosis
narcotics, the chemotherapeutic agents cyclophos- Bartter’s syndrome
phamide and vincristine, selective serotonin- Fanconi’s syndrome
reuptake inhibitors, the antiepileptic agent ox- Cerebral salt wasting
carbazepine, and the recreational drug “ecstasy” Adrenal insufficiency
(3,4-methylenedioxymethamphetamine [MDMA]). Increased free-water requirements for extrarenal free-water losses
Thiazide diuretics can also be associated with a Burns
condition that resembles the syndrome of inap- Prematurity in neonates
propriate antidiuresis. The syndrome of inappro- Fever
priate antidiuresis is now recognized as the most Infectious diarrhea
common cause of euvolemic hyponatremia.20

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 The n e w e ng l a n d j o u r na l of m e dic i n e

liter, is the most common electrolyte abnormal-

Hemodynamic stimuli Nonhemodynamic stimuli ity in hospitalized patients; it affects approxi-
mately 15 to 30% of children and adults who are
Volume depletion Pain and stress hospitalized.22,23 Most hyponatremia in these
patients is hospital-acquired and is related to the
Hypotension Nausea and vomiting administration of hypotonic intravenous fluids
in patients with elevated AVP levels.16,23-26 Virtu-
Congestive heart failure Hypoxemia and hypercapnia ally all studies evaluating hospital-acquired hypo-
natremia have shown that it is related to the
Cirrhosis Hypoglycemia administration of hypotonic fluids.23,24,27-30
The most serious complication of hospital-
Nephrotic syndrome Medications acquired hyponatremia is hyponatremic enceph-
alopathy, which is a medical emergency that can
Adrenal insufficiency Perioperative state
be fatal or lead to irreversible brain injury if it is
inadequately treated.7,10 All large studies of hos-
pital-acquired hyponatremic encephalopathy have
Inflammation
involved primarily otherwise healthy children
and adults who were receiving hypotonic fluids;
Cancer
in many cases, this condition followed minor
surgical procedures.7,8,10,11,31 The strong associa-
Pulmonary disease
tion between the use of hypotonic fluid and
hyponatremic encephalopathy and the number of
CNS disease preventable deaths in children that have resulted
from the use of hypotonic fluid have drawn the
Figure 1. Nonosmotic States of Arginine Vasopressin (AVP) Excess. attention of the National Patient Safety Agency
Numerous hemodynamic and nonhemodynamic stimuli for AVP secretion in the United Kingdom32 and the Institute for
place virtually all acutely ill hospitalized patients at risk for the development Safe Medication Practices of Canada33 and the
of hyponatremia. Physiological stimuli can result in an increase in AVP levels United States.34,35 All three organizations have
in the absence of volume depletion or hyperosmolality. In numerous disease
issued warnings about the dangers of adminis-
states and medications associated with the syndrome of inappropriate anti-
diuresis, AVP excess occurs in the absence of any identifiable nonosmotic tering hypotonic fluids in children and have
stimuli for AVP production.12-14 called for the establishment of and adherence to
guidelines for administration of fluid. Similar
patient-safety warnings have not, however, been
The ability to produce concentrated urine de- issued for adults.
pends on both the ability to maintain a concen- Patients with hospital-acquired hyponatremia
trated renal medullary interstitium and the wa- are at particular risk for the development of hypo-
ter permeability of the collecting duct in response natremic encephalopathy, which usually devel-
to AVP. Diseases or medications that disrupt the ops acutely, in less than 48 hours, leaving little
medullary interstitium or interfere with the ac- time for brain adaptation. Hospitalized patients
tion of AVP will result in a renal concentrating who are at particular risk for the development
defect and can lead to hypernatremia in patients of hyponatremic encephalopathy at even mildly
with restricted access to free water (Table 1).21 hyponatremic levels include children younger
Common reasons for a renal concentrating de- than 16 years of age,8 women in their reproduc-
fect include tubulointerstitial renal diseases such tive years,7 and patients with hypoxemia36 or
as obstructive uropathy and sickle cell disease, underlying CNS disease,37 since these conditions
genetic disorders such as congenital nephro- either impair regulation of brain-cell volume or
genic diabetes insipidus, and the use of lithium. are associated with decreased intracranial capac-
ity for brain expansion (Table 2).
Prevention of hospital-acquired hyponatremic
Hospital-Acquir ed Hyponatr emia
encephalopathy is critical, since the presenting
Hyponatremia, which is defined as a plasma symptoms are nonspecific and can be easily
sodium concentration of less than 135 mmol per overlooked until advanced symptoms develop.

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 Maintenance Fluids in Acutely Ill Patients

The most consistent symptoms of hyponatremic Table 2. Risk Factors for Hyponatremic Encephalopathy.
encephalopathy are headache, nausea, vomiting,
and generalized weakness.7,38,39 Advanced symp- Risk Factor Pathophysiological Mechanism
toms of hyponatremic encephalopathy include Acute hyponatremia Decreased time for brain adaptation
seizures, respiratory arrest, noncardiogenic pul- (<48 hr)
monary edema, and decorticate posturing.7,38,39 Age <16 yr Increased ratio of brain to intracranial volume
Symptoms can occur abruptly and do not always Female sex Sex steroids (estrogens) inhibit brain adaptation
correlate with the plasma sodium concentration Increased AVP levels
or the rapidity of development of hyponatre- Cerebral vasoconstriction
Hypoperfusion of brain tissue
mia.7,10,38,40
Hypoxemia Impaired brain adaptation
Failure to recognize and treat hyponatremic Decreased cerebral perfusion
encephalopathy with hypertonic saline results in
Brain injury Vasogenic cerebral edema
a poor neurologic prognosis.7,10 Fluid restriction Cytotoxic cerebral edema
alone, isotonic fluids, and vaptans have no role
in the immediate management of hyponatremic
encephalopathy.14,39 as either of the following: 1500 ml per 1.73 m2 of
Mounting data show that even chronic hypona- body-surface area per 24 hours or, as calculated
tremia, which develops over a period of 48 hours with the use of the Holliday–Segar formula, 100 ml
or longer, without apparent neurologic symp- per kilogram per 24 hours for the first 10 kg
toms, is deleterious. Chronic hyponatremia has of body weight, plus 50 ml per kilogram per
been shown to result in subtle neurologic im- 24 hours for a weight of greater than 10 to 20 kg,
pairment, which can cause gait disturbances and an additional 20 ml per kilogram per 24 hours
that lead to falls and associated bone fractures for a weight above 20 kg.6,52
in the elderly, with increased bone fragility re- Such recommendations are based on theoreti-
sulting from bone demineralization.41-45 cal calculations from the 1950s, before the syn-
Hyponatremia is an independent risk factor drome of inappropriate antidiuresis was recog-
for death in the hospital setting, particularly nized as a common clinical entity. In 1953,
among patients with end-stage liver disease, Talbot et al. made recommendations regarding
congestive heart failure, pneumonia, and end- the administration of fluids in adults according
stage renal disease, and it is associated with to a theoretical model of the maximal and
increased hospital costs, length of hospital stay, minimal amount of sodium and water in paren-
and rates of readmission.46-50 When hyponatre- teral fluids that could be administered without
mia develops, it can be difficult to correct, since adverse effects.53 In 1957, Holliday and Segar
most initial therapies, such as fluid restriction made similar recommendations for children ac-
and isotonic fluids, are relatively ineffective in cording to average caloric requirements for hos-
correcting euvolemic and hypervolemic hypona- pitalized children and electrolyte requirements
tremia.20 For all these reasons, strategies should based on dietary intake.52 However, these recom-
be implemented to prevent hyponatremia. mendations lack validation in clinical practice in
children or adults. All current recommendations
regarding the composition and rate of mainte-
C oncer ns a bou t H y p o t onic
M a in tena nce Fluids in nance fluid therapy in children and adults, regard-
Chil dr en a nd A dult s less of the patient’s condition, are predominantly
opinion-based.51
Hypotonic fluids continue to be recommended We previously suggested that isotonic fluids
as maintenance fluids in acutely ill patients de- should be administered in maintenance intrave-
spite the strong association between their use nous fluids to prevent hospital-acquired hypo-
and the development of hospital-acquired hypo- natremia in acutely ill children and that the
natremia.6,51 The prevailing practice has been to routine practice of administering hypotonic fluids
administer hypotonic fluids (e.g., 5% dextrose in (sodium concentration, <130 mmol per liter) be
a solution of 0.18 to 0.45% saline) at a rate of abandoned because of the increased risk of hypo-
approximately 2.0 to 3.0 liters per day in adults. natremia.54 We subsequently extended this rec-
The equivalent amount in children is estimated ommendation to apply to adult patients.16

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Currently, to our knowledge, there are no overload with edema or hypertension, and hy-
formal society-sponsored guidelines for mainte- perchloremic acidosis.60
nance fluid therapy in hospitalized patients in More than 15 randomized, prospective trials
the United States. Attempts have been made to involving more than 2000 patients have evalu-
develop consensus guidelines for children and ated the safety and efficacy of isotonic fluids as
adults in the United Kingdom.6,32,55,56 compared with hypotonic fluids for the preven-
The first consensus guideline on fluid ther- tion of hyponatremia.61-66 Most of these studies
apy was issued by the U.K. National Health involved children, the majority of whom were
Service in 2007. The National Health Service is- surgical and critical care patients. Isotonic flu-
sued a patient-safety alert to remove 0.18% sa- ids were superior to hypotonic fluids for the
line from general-use areas (e.g., the emergency prevention of hyponatremia in all but 1 small
department and pediatric ward) for children and study,67 in which 37 patients were followed for
recommended 0.45% saline for maintenance approximately 12 hours. Isotonic fluids were not
fluids for the majority of children and 0.9% sa- associated with an increased risk of hypernatre-
line for children at high risk for hyponatremia.32 mia or fluid overload, and there were no appar-
These opinion-based recommendations were sub- ent serious complications. A meta-analysis of 10
sequently adopted for the care of children in of these studies, involving almost 1000 children,
Northern Ireland by the Regulation and Quality showed that hypotonic fluids were associated
Improvement Authority and in Australia by the with a relative risk of 2.37 for the development
Victorian Paediatric Clinical Network. Prelimi- of mild hyponatremia (sodium concentration,
nary data suggest that these recommendations <135 mmol per liter) and a relative risk of 6.2 for
may have been helpful in reducing the incidence the development of moderate hyponatremia (so-
of hyponatremia.57 dium concentration, <130 mmol per liter).61
Even though 0.18% saline was essentially Some physicians have argued that fluid restric-
banned throughout the United Kingdom for use tion with hypotonic fluids would be sufficient to
in children, consensus guidelines still recom- prevent hyponatremia.58 In 4 studies, fluid re-
mend it as a maintenance fluid in adults.6,55 The striction with hypotonic fluids was not effective
British Consensus Guidelines on Intravenous in preventing hyponatremia.68-71
Fluid Therapy for Adult Surgical Patients, which It has also been argued that isotonic fluids
were published in 2008 and updated in 2011, may not be necessary for the prevention of hypo-
recommend 0.18 to 0.45% saline for postopera- natremia in a general pediatric ward. A study
tive maintenance fluids.55 In 2013, the National involving almost 700 children showed that the
Institute for Health and Care Excellence guide- odds ratio for prevention of hyponatremia with
lines for intravenous fluid therapy in adults, an isotonic fluid was similar among surgical
which were published in the United Kingdom, patients and nonsurgical patients and among
recommended 0.18% saline for maintenance patients who were in intensive care and those
fluids.6 These guidelines were primarily opinion- who were not in intensive care.62
based and included low-quality evidence on which Taken together, these studies suggest that
to base recommendations. These consensus isotonic fluids are most appropriate for the vast
guidelines lack validation in clinical practice. majority of hospitalized patients who are at risk
for elevated AVP levels and hospital-acquired
hyponatremia. This does not mean that isotonic
Iso t onic M a in tena nce Fluids
for the Pr e v en t ion of Hospi ta l - fluids are appropriate in all clinical settings or
Ac quir ed H y p onat r emi a that they are without risk. The studies were of
short duration (usually <72 hours) and excluded
The use of isotonic fluids in maintenance fluids patients with renal disease, heart failure, and
for the prevention of hospital-acquired hypona- cirrhosis. Precautions were taken if complica-
tremia in acutely ill patients was initially contro- tions were developing. It is not certain whether
versial,58,59 owing mainly to the potential for the side-effect profile with isotonic fluids would
unintended consequences. These consequences be as favorable in other patient populations,
include the development of hypernatremia, fluid such as the elderly, as it is in children.

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 Maintenance Fluids in Acutely Ill Patients

Isotonic fluids may result in hyponatremia in is perfectly matched with plasma (Table 3).
patients with CNS injury in whom cerebral salt Multiple electrolytes injection, type 1, USP, (an
wasting develops or in patients with the syn- infusion fluid) has a supraphysiologic buffer con-
drome of inappropriate antidiuresis in whom the centration of 50 mmol per liter. Ringer’s lactate
urine osmolality is greater than 500 mOsm per contains calcium and may be incompatible with
kilogram.72 Isotonic fluids could also result in blood products and some medications. There are
hypernatremia if there is a renal concentrating insufficient data to suggest that 0.9% saline is
defect or if there are large extrarenal free-water unsafe when used as a maintenance fluid.
losses. Any type of intravenous fluid can result
in fluid overload if administered in excessive Selecting the Rate of Administration
quantities (for example, in patients with end- and the Composition of Maintenance
stage renal disease or heart failure in whom Intravenous Fluids
both sodium excretion and water excretion are No single rate of administration or composition
impaired). In most circumstances, the adminis- of maintenance intravenous fluids is appropriate
tration of isotonic fluids should not lead to hyper- in all circumstances. Thus, intravenous fluids
natremia or fluid overload.73 may be viewed as medications that require care-
ful dose adjustment that is specific to the dis-
Balanced Salt Solutions as Compared ease state of each patient.
with 0.9% Saline The rate of administration and the composi-
An area of active investigation focuses on the tion of intravenous fluids need to be individual-
potential for deleterious effects associated with ized, and while patients are receiving intrave-
0.9% saline (normal saline) as compared with nous fluids, they require close monitoring with
those associated with balanced electrolyte solu- daily measurement of weight, frequent assessment
tions (Table 3).17,74 Normal saline (sodium con- of vital signs, strict measurements of intake and
centration, 154 mmol per liter) has the same output, and daily measurement of serum electro-
sodium concentration as the aqueous phase of lyte levels and physical examination. Many chil-
human plasma, but it has a supraphysiologic dren have died of hyponatremic encephalopathy
chloride concentration. Saline solutions may also within 24 hours after the initiation of hypotonic
have a pH that is far lower than that of water intravenous fluids, so even close observation may
(range, 3.5 to 7.0). The low pH of 0.9% saline be inadequate to prevent this complication.
appears to be related to the polyvinyl chloride Table 1 lists a broad range of conditions that
bags in which it is packaged, since the pH of require special consideration when maintenance
0.9% saline in a glass bottle is 7.0. fluid therapy is administered, and Figure 2
Deleterious consequences of 0.9% saline have shows a practical approach for adjusting mainte-
been associated primarily with studies (both in nance intravenous fluids according to these con-
animals and in humans) in which infusion is ditions. This approach is opinion-based, since
rapid and with clinical scenarios in which fluid data are lacking from studies evaluating the most
resuscitation or intraoperative fluid management appropriate fluid therapy for all conditions.
includes administration of a large volume of Dextrose is provided in maintenance fluids to
fluid.74 In such circumstances, 0.9% saline, as provide sufficient calories to prevent hypoglyce-
compared with balanced salt solutions, may pro- mia and limit tissue catabolism, but it does not
duce a hyperchloremic metabolic acidosis, re- provide complete nutritional support. Some dex-
nal vasoconstriction, delayed micturition, an in- trose-containing saline solutions are hyperosmo-
creased incidence of acute kidney injury requiring lar to plasma, but they are not hypertonic, since
renal-replacement therapy, and hyperkalemia. the dextrose is rapidly metabolized on entering
Whether any of these complications will oc- the bloodstream (Table 3). The default mainte-
cur when 0.9% saline is used at maintenance nance solution for adults is 5% dextrose in a
rates for less than 72 hours is unclear, but ran- solution of 0.9% saline administered at a rate of
domized trials that have been sufficiently pow- 100 to 120 ml per hour; this is based on the fact
ered to assess this possibility have not been con- that most hospitalized patients are at risk for
ducted. Currently, no balanced electrolyte solution euvolemic hyponatremia from AVP excess if they

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 1356
Table 3. Composition of Commercially Available Intravenous Crystalloid Solutions for Fluid Therapy.*

Electrolyte-free
Fluid Glucose Sodium Chloride Potassium Buffer† Calcium Magnesium pH Osmolarity Osmolality Water

mOsm/ mOsm/
g/dl millimoles per liter liter kg %‡
Human plasma 0.07–0.11 135–144 95–105 3.5–5.3 23–30 2.2–2.6 0.8–1.2 7.35–7.45 308 288 0
5% Dextrose in water 5 0 0 0 0 0 0 3.5–6.5 252 100
4% Dextrose in 0.18% sa- 4 30 30 0 0 0 0 3.5–6.5 282 81
line
5% Dextrose in 0.2% saline 5 34 34 0 0 0 0 3.5–6.5 321 78
5% Dextrose in 0.45% sa- 5 77 77 0 0 0 0 3.5–6.5 406 50
The

line
5% Dextrose Ringer’s lac- 5 130 109 4 28 1.5 0 4.0–6.5 525 13
tate
5% Dextrose in 0.9% saline 5 154 154 0 0 0 0 3.5–6.5 560 0
5% Dextrose multiple elec- 5 140 98 5 50 0 1.5 4.0–6.5 547 6
trolytes injection, type 1,
USP
Ringer’s lactate 0 130 109 4 28 1.35 0 6–7.5 273 254 13
Ringer’s acetate 0 130 112 5 27 1 1 6–8 276 12
Hartmann’s solution 0 131 111 5 29 2 0 5.0–7.0 278 12
n e w e ng l a n d j o u r na l

0.9% Saline 0 154 154 0 0 0 0 4.5–7 308 286 0

The New England Journal of Medicine

of

Multiple electrolytes injec- 0 140 98 5 50 0 1.5 4.0–6.5 294 6

tion, type 1, USP§
Isotonic electrolyte solu- 0 140 127 4 29 2.5 1 4.6–5.4 304 6

n engl j med 373;14 nejm.org  October 1, 2015

tion¶

Copyright © 2015 Massachusetts Medical Society. All rights reserved.

m e dic i n e

* To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for potassium to milligrams per deciliter, divide by 0.2558. To convert the values for
calcium to milligrams per deciliter, divide by 0.250. To convert the values for magnesium to milligrams per deciliter, divide by 0.4114. USP denotes United States Pharmacopeia.
† The buffer is bicarbonate in plasma, lactate in Ringer’s lactate and Hartmann’s solution, acetate in Ringer’s acetate, acetate (27 mmol per liter) and gluconate (23 mmol per liter) in
multiple electrolytes injection, type 1, USP, and acetate (23 mmol per liter) and maleate (5 mmol per liter) in isotonic electrolyte solution.
‡ This percentage is based on a sodium plus potassium concentration in the aqueous phase of plasma of 154 mmol per liter, assuming that plasma is 93% water with a plasma sodium

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concentration of 140 mmol per liter and a potassium concentration of 4 mmol per liter.
§ Multiple electrolytes injection, type 1, USP, is the generic name for Plasma-Lyte 148, Normosol, and Isolyte.
¶ Isotonic electrolyte solution is the generic name for Sterofundin and Ringerfundin. It has an electrolyte composition that is similar to that of plasma.
 Maintenance Fluids in Acutely Ill Patients

Assess for signs of extracellular volume depletion or hypoperfusion

(hypotension, tachycardia, delayed capillary refill, decreased peripheral pulses)

If yes: administer bolus with 500–1000 ml (adults) or 20 ml/kg (children) of isotonic

crystalloid and repeat as needed until adequate peripheral perfusion reestablished

Assess for disorders in renal concentration or dilution

Euvolemic states Renal concentrating

Oligoanuric states Edematous states CNS disease
of AVP excess defects

5% dextrose in isotonic 5% dextrose in isotonic 5% dextrose in isotonic 5% dextrose in isotonic 5% dextrose in isotonic
solution solution solution solution (may need to be solution (may need to be
25 ml/hr (adults) 40–60 ml/hr (adults) ≤100–120 ml/hr (adults) adjusted to hypertonic adjusted to hypotonic
25% of amount calculated 40–60% of amount calcu- ≤100% of amount calcu- fluid to maintain plasma fluid)
with Holliday–Segar lated with Holliday– lated with Holliday– sodium level >140 mmol/ ≥120 ml/hr (adults)
formula (children) Segar formula (children) Segar formula (children) liter) ≥120% of amount cal-
100–120 ml/hr (adults) culated with Holliday–
100% of amount calcu- Segar formula
lated with Holliday– (children)
Segar formula (children)

Figure 2. Guide to Maintenance Intravenous Fluid Therapy in Acutely Ill Patients.

Since most hospitalized patients are at risk for hyponatremia from AVP excess, in most acutely ill adults, the safest type of maintenance
solution and rate of administration are 5% dextrose in a solution of 0.9% saline at a rate of 100 to 120 ml per hour. In children, the equiva-
lent dose is either 1500 ml per 1.73 m2 of body-surface area per 24 hours or an amount calculated with the use of the Holliday–Segar
formula (100 ml per kilogram per 24 hours for the first 10 kg of body weight, plus 50 ml per kilogram per 24 hours for weight greater
than 10 to 20 kg, and an additional 20 ml per kilogram per 24 hours for weight above 20 kg). The rate and composition of intravenous
fluids will need to be adjusted for certain conditions. Patients at risk for fluid overload require fluid restriction. Patients with clinically
significant renal concentrating defects require an increased volume of hypotonic fluids to keep up with ongoing urinary free-water losses.
Hypotonic fluids should be administered only if there is a specific indication, and they should be avoided if hyponatremia is present. In
patients with central nervous system (CNS) diseases who are at risk for cerebral edema, the plasma sodium concentration should be
maintained at greater than 140 mmol per liter to prevent cytotoxic cerebral edema.

receive hypotonic fluids. Provision of fluids at a ly addressed in this review article or in the algo-
rate greater than or less than this amount is rithm in Figure 2. A common practice is to add
determined according to whether there is a dis- 20 mmol per liter of potassium to maintenance
order in renal concentration or a fluid overload intravenous fluids, but data to support the safety
state, respectively. A hypotonic fluid may be re- of this approach are lacking, and it is not clear
quired if there is a clinically significant renal that adding more than a physiologic concentra-
concentrating defect with ongoing free-water tion of potassium (i.e., >5 mmol per liter) is nec-
losses or to aid in the correction of established essary when intravenous fluids are administered
hypernatremia.4 for less than 48 hours, unless hypokalemia or
Studies that evaluate the most appropriate malnutrition is present or diuretics are being used.
maintenance fluid for edematous states are lack-
ing. It is our opinion that an isotonic fluid ad- Sum m a r y
ministered at a restricted rate would be appro-
priate, since these patients frequently have The administration of intravenous fluids is an
hyponatremia. essential component of supportive care for
Administration of potassium is not specifical­ acutely ill patients. Because of limited evidence,

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Box 1. Case 1.

Case 1 illustrates the use of perioperative maintenance therapy.

A 28-year-old woman who weighs 65 kg is admitted through the emergency department with a diagnosis of acute
­appendicitis. Given a history of poor oral intake, she receives a 1-liter bolus of 0.9% saline in the emergency department.
Vital signs and serum electrolyte levels are otherwise normal at presentation. What type and rate of maintenance intra-
venous fluid would you administer while the patient is receiving nothing by mouth both before surgery and postopera-
tively?
Answer: An appropriate fluid would be 5% dextrose in a solution of 0.9% saline at a rate of 100 ml per hour. Periop-
eratively, patients have numerous stimuli for AVP production, including pain, stress, nausea, narcotics administered for
pain management, and hypovolemia. In addition, women in their reproductive years are at increased risk for hypona-
tremic encephalopathy.7 Administration of 0.9% saline is suitable to maintain the extracellular volume and will reduce
the risk of hospital-acquired hyponatremia.

Box 2. Case 2.

Case 2 illustrates maintenance therapy in a patient with CNS disease.

A 75-year-old man who weighs 80 kg presents to the emergency department with symptoms consistent with a stroke.
A severe headache develops, followed by confusion and hemiparesis on his left side. He has a long-standing history of
hypertension treated with an angiotensin-converting–enzyme (ACE) inhibitor. On examination, he appears euvolemic,
with an elevated blood pressure of 150/100 mm Hg and normal serum electrolyte levels. What type and rate of mainte-
nance intravenous fluid would you administer while the patient is receiving nothing by mouth before evaluation and
management of a possible stroke?
Answer: An appropriate fluid would be 5% dextrose in a solution of 0.9% saline at a rate of 100 ml per hour. This pa-
tient appears to have an acute intracranial process suggestive of a stroke. He is at risk for increased intracranial pressure
and cerebral edema. Patients with CNS processes are at high risk for hyponatremia due to the syndrome of inappropri-
ate antidiuresis or cerebral salt wasting. In addition, hyponatremia can have extremely serious consequences in patients
with CNS disease, since a small decrease in the serum sodium concentration could result in cytotoxic cerebral edema,
thus aggravating vasogenic cerebral edema, which probably is already present.75 Administration of 0.9% saline would
help to prevent the development of hyponatremia, but the patient’s electrolyte levels would need to be monitored close-
ly, since the plasma sodium concentration can decrease in patients with CNS disease who receive 0.9% saline.72 The ad-
dition of 3% saline may be necessary to maintain a serum sodium concentration above 140 mmol per liter.

Box 3. Case 3.

Case 3 illustrates maintenance therapy in a patient with congestive heart failure.

An 87-year-old man who weighs 70 kg and who has a left-lower-lobe pneumonia is admitted to the hospital from a
nursing home. He has a history of myocardial infarctions and well-controlled congestive heart failure managed with an
ACE inhibitor, a beta-blocker, a thiazide diuretic, and a sodium-restricted diet. He received 500 ml of 0.9% saline during
transport to the hospital. His vital signs are stable, and there is no evidence of pulmonary congestion or peripheral ede-
ma on examination. Electrolyte levels are remarkable for a serum sodium concentration of 134 mmol per liter, potassium
3.2 mmol per liter, total carbon dioxide 31 mmol per liter, and creatinine 1.2 mg per deciliter (106 μmol per liter). Intra-
venous antibiotics are initiated. He is weak and has tachypnea and clinically significant coughing. There is a concern
that he is too ill to be able to drink sufficient fluids. What type and rate of maintenance intravenous fluid would you ad-
minister?
Answer: An appropriate fluid would be 5% dextrose in a solution of 0.9% saline plus 20 mmol potassium chloride
per liter at a rate of 60 ml per hour. This patient is at risk for both fluid overload and hyponatremia due to congestive
heart failure.76 Therefore, the rate of intravenous fluids should be restricted. A rate of 60 ml per hour or approximately
1.5 liters per day is probably adequate to maintain good peripheral perfusion without causing fluid overload. This pa-
tient has a low serum sodium concentration at 134 mmol per liter, so hypotonic fluids should not be administered. Re-
cent data suggest that sodium supplementation may be beneficial in patients with heart failure.77 Potassium should be
added to the intravenous fluids, since the patient has hypokalemia, probably from the thiazide diuretic and poor nutri-
tion. In this patient, the volume of intravenous medications needs to be accounted for, since it could contribute to both
fluid overload and hyponatremia.

recommendations regarding fluid have histori- Acutely ill patients have multiple stimuli for
cally been opinion-based. It has now become AVP that place them at risk for the development
clear that the administration of hypotonic main- of hyponatremia. Numerous prospective studies
tenance fluids (sodium concentration, <130 mmol involving children have shown that isotonic fluids
per liter) is associated with the development of are safe and effective in preventing hospital-
hospital-acquired hyponatremia as well as with acquired hyponatremia. Acutely ill patients can
deaths or permanent neurologic impairment have a variety of conditions that can alter body-
from hyponatremic encephalopathy. water homeostasis, so both the rate and the

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 Maintenance Fluids in Acutely Ill Patients

composition of intravenous fluid should be pre- lacking. A solid evidence base from which con-
scribed carefully. Isotonic fluids are the most sensus guidelines for fluid therapy could be
appropriate maintenance fluid in the vast major- built is also needed to better standardize fluid
ity of situations. In Box 1, Box 2, and Box 3, we management.
provide three practical cases regarding the most Drs. Moritz and Ayus report receiving consulting fees from
appropriate rate and composition of mainte- Otsuka and a continuing medical education honorarium from
the Global Education Group. No other potential conflict of in-
nance intravenous fluid. terest relevant to this article was reported.
Data from studies to determine whether bal- Disclosure forms provided by the authors are available with
anced solutions are superior to saline solutions the full text of this article at NEJM.org.
We thank Karen Branstetter for editing an earlier version of
for maintenance fluids and to determine the most the the manuscript and Kelli Crowly and Kevin Ordons for as-
appropriate potassium concentration in fluids are sistance in preparing an earlier version of Table 3.

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