Dengue is the most common arthropod-borne viral (Arboviral) illness in humans. Globally, 2.

5-3 billion individuals

live in approximately 112 countries that experience dengue transmission. Annually, approximately 50-100 million
individuals are infected. It is caused by infection with 1 of the 4 serotypes of dengue virus, which is a Flavivirus (a
genus of single-stranded nonsegmented RNA viruses). Infection with one dengue serotype confers lifelong
homotypic immunity to that serotype and a very brief period of partial heterotypic immunity to other serotypes,
but a person can eventually be infected by all 4 serotypes. Several serotypes can be in circulation during an
epidemic.
Dengue is transmitted by mosquitoes of the genus Aedes, which are widely distributed in subtropical and tropical
areas of the world (see the image below).
Initial dengue infection may be asymptomatic (50-90%),
[1]
may result in a nonspecific febrile illness, or may
produce the symptom complex of classic dengue fever (DF). Classic dengue fever is marked by rapid onset of high
fever, headache, retro-orbital pain, diffuse body pain (both muscle and bone), weakness, vomiting, sore throat,
altered taste sensation, and a centrifugal maculopapular rash, among other manifestations. The severity of the
pain led to the term breakbone fever to describe dengue.
A small percentage of persons who have previously been infected by one dengue serotype develop bleeding and
endothelial leak upon infection with another dengue serotype. This syndrome is termed dengue hemorrhagic fever
(DHF).
Dengue hemorrhagic fever has also been termed dengue vasculopathy. Vascular leakage in these patients results
in hemoconcentration and serous effusions and can lead to circulatory collapse. This, in conjunction with severe
hemorrhagic complications, can lead to dengue shock syndrome, which poses a greater fatality risk than bleeding
per se.
[2]

Dengue virus transmission follows 2 general patterns: epidemic dengue and hyperendemic dengue. Epidemic
dengue transmission occurs when dengue virus is introduced into a region as an isolated event that involves a
single viral strain. If the number of vectors and susceptible pediatric and adult hosts is sufficient, explosive
transmission can occur, with an infection incidence of 25-50%. Mosquito-control efforts, changes in weather, and
herd immunity contribute to the control of these epidemics. Transmission appears to begin in urban centers and
then spreads to the rest of the country.
[3]
This is the current pattern of transmission in parts of Africa and South
America, areas of Asia where the virus has reemerged, and small island nations. Travelers to these areas are at
increased risk of acquiring dengue during these periods of epidemic transmission.
Hyperendemic dengue transmission is characterized by the continuous circulation of multiple viral serotypes in an
area where a large pool of susceptible hosts and a competent vector (with or without seasonal variation) are
constantly present. This is the predominant pattern of global transmission. In areas of hyperendemic dengue,
antibody prevalence increases with age, and most adults are immune. Hyperendemic transmission appears to be a
major risk for dengue hemorrhagic fever. Travelers to these areas are more likely to be infected than are travelers
to areas that experience only epidemic transmission.
[4]

Because the signs and symptoms of dengue fever are nonspecific, attempting laboratory confirmation of dengue
infection by serodiagnosis, polymerase chain reaction (PCR), or culture is important. Serodiagnosis is made on the
basis of a rise in antibody titer in paired IgG or IgM specimens. Results vary depending on whether the infection is
primary or secondary (see Presentation and Workup). Dengue is a reportable disease in the United States; known
or suspected cases should be reported to public health authorities.
Dengue fever is usually a self-limited illness. Supportive care with analgesics, judicious fluid replacement, and bed
rest is usually sufficient. Successful management of severe dengue requires intravascular volume replacement,
with careful attention to fluid management and proactive treatment of hemorrhage. Admission to an intensive
care unit is indicated for patients with dengue shock syndrome (see Treatment).
Hosts for transmission
Humans serve as the primary reservoir for dengue. Certain nonhuman primates in Africa and Asia also serve as
hosts but do not develop dengue hemorrhagic fever. Mosquitoes acquire the virus when they feed on a carrier of
the virus. Persons with dengue viruses in their blood can transmit the viruses to the mosquito 1 day before the
onset of the febrile period. The patient can remain infectious for the next 6-7 days.
The mosquito can transmit dengue if it immediately bites another host. In addition, transmission occurs after 8-12
days of viral replication in the mosquito's salivary glands (extrinsic incubation period). The virus does not adversely
affect the mosquito. The mosquito remains infected for the remainder of its life. The life span of A aegypti is
usually 21 days but ranges from 15 to 65 days. Vertical transmission of dengue virus in mosquitoes has been
documented.
[10]
The eggs ofAedes mosquitoes withstand long periods of desiccation, reportedly as long as 1 year,
but are killed by temperatures of less than 10C. Rare cases of vertical dengue transmission have been reported. In
addition, rare reports of human-to-human transmission via needle-stick injuries have been published.
[11]

Once inoculated into a human host, dengue has an incubation period of 3-14 days (average 4-7 days) while viral
replication takes place in target dendritic cells. Infection of target cells, primarily those of the reticuloendothelial
system, such as dendritic cells, hepatocytes, and endothelial cells,
[12, 13, 14, 15]
result in the production of immune
mediators that serve to shape the quantity, type, and duration of cellular and humoral immune response to both
the initial and subsequent virus infections.
[12, 16, 17, 18, 19, 20, 21]

Dengue viral infections frequently are not apparent. In most cases, especially in children younger than 15 years,
the patient is asymptomatic or has a mild undifferentiated febrile illness lasting 5-7 days. Classic dengue fever
primarily occurs in nonimmune, nonindigenous adults and children and is typically self-limiting. Recovery is usually
complete by 7-10 days. Dengue hemorrhagic fever and dengue shock syndrome usually occur around the third to
seventh day of illness during a second dengue infection in persons with preexisting actively or passively
(maternally) acquired immunity to a heterologous dengue virus serotype.
Dengue fever
Dengue presents in a nonspecific manner similarly to that of many other viral and bacterial illnesses. Fever
typically begins on the third day of illness and persists 5-7 days, abating with the cessation of viremia. Fever may
reach 41C. Occasionally, and more frequently in children, the fever abates for a day and recurs, a pattern that is
termed a saddleback fever; however, this pattern is more commonly seen in dengue hemorrhagic fever.
Leukopenia, lymphopenia near the end of the febrile phase, and thrombocytopenia are common findings in
dengue fever and are believed to be caused by direct destructive actions of the virus on bone marrow precursor
cells. The resulting active viral replication and cellular destruction in the bone marrow are believed to cause the
bone pain. Approximately one third of patients with dengue fever may have mild hemorrhagic symptoms,
including petechiae, gingival bleeding, and a positive tourniquet test (>20 petechiae in an area of 2.5 X 2.5 cm).
Dengue fever is rarely fatal.
Dengue hemorrhagic fever
Dengue hemorrhagic fever occurs less frequently than dengue fever but has a more dramatic clinical presentation.
In most of Asia, where it first was described, dengue hemorrhagic fever is primarily a disease of children. However,
in the Americas, and more recently reported in Taiwan, dengue hemorrhagic fever has an equal distribution in all
ages.
Dengue hemorrhagic fever typically begins with the initial manifestations of dengue fever. The acute febrile illness
(temperatures 40C), like that of dengue fever, lasts approximately 2-7 days. However, in persons with dengue
hemorrhagic fever, the fever reappears, giving a biphasic or saddleback fever curve.
Along with biphasic fever, patients with dengue hemorrhagic fever have progressive thrombocytopenia, increasing
hematocrit (20% absolute rise from baseline) and low albumin (signs of hemoconcentration preceding shock),
more obvious hemorrhagic manifestations (>50% of patients have a positive tourniquet test), and progressive
effusions (pleural or peritoneal). Lymphocytosis, often with atypical lymphocytes, commonly develops before
defervescence or the onset of shock. Transaminase levels may be mildly elevated or present in the several
thousands associated with hepatomegaly in those patients with acute hepatitis. Low fibrinogen and elevated fibrin
split products are signs of disseminated intravascular coagulation. Severe metabolic acidosis and circulatory failure
can occur.
The critical feature of dengue hemorrhagic fever is plasma leakage. Plasma leakage is caused by increased capillary
permeability and may manifest as hemoconcentration, as well as pleural effusion and ascites. Bleeding is caused by
capillary fragility and thrombocytopenia and may manifest in various forms, ranging from petechial skin
hemorrhages to life-threatening gastrointestinal bleeding.
Liver damage manifests as increases in levels of alanine aminotransferase and aspartate aminotransferase, low
albumin levels, and deranged coagulation parameters (prothrombin time, partial thromboplastin time).
[22, 23]
In
persons with fatal dengue hepatitis, infection was demonstrated in more than 90% of hepatocytes and Kupffer
cells with minimal cytokine response (tumor necrosis factor [TNF]alpha, interleukin [IL]2). This is similar to that
seen with fatal yellow fever and Ebola infections.
[22]

As the term implies, dengue shock syndrome is essentially dengue hemorrhagic fever with progression into
circulatory failure, with ensuing hypotension, narrow pulse pressure (< 20 mm Hg), and, ultimately, shock and
death if left untreated. Death may occur 8-24 hours after onset of signs of circulatory failure. The most common
clinical findings in impending shock include hypothermia, abdominal pain, vomiting, and restlessness.
Secondary infection
The immunopathology of dengue hemorrhagic fever/dengue shock syndrome remains incompletely understood.
Most patients who develop dengue hemorrhagic fever or dengue shock syndrome have had prior infection with
one or more dengue serotypes. When an individual is infected with another serotype (ie, secondary infection) and
produces low levels of nonneutralizing antibodies, these antibodies, directed against 1 of 2 surface proteins
(precursor membrane protein and envelope protein), when bound by macrophage and monocyte Fc receptors,
have been proposed to fail to neutralize virus and instead form an antigen-antibody complex.
This results in increased viral entry into macrophages bearing IgG receptors, allowing unchecked viral replication
with higher viral titers and increased cytokine production and complement activation, a phenomenon called
antibody-dependent enhancement.
[24, 25]

The affected macrophages release vasoactive mediators that increase vascular permeability, leading to vascular
leakage, hypovolemia, and shock. This mechanism, along with individual host and viral genome variations, plays an
active role in pathogenesis. Infants born to mothers who have had dengue, as maternally derived dengue
neutralizing IgGs wane, are also thought to be at risk for enhanced disease.
[24, 25]

Some researchers suggest that T-cell immunopathology may play a role, with increased T-cell activation and
apoptosis. Increased concentrations of interferon have been recorded 1-2 days following fever onset during
symptomatic secondary dengue infections.
[26]
The activation of cytokines, including TNF-alpha, TNF receptors,
soluble CD8, and soluble IL-2 receptors, has been correlated with disease severity.
[12]

Cuban studies have shown that stored serum sample analysis demonstrated progressive loss of cross-reactive
neutralizing antibodies to DENV-2 as the interval since DENV-1 infection increased.
[19]
In addition, certain dengue
strains, particularly those of DENV-2, have been proposed to be more virulent, in part because more epidemics of
dengue hemorrhagic fever have been associated with DENV-2 than with the other serotypes.
Etiology
Dengue infection is caused by dengue virus (DENV), which is a single-stranded RNA virus (approximately 11
kilobases long) with an icosahedral nucleocapsid and covered by a lipid envelope. The virus is in the family
Flaviviridae, genus Flavivirus, and the type-specific virus is yellow fever.
The dengue virus has 4 related but antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. Genetic
studies of sylvatic strains suggest that the 4 serotypes evolved from a common ancestor in primate populations
approximately 1000 years ago and that all 4 separately emerged into a human urban transmission cycle 500 years
ago in either Asia or Africa.
[1, 27]
Albert Sabin speciated these viruses in 1944. Each serotype is known to have
several different genotypes. Viral genotype and serotype, and the sequence of infection with different serotypes,
appear to affect disease severity.
Living in endemic areas of the tropics (or warm, moist climates such as the southern United States) where the
vector mosquito thrives is an important risk factor for infection.
[8, 28, 29, 30, 31]
Poorly planned urbanization combined
with explosive global population growth brings the mosquito and the human host into close proximity. Increased
air travel easily transports infectious diseases between populations.
Prognosis
Dengue fever is typically a self-limiting disease with a mortality rate of less then 1%. When treated, dengue
hemorrhagic fever has a mortality rate of 2-5%. When left untreated, dengue hemorrhagic fever has a mortality
rate as high as 50%. Survivors usually recover without sequelae and develop immunity to the infecting serotype.
The fatality rate associated with dengue shock syndrome varies by country, from 12-44%. In a 1997 Cuban
epidemic, the fatality rate in patients who met criteria for dengue hemorrhagic fever or dengue shock syndrome
was approximately 6%. The mortality rate associated with dengue fever is less than 1%. Data from the 1997 Cuban
epidemic suggest that, for every clinically apparent case of dengue fever, 13.9 cases of dengue infection went
unrecognized because of absent or minimal symptoms.
A 2005 review from Singapore of 14,209 patients found that useful predictors of death included the following
[39]
:
Atypical presentations
Significant comorbid illness
Abnormal serum markers (including albumin and coagulation studies)
Secondary bacterial infections
Factors that affect disease severity include the following:
Patient age
Pregnancy
Nutritional status
Ethnicity
Sequence of infection with different dengue serotypes
Virus genotype
Quality and extent of available medical care
Complications and sequelae of dengue virus infections are rare but may include the following:
Cardiomyopathy
Seizures, encephalopathy, and viral encephalitis
Hepatic injury
Depression
Pneumonia
Iritis
Orchitis
Oophoritis
In 20-30% of dengue hemorrhagic fever cases, the patient develops shock, known as the dengue shock syndrome.
Worldwide, children younger than 15 years constitute 90% of dengue hemorrhagic fever patients
[34]
; however, in
the Americas, dengue hemorrhagic fever occurs in both adults and children.
Although dengue is an extremely important arboviral illness globally, literature evaluating the economic impact is
fairly sparse, with some conflicting findings. A recent expert panel assessment and 2 studies in the Americas
recommended additional research to fill important information gaps, including disease outcomes and accurate
statistics regarding disease burden, that could better inform future decision making regarding control and
prevention.
[40, 41, 42]

A 5-year prospective study in Thai children examined the relative economic burden of dengue infection in children
on the local population. Most disability-adjusted life years (DALYs) lost to dengue resulted from long-term illness in
children who had not been hospitalized. The infecting serotype appeared to be the major determinant of DALYs
lost, with DEN-2 and DEN-3 responsible for 59%. The mean cost of illness from dengue was significantly higher
than that from other febrile illnesses studied.
[38]

A prospective study examined the direct and indirect costs of dengue infection in 1695 pediatric and adult patients
in 8 countries. The average illness lasted 11.9 days for ambulatory patients and 11 days for hospitalized patients.
Hospitalized students lost 5.6 days of school. Those at work lost 9.9 work days. Overall mean costs were more than
double (1394 international dollars [I$]) for hospitalized cases. With an annual average of 594,000 cases the
aggregate economic cost was estimated to be at least I$587 million, without factoring in underreporting of disease
and dengue surveillance and vector control costs. This represents a significant global economic burden in low-
income countries.
[42]

Patient Education
Educate patients, especially those who have experienced prior dengue fever, to avoid mosquito bites, including the
use of appropriate mosquito repellants and peridomestic vector control, when traveling to dengue-endemic areas.
Current evidence suggests that those with a history of dengue fever are at highest risk for dengue hemorrhagic
fever or dengue shock syndrome if they are infected with a different dengue strain.
Information for reducing risk of contracting dengue while traveling, as well as current information on dengue
outbreaks, is available at the US Centers for Disease Control and Prevention Travel & Dengue Outbreaks Web page.
Information on dengue and alerts on current outbreaks are also available through the World Health
Organization Web site.
History
Patients with dengue will have a history of living in, or recent travel to, a region where the disease is endemic. The
incubation period is 3-14 days (average, 4-7 days); symptoms that begin more than 2 weeks after a person departs
from an endemic area are probably not due to dengue.
Many patients experience a prodrome of chills, erythematous mottling of the skin, and facial flushing (a sensitive
and specific indicator of dengue fever). The prodrome may last for 2-3 days. Children younger than 15 years usually
have a nonspecific febrile syndrome, which may be accompanied by a maculopapular rash. Classic dengue fever
begins with sudden onset of fever, chills, and severe (termed breakbone) aching of the head, back, and
extremities, as well as other symptoms. The fever lasts 2-7 days and may reach 41C. Fever that lasts longer than
10 days is probably not due to dengue.
Pain and other accompanying symptoms may include any of the following:
Headache
Retro-orbital pain
General body pain (arthralgias, myalgias)
Nausea and vomiting (however, diarrhea is rare)
Rash
Weakness
Altered taste sensation
Anorexia
Sore throat
Mild hemorrhagic manifestations (eg, petechiae, bleeding gums, epistaxis, menorrhagia, hematuria)
Lymphadenopathy
Rash in dengue fever is a maculopapular or macular confluent rash over the face, thorax, and flexor surfaces, with
islands of skin sparing. The rash typically begins on day 3 and persists 2-3 days.
Fever typically abates with the cessation of viremia. Occasionally, and more commonly in children, the fever abates
for a day and then returns, a pattern that has been called saddleback fever. A second rash may occur within 1-2
days of defervescence, lasting 1-5 days; it is morbilliform, is maculopapular, spares the palms and soles, and
occasionally desquamates.
Recovery is complete but slow, with fatigue and exhaustion often persisting after the fever has subsided. The
convalescent phase may last for 2 weeks.
Patients are at risk for development of dengue hemorrhagic fever or dengue shock syndrome at approximately the
time of defervescence. Abdominal pain in conjunction with restlessness, change in mental status, hypothermia,
and a drop in the platelet count presages the development of dengue hemorrhagic fever.
Of patients with dengue hemorrhagic fever, 90% are younger than 15 years. The initial phase of dengue
hemorrhagic fever is similar to that of dengue fever and other febrile viral illnesses. Shortly after the fever breaks
(or sometimes within 24 hours before), signs of plasma leakage appear, along with the development of
hemorrhagic symptoms such as bleeding from sites of trauma, gastrointestinal bleeding, and hematuria. Patients
may also present with abdominal pain, vomiting, febrile seizures (in children), and a decreased level of
consciousness.
If left untreated, dengue hemorrhagic fever most likely progresses to dengue shock syndrome. Common symptoms
in impending shock include abdominal pain, vomiting, and restlessness. Patients also may have symptoms related
to circulatory failure.
Physical Examination
Dengue fever presents in a nonspecific manner and may not be distinguishable from other viral or bacterial illness.
According to the Pan American Health Organization (PAHO), the clinical description of dengue fever is an acute
febrile illness of 2-7 days duration associated with 2 or more of the following:
Severe and generalized headache
Retro-orbital pain
Severe myalgias, especially of the lower back, arms, and legs
Arthralgias, usually of the knees and shoulders
Characteristic rash
Hemorrhagic manifestations
Leukopenia
Additional findings may include the following:
Injected conjunctivae
Facial flushing, a sensitive and specific predictor of dengue infection
Inflamed pharynx
Lymphadenopathy
Nausea and vomiting
Nonproductive cough
Tachycardia, bradycardia, and conduction defects
Up to half of patients with dengue fever develop a characteristic rash. The rash is variable and may be
maculopapular or macular. Petechiae and purpura may develop as hemorrhagic manifestations. Hemorrhagic
manifestations most commonly include petechiae and bleeding at venipuncture sites.
A tourniquet test is often positive. This test is performed by inflating a blood pressure cuff on the upper arm to
midway between diastolic and systolic blood pressures for 5 minutes. The results are considered to be positive if
more than 20 petechiae per square inch are observed on the skin in the area that was under pressure. Other
hemorrhagic manifestations include nasal or gingival bleeding, melena, hematemesis, and menorrhagia.
Neurologic manifestations such as seizures and encephalitis/encephalopathy have been reported in rare cases of
dengue infection. Some of these cases did not display other typical features of dengue infection. Other neurologic
complications associated with dengue infection include neuropathies, Guillain-Barr syndrome, and transverse
myelitis.
Dengue hemorrhagic fever
Findings for dengue hemorrhagic fever are similar to those for dengue fever and include the following:
Biphasic fever curve
Hemorrhagic findings more pronounced than in dengue fever
Signs of peritoneal effusion, pleural effusion, or both
Minimal criteria for the diagnosis of dengue hemorrhagic fever, according to the World Health Organization
(WHO), are as follows
[43]
:
Fever
Hemorrhagic manifestations (eg, hemoconcentration, thrombocytopenia, positive tourniquet test)
Circulatory failure, such as signs of vascular permeability (eg, hypoproteinemia, effusions)
Hepatomegaly
In addition, conjunctival injection develops in approximately one third of patients with dengue hemorrhagic fever.
Optic neuropathy has been reported and occasionally results in permanent and significant visual
impairment.
[44]
Pharyngeal injection develops in almost 97% of patients with dengue hemorrhagic fever.
Generalized lymphadenopathy is observed.
Hepatomegaly is present more often in dengue shock syndrome than in milder cases. Hepatic transaminase levels
may be mildly to moderately elevated. Encephalopathy is a rare complication that may result from a combination
of cerebral edema, intracranial hemorrhage, anoxia, hyponatremia, and hepatic injury.

Dengue shock syndrome
Findings of dengue shock syndrome include the following:
Hypotension
Bradycardia (paradoxical) or tachycardia associated with hypovolemic shock
Hepatomegaly
Hypothermia
Narrow pulse pressure (< 20 mm Hg)
Signs of decreased peripheral perfusion



Approach Considerations
Because the signs and symptoms of dengue fever are nonspecific, attempting laboratory confirmation of dengue
infection is important. Laboratory criteria for diagnosis include one or more of the following:
Isolation of the dengue virus from serum, plasma, leukocytes, or autopsy samples
Demonstration of a fourfold or greater change in reciprocal immunoglobulin G (IgG) or immunoglobulin M (IgM)
antibody titers to one or more dengue virus antigens in paired serum samples
Demonstration of dengue virus antigen in autopsy tissue via immunohistochemistry or immunofluorescence or in
serum samples via enzyme immunoassay (EIA)
Detection of viral genomic sequences in autopsy tissue, serum, or cerebral spinal fluid (CSF) samples via
polymerase chain reaction (PCR)
A reverse-transcriptase PCR test has demonstrated promise, yielding a serotype-specific diagnosis very rapidly.
[49,
50]
However, this test is currently available only in research laboratories.
The following laboratory tests should also be performed:
Complete blood count (CBC)
Metabolic panel
Serum protein and albumin levels
Liver panel
Disseminated intravascular coagulation (DIC) panel
Characteristic findings in dengue fever are thrombocytopenia (platelet count < 100 x 10
9
/L), leukopenia, and mild-
to-moderate elevation of aspartate aminotransferase and alanine aminotransferase values. Jaundice and acute
liver failure are uncommon. Peak liver enzyme levels occur later than other complications in adults studied
prospectively in Vietnam. Enzyme levels begin to rise during the early stage and peak during the second week.
Clinically severe involvement was found to be idiosyncratic and infrequent but did contribute to severe
bleeding.
[51]

A hematocrit level increase greater than 20% is a sign of hemoconcentration and precedes shock. The hematocrit
level should be monitored at least every 24 hours to facilitate early recognition of dengue hemorrhagic fever and
every 3-4 hours in severe cases of dengue hemorrhagic fever or dengue shock syndrome.
In patients with dengue hemorrhagic fever, the following may be present:
Increased hematocrit level secondary to plasma extravasation and/or third-space fluid loss
Hypoproteinemia
Prolonged prothrombin time
Prolonged activated partial thromboplastin time
Decreased fibrinogen
Increased amount of fibrin split products
Signs of early coagulopathy may be as subtle as a guaiac test that is positive for occult blood in the stool. Guaiac
testing should be performed on all patients in whom dengue virus infection is suspected.
Typing and crossmatching of blood should be performed in cases of severe dengue hemorrhagic fever or dengue
shock syndrome because blood products may be required.
Urinalysis identifies hematuria. Cultures of blood, urine, CSF, and other body fluids should be performed as
necessary to exclude or confirm other potential causes of the patient's condition.
Arterial blood gas should be assessed in patients with severe cases to assess pH, oxygenation, and ventilation.
Electrocardiography may demonstrate nonspecific changes as a result of fever, electrolyte disturbances,
tachycardia, or medications. The usefulness of these changes as a marker of cardiac involvement is unclear.
Biopsy of the skin lesions in patients with nonfatal, uncomplicated dengue fever reveals an abnormality of the
small blood vessels. Endothelial swelling, perivascular edema, and mononuclear cell infiltration are the primary
histologic findings.
Perform chest radiography to look for pleural effusions and bronchopneumonia. Right-sided pleural effusion is
typical. Bilateral pleural effusions are common in patients with dengue shock syndrome. Head computed
tomography without contrast may be indicated in patients with altered level of consciousness, to detect
intracranial bleeding or cerebral edema from dengue hemorrhagic fever.
Since January 2010, dengue has been a reportable illness in the United States. Report known or suspected cases of
dengue fever, dengue hemorrhagic fever, or dengue shock syndrome to public health authorities. Such reports
should include the following:
Patient demographics and recent travel history
Case classification
Date of onset of illness
Whether hospitalization was necessary
Outcome
When multiple patients are involved, reports should include the number of cases of dengue fever and dengue
hemorrhagic fever/dengue shock syndrome stratified by age, number of confirmed cases and serotypes, and
number of hospitalizations and deaths.
Complete Blood Cell Count
Leukopenia, often with lymphopenia, is observed near the end of the febrile phase of illness. Lymphocytosis, with
atypical lymphocytes, commonly develops before defervescence or shock. A systematic review found that patients
with dengue had significantly lower total WBC, neutrophil, and platelet counts than patients with other febrile
illnesses in dengue-endemic populations.
[52]

A hematocrit level increase greater than 20% is a sign of hemoconcentration and precedes shock. The hematocrit
level should be monitored at least every 24 hours to facilitate early recognition of dengue hemorrhagic fever and
every 3-4 hours in severe cases of dengue hemorrhagic fever or dengue shock syndrome.
Thrombocytopenia has been demonstrated in up to 50% of dengue fever cases. Platelet counts less than 100,000
cells/L are seen in dengue hemorrhagic fever or dengue shock syndrome and occur before defervescence and the
onset of shock. The platelet count should be monitored at least every 24 hours to facilitate early recognition of
dengue hemorrhagic fever.
Metabolic Panel and Liver Enzymes
Hyponatremia is the most common electrolyte abnormality in patients with dengue hemorrhagic fever or dengue
shock syndrome. Metabolic acidosis is observed in those with shock and must be corrected rapidly. Elevated blood
urea nitrogen (BUN) levels are observed in those with shock. Acute kidney injury is uncommon.
[53, 54]

Transaminase levels may be mildly elevated into the several thousands in patients with dengue hemorrhagic fever
who have acute hepatitis. Low albumin levels are a sign of hemoconcentration.
Coagulation Studies
Coagulation studies may help to guide therapy in patients with severe hemorrhagic manifestations. Findings are as
follows:
Prothrombin time is prolonged
Activated partial thromboplastin time is prolonged
Low fibrinogen and elevated fibrin degradation product levels are signs ofdisseminated intravascular coagulation
Serum Studies
Serum specimens should be sent to the laboratory for serodiagnosis, PCR, and viral isolation. Because the signs and
symptoms of dengue fever are nonspecific, attempting laboratory confirmation of dengue infection is important.
Serodiagnosis is made based on a rise in antibody titer in paired specimens obtained during the acute stage and
during convalescence. Results vary depending on whether the infection is primary or secondary.
The IgM capture enzyme-linked immunosorbent assay (MAC-ELISA) has become the most widely used serologic
assay for dengue. Other tests are also used, however, including the following:
Complement fixation (CF)
Neutralization test (NT)
Hemagglutination inhibition (HI)
IgG ELISA
NS1 strip test
[55]

Draw serum specimens for diagnosis as soon as possible after the onset of illness or hospitalization and at the time
of death or discharge from the hospital. Immediately place specimens on wet ice and send to the laboratory.
Obtain a second (ie, convalescent) blood sample for convalescent-phase serologic testing 7-21 days after the
acute-phase serum specimen was drawn. Ideally, draw the convalescent-phase serum specimen 10 days after the
acute-phase specimen.
A European study found that if only a single serum sample is available, a single positive result on enzyme-linked
ELISA (PanBio IgM or IgG) has a high rate of false positivity and should be confirmed using a second, more specific
diagnostic technique. In the absence of further testing, platelet and white blood cell counts can be diagnostically
helpful, because the combination of thrombocytopenia and leukopenia is present in 40.4% of confirmed cases but
in only 6.1% of false-positive cases.
[56, 57]

Ultrasonography
Ultrasonography is a potentially timely, cost-effective, and easily used modality in the evaluation of potential
dengue hemorrhagic fever. Positive and reliable ultrasonographic findings include fluid in the chest and abdominal
cavities, pericardial effusion, and a thickened gallbladder wall. Thickening of the gallbladder wall may presage
clinically significant vascular permeability.
[2, 58]

The utility of previous studies was limited because patients underwent only a single scan. However, in a study by
Srikiatkhachorn et al, daily serial ultrasonographic examinations of the thorax and abdomen proved useful in the
evaluation of patients with suspected dengue hemorrhagic fever.
[58]

Plasma leakage was detected in some patients within 3 days of fever onset. Pleural effusion was the most common
sign. Based on ultrasonographic findings, dengue hemorrhagic fever was predicted in 12 patients before
hemoconcentration criteria had been met.
Case Definitions
Cases are classified as suspected dengue if they are compatible with the clinical description. They are classified as
probable dengue if they are compatible with the clinical definition and satisfy one or more of the following criteria:
Supportive serology (reciprocal hemagglutination-inhibition antibody titer greater than 1280, comparable IgG EIA
titers, or positive IgM antibody test in late acute or convalescent-phase serum specimen)
Occurrence at the same location and time as other confirmed cases of dengue fever
A confirmed case of dengue is one that is compatible with the clinical definition and is confirmed by the laboratory.
Criteria for the diagnosis of dengue hemorrhagic fever include a probable or confirmed case of dengue infection
and hemorrhagic tendencies as evidenced by one or more of the following:
A positive result from the tourniquet test
Petechiae, ecchymoses, or purpura
Bleeding from the mucosa, gastrointestinal tract, injection sites, or other sites
Hematemesis or melena and thrombocytopenia (< 100,000 cells/L)
Evidence of plasma leakage due to increased vascular permeability
Plasma leakage may manifest as one or more of the following:
Greater than 20% rise in average hematocrit level for age and sex
Greater than 20% drop in hematocrit level following volume replacement compared with baseline
Signs of plasma leakage (eg, pleural effusion, ascites, hypoproteinemia)
Dengue shock syndrome is diagnosed in cases meeting all of the above criteria plus evidence of circulatory failure,
such as the following:
Rapid, weak pulse
Narrow pulse pressure (< 20 mm Hg), with increased peripheral vascular resistance (PVR) and elevated diastolic
pressure
Hypotension
Cool, clammy skin
Altered mental status, although the patient may initially remain alert
The onset of shock may be subtle, indicated by raised diastolic pressure and increased PVR in an alert patient.
WHO classification
The accuracy of the World Health Organization (WHO) classification system for dengue has been called into
question.
[59]
A study in Indonesian children found that the WHO classification system was in only modest
agreement with the intuitive classification by treating physicians, whereas several modified classification systems
were in good agreement.
[60]

The WHO classification system was found to have a sensitivity of 86% for the detection of dengue shock
syndrome.
[16]
Modified systems that added the above early predictors of compensated shock and considered
models using varying combinations of evidence of hemorrhagic tendencies, thrombocytopenia, and
hemoconcentration were found to yield higher sensitivities (88-99%).
Approach Considerations
Dengue fever is usually a self-limited illness. There is no specific antiviral treatment currently available for dengue
fever. The World Health Organization (WHO) has provided a number of free publications about dengue.
Supportive care with analgesics, fluid replacement, and bed rest is usually sufficient. Acetaminophen may be used
to treat fever and relieve other symptoms. Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and
corticosteroids should be avoided. Management of severe dengue requires careful attention to fluid management
and proactive treatment of hemorrhage.
Single-dose methylprednisolone showed no mortality benefit in the treatment of dengue shock syndrome in a
prospective, randomized, double-blind, placebo-controlled trial.
[61]
The Novartis Institute for Tropical Diseases
(NITD) in Singapore is carrying out research to find inhibitors of dengue viral target proteins to reduce the viral
load during active infection.
[62]

Suspected Dengue
Oral rehydration therapy is recommended for patients with moderate dehydration caused by high fever and
vomiting. Patients with known or suspected dengue fever should have their platelet count and hematocrit
measured daily from the third day of illness until 1-2 days after defervescence. Patients with clinical signs of
dehydration and patients with a rising hematocrit level or falling platelet count should have intravascular volume
deficits replaced under close observation. Those who improve can continue to be monitored in an outpatient
setting, and those who do not improve should be admitted to the hospital for continued hydration.
Patients who develop signs of dengue hemorrhagic fever warrant closer observation. Admission for intravenous
fluid administration is indicated for patients who develop signs of dehydration, such as the following:
Tachycardia
Prolonged capillary refill time
Cool or mottled skin
Diminished pulse amplitude
Altered mental status
Decreased urine output
Rising hematocrit
Narrowed pulse pressure
Hypotension
Severe Dengue
Successful management of severe dengue requires careful attention to fluid management and proactive treatment
of hemorrhage. Admission to an intensive care unit is indicated for patients with dengue shock syndrome.
Patients may need a central intravenous line for volume replacement and an arterial line for accurate blood
pressure monitoring and frequent blood tests. Exercise caution when placing intravascular catheters because of
the increased bleeding complications of dengue hemorrhagic fever. Urethral catheterization may be useful to
strictly monitor urine output.
Intravascular volume deficits should be corrected with isotonic fluids such as Ringer lactate solution. Boluses of 10-
20 mL/kg should be given over 20 minutes and may be repeated. If this fails to correct the deficit, the hematocrit
value should be determined. If it is rising, limited clinical information suggests that a plasma expander may be
administered. Starch, dextran 40, or albumin 5% at a dose of 10-20 mL/kg may be used. One study has suggested
that starch may be preferable because of hypersensitivity reactions to dextran.
[63]

If the patient does not improve after infusion of a plasma expander, blood loss should be considered. Patients with
internal or gastrointestinal bleeding may require transfusion, and patients with coagulopathy may require fresh
frozen plasma.
After patients with dehydration are stabilized, they usually require intravenous fluids for no more than 24-48
hours. Intravenous fluids should be stopped when the hematocrit falls below 40% and adequate intravascular
volume is present. At this time, patients reabsorb extravasated fluid and are at risk for volume overload if
intravenous fluids are continued. Do not interpret a falling hematocrit value in a clinically improving patient as a
sign of internal bleeding.
Platelet and fresh frozen plasma transfusions may be required to control severe bleeding. A case report
demonstrated good improvement following intravenous anti-D globulin administration in 2 patients. The authors
proposed that, as in immune thrombocytopenic purpura from disorders other than dengue, intravenous anti-D
produces Fc receptor blockade to raise platelet counts.
[64]

Patients who are resuscitated from shock rapidly recover. Patients with dengue hemorrhagic fever or dengue
shock syndrome may be discharged from the hospital when they meet the following criteria:
Afebrile for 24 hours without antipyretics
Good appetite, clinically improved condition
Adequate urine output
Stable hematocrit level
At least 48 hours since recovery from shock
No respiratory distress
Platelet count greater than 50,000 cells/L
Pregnant patients
Dengue in pregnancy must be carefully differentiated from preeclampsia. An overlap of signs and symptoms,
including thrombocytopenia, capillary leak, impaired liver function, ascites, and decreased urine output may make
this clinically challenging. Pregnant women with dengue fever respond well to the usual therapy of fluids, rest, and
antipyretics. However, 3 cases of maternal death due to dengue fever in the third trimester have been reported.
An awareness of the clinical and laboratory manifestations of dengue in pregnancy should allow its early
recognition and the institution of appropriate treatment. If the mother acquires infection in the peripartum period,
newborns should be evaluated for dengue with serial platelet counts and serological studies.
[65, 66]

Diet and Activity
No specific diet is necessary for patients with dengue fever. Patients who are able to tolerate oral fluids should be
encouraged to drink oral rehydration solution, fruit juice, or water to prevent dehydration from fever, lack of oral
intake, or vomiting. Return of appetite after dengue hemorrhagic fever or dengue shock syndrome is a sign of
recovery.
Bed rest is recommended for patients with symptomatic dengue fever, dengue hemorrhagic fever, or dengue
shock syndrome. Permit the patient to gradually resume their previous activities, especially during the long period
of convalescence.
Prevention
The only way to prevent dengue virus acquisition is to avoid being bitten by a vector mosquito. Although this can
be accomplished by avoiding travel to areas where dengue is endemic, that is not an ideal strategy because it
would require a person to avoid most tropical and subtropical regions of the world, many of which are popular
travel and work destinations. Other measures are as follows:
Wear N,N-diethyl-3-methylbenzamide (DEET)containing mosquito repellant
Wear protective clothing, preferably impregnated with permethrin insecticide
Remain in well-screened or air-conditioned places
The use of mosquito netting is of limited benefit, as Aedes are day-biting mosquitoes
Eliminate the mosquito vector using indoor sprays
The most widely used mosquito-control technique, spraying cities to kill adult mosquitoes, is not effective. Efforts
should target the larval phase with larvicides and cleaning up larvae habitats. Poor sanitation and poor refuse
control provide excellent conditions for mosquito larvae to grow. Hurricanes and other natural disasters increase
the habitat for mosquito growth in urban areas by increasing rubble and garbage, which act as water reservoirs.
Breeding of vector mosquitoes can be reduced by eliminating small accumulations of stagnant water around
human habitats (eg, disposing of old tires, covering water receptacles, and changing water in birdbaths daily.
Support community-based vector control programs (including source reduction) and the use of vectoricidal agents,
including predatory copepods as biological control agents.
[67, 68, 69, 70]

Outbreaks of dengue will increasingly cross common borders of endemic and disease-free countries unless the
following measures are undertaken:
Increased health surveillance
Prompt reporting of new cases
Heightened professional awareness
Public education
Vaccine Development
No vaccine is currently approved for the prevention of dengue infection. Because immunity to a single dengue
strain is the major risk factor for dengue hemorrhagic fever and dengue shock syndrome, a vaccine must provide
high levels of immunity to all 4 dengue strains to be clinically useful.
[71]

Immunogenic, safe tetravalent vaccines have been developed and are undergoing clinical trials.
[72]
Candidate
vaccines include a live-attenuated virus, recombinant envelope proteins, and an inactivated virus.
[73, 74, 75]
The
estimates of the time needed for further testing of candidate vaccines range from 5-10 years. Sanofi Pasteur has
reported successful results of phase II trials of its tetravalent recombinant live attenuated vaccine.
[76,
77]
Registration is anticipated in 2012.
Consultations
Consultation with an infectious diseases specialist may be helpful in guiding decisions regarding diagnosis and
treatment. Consultation with a critical care medicine specialist may be helpful when treating patients with dengue
hemorrhagic fever or dengue shock syndrome and severe hemorrhagic manifestations or shock.
Telephone consultation may be obtained from the Centers for Disease Control and Surveillance (800-232-4636,
8am-8pm ET/Monday-Friday).
Medication Summary
No specific antiviral medication is currently available to treat dengue. The treatment of dengue fever is
symptomatic and supportive in nature. Bed rest and mild analgesic-antipyretic therapy are often helpful in
relieving lethargy, malaise, and fever associated with the disease. Acetaminophen (paracetamol) is recommended
for treatment of pain and fever. Aspirin, other salicylates, and nonsteroidal anti-inflammatory drugs (NSAIDs)
should be avoided.
Patients with dengue hemorrhagic fever or dengue shock syndrome may require intravenous volume replacement.
Plasma volume expanders can be used in patients who do not respond to isotonic fluids.
Analgesics
Class Summary
These agents are used to reduce fever. They inhibit central synthesis and the release of prostaglandins that
mediate the effect of endogenous pyrogens in the hypothalamus and, thus, promote the return of the set-point
temperature to normal.
View full drug information
Acetaminophen (Tylenol, Feverall, Acephen, Mapap)

Acetaminophen (paracetamol) reduces fever by acting directly on hypothalamic heat-regulating centers, which
increases dissipation of body heat via vasodilation and sweating. It is used in dengue infections to relieve pain and
lower temperature when fever is thought to contribute to patient discomfort.
Crystalloids for Fluid Therapy
Class Summary
Isotonic (0.9%) sodium chloride solution or lactated Ringer solution is administered intravenously to maintain
intravascular volume, blood pressure, and urine output.
Lactated Ringer solution/isotonic sodium chloride solution

These fluids are used to expand intravascular volume. Both fluids are essentially isotonic and have equivalent
volume restorative properties. Although administration of large quantities of either fluid may lead to some
differences in metabolic changes, for practical purposes and in most situations, these differences are clinically
irrelevant. Importantly, no demonstrable difference in hemodynamic effect, morbidity, or mortality exists with
either product.
Volume Expanders
Class Summary
Plasma volume expanders are used in the treatment of intravascular volume deficits or shock to restore
intravascular volume, blood pressure, and tissue perfusion.
View full drug information
Dextran 40 (LMD)

Dextran 40 is a polymer of glucose. When infused, it increases intravascular volume, blood pressure, and capillary
perfusion. It is used to restore intravascular volume when isotonic crystalloid administration is inadequate for that
purpose.
View full drug information
Albumin (Albuminar-5, Buminate, Plasbumin 5)

Human albumin is a sterile solution of albumin, which is the major plasma protein responsible for the colloid
oncotic pressure of blood. It is pooled from blood, serum, plasma, or placenta from healthy donors. Infusion of
albumin results in a shift of fluid from the extracellular space into the bloodstream, thereby decreasing
hemoconcentration and blood viscosity.
Albumin may be administered wide open when treating shock. Patient response must be assessed before
repeating the dose.
View full drug information
Hetastarch (Hespan, Hextend)

Hydroxyethyl starch is a sterile solution of the starch responsible for the colloid oncotic pressure of blood.
Hetastarch produces volume expansion through its highly colloidal starch structure.
acetaminophen (OTC) - Tylenol, Tylenol Arthritis Pain, more..
Class: Analgesics, Othe
Adverse Effects
Frequency Not Defined
Angioedema
Disorientation
Dizziness
Pruritic maculopapular rash
Rash
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria
Gastrointestinal hemorrhage
Laryngeal edema
Agranulocytosis
Leukopenia
Neutropenia
Pancytopenia
Thrombocytopenia
Thrombocytopenic purpura
Hepatotoxicity
Liver failure
Nephrotoxicity
Pneumonitis
Anaphylactoid
Contraindications & Cautions
Contraindications
Hypersensitivity
Hepatitis or hepatic/renal dysfunction, alcoholism
Repeated administration in patients with anemia or cardiac, pulmonary, or renal disease
Cautions
Acetaminophen in many other dosage forms and products, check label carefully to avoid overdose
Risk of hepatotoxicity is higher in alcoholics, chronic high dose, or use of more than one acetaminophen-
containing product
G6PD deficiency
Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson
Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP)
Mechanism of Action
Acts on hypothalamus to produce antipyresis
May work peripherally to pain impulse generation; may also inhibit prostaglandin synthesis in CNS
Pharmacokinetics
Peak Plasma Time: 10-60 min (PO immediate-release); 60-120 min (PO extended-release); 6 hr (PO 500
mg, conventional tablet); 8 hr (PO 650 mg, extended-release tablet)
Peak Plasma Concentration: 2.1 mcg/mL (PO 500 mg, conventional tablet); 1.8 mcg/mL (PO 650 mg,
extended-release tablet)
Distribution: 1 L/kg
Protein Bound: 10 to 25%
Metabolism: Liver (microsomal enzyme systems); conjugation (glucuronic/sulfuric acid)
Metabolites: N-acetyl-p-benzoquinoneimine, N-acetylimidoquinone, NAPQI; further metabolized via
conjugation with glutathione
Half-life elimination: 1.25-3 hr
Excretion: urine (principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate)
dextran (Rx) - Gentran, LMD, more..
Class: Volume Expander
Shock
No more than 20 mL/kg IV during first 24 hours; THEN 10 mL/kg/day
Same mL dosage for both 10% & 6%
10% Solution
No more than 5 days
First 500 mL infused rapidly, then slow infusion
Surgery (DVT/PE Prophylaxis)
10% Solution: 500-1000 mL (~10 mL/kg) on day of surgery; THEN 500 mL/day for 2-3 days; THEN 500 mL q2-3Days
PRN up to 2 weeks
6% Solution: Not approved but used
Priming Fluid in Pump Oxygenators, Uterine Cavity Distention
Add 10-20 mL/kg (or 1-2 g/kg); not to exceed 20 mL/kg (2g/kg); dose varies with volume of pump oxygenator
Renal Impairment
Extreme caution
Hepatic Impairment
Extreme caution
Progenitor Cell Mobilization (Orphan)
Treatment to mobilze progenitor cells prior to stem cell transplantation
Orphan indication sponsor
TikoMed AB; P.O. Box 81 (Karlsfaltsvagen 349); SE-263 03, Viken, Sweden
Pancreatic Islet Transplantation (Orphan)
LMW dextran sulfate (Ibsolvmir): Prevention of graft rejection during pancreatic islet transplantation
Orphan indication sponsor
TikoMed AB; P.O. Box 81 (Karlsfaltsvagen 349); SE-263 03, Viken, Sweden
Adverse Effects
Frequency Not Defined
Congestive heart failure
Mild hypotension
Tightness of chest
Thrombocytopenia
Anaphylaxis
Injection site infection/phlebitis
Acute renal failure
Acidosis (if NaCl soln used)
Pulmonary edema
Wheezing
Contraindications
Hypersensitivity to dextran or corn products
Pulmonary edema, severe bleeding disorders, severe CHF, severe oliguria/anuria due to renal disease, significant
hemostatic defects, cardiac decompensation
10%: Marked thrombocytopenia or hypofibrinogenemia
Cautions
Decreased urinary output 2nd to shock, bowel surgery, dehydration, active hemorrhage, hypernatremia,
pathological abdominal conditions, thrombocytopenia
Monitor urinary output
Contains no preservatives, discard unused portions
Mechanism of Action
Branched polysaccharide volume expander through highly colloidal starch structure; lowers platelet & RBC
adhesiveness
Pharmacokinetics
Elimination half-life: 40 min
Duration: 3-4hr (plasma expanding effects)
Distribution half-life: 12 min
Vd: 6.5 L
Metabolism: Minimally in tissues; liver, kidney, spleen
Excretion: urine 75%
Dialyzable: HD: No
IV Incompatibilities
Do not dilute or admix with other drugs
IV Administration
Infuse first 500 mL over 15-30 min, then slow infusion
Storage
Protect from freezing
albumin IV (Rx) - Albuminar, Alba, more..
Class: Volume Expanders
Adverse Effects
Frequency Not Defined
Anaphylaxis
CHF precipitation
Edema
Hypertension/hypotension
Hypervolemia
Tachycardia
Decr myocardial contractility
Bronchospasm
Pulmonary edema
Salt and water retention
Chills
Fever
Headache
Nausea/vomiting
Pruritus
Rash
Urticaria
Contraindications
Hypersensitivity to commercially available albumin products
Severe anemia, cardiac failure
25% solution in preemies (risk of IVH)
Cautions
Chronic renal insufficiency, chronic anemia, low cardiac reserve, normal plasma albumin
Ineffective in chronic nephrosis or hypoproteinemia due to chronic cirrhosis, malabsorption, enteropathies,
pancreatic insufficiency or undernutrition
Do NOT use sterile water as diluent
All commercial formulations contain 130-160 mEq/L of sodium
Mechanism of Action
Replacement of plasma protein; increases intravascular oncotic pressure, mobilize fluids from interstitial into
intravascular space
Distribution
Plasma compartment: 30-40%
Extravascular compartments: 67%
Half-life, distribution: 16 hr; inversely proportional to plasma albumin concentrations
Metabolism
Minimally in the liver; main site is unknown
Elimination
Elimination half-life: 15-20 days
Excretion: Intestinal mucosa, not via kidney
IV Incompatibilities
Additive: Verapamil
Y-site: Fat emulsions, midazolam, vancomycin, verapamil
IV Compatibilities
Solution: Dextrose solutions, saline solutions, dextrose-saline, Ringer LR, Na-lactate 1/6M
Y-site: Diltiazem, lorazepam
IV Preparation
Reconstitution: If 5% human albumin is unavailable, dilute 25% human albumin with NS or D5W
Do NOT use sterile water as diluent - risk of potentially fatal hemolysis & ARF
IV Administration
For IV administration only
Use within 4 hr after opening vial; discard unused portion
Do not dilute 5% solution
Albumin 25% may be given undiluted or diluted in NS
May give in combination or through same administration set as saline or carbohydrates
Do not use with ethanol or protein hydrolysates; precipitation may form
Hypoproteinemia: Infuse over 30-120 min; not to exceed 5-10 mL/min for 5% solution, 2 mL/min for 20% solution,
and 2-3 mL/min for 25% solution
Hypovolemic shock
Initial bolus infusion as rapidly as desired
As plasma volume approaches normal, infuse 5% solution up to 2-4 mL/min and 25% solution up to 1 mL/min to
avoid circulatory overload
Storage
Store at <30C (86F); do not freeze
Do not use solution if turbid or contains a deposit; use within 4 hr of opening vial; discard unused portion
hetastarch (Rx) - Hespan, Hextend
Class: Volume Expanders
Adverse Effects
Frequency Not Defined
Anaphylaxis (periorbital edema, urticaria, wheezing, mild termperature elevation)
Chills
Flu-like symptoms
Myalgia
Peripheral edema
Headache
Pruritus
Vomitting
Salivary gland enlargement
Black Box Warnings
Do not use in critically ill adult patients including those with sepsis, and those admitted to the ICU
Avoid use in patients with pre-existing renal dysfunction
Discontinue use at the first sign of renal injury
Need for renal replacement therapy has been reported up to 90 days after administration; continue to monitor
renal function for at least 90 days in all patients
Avoid use in patients undergoing open heart surgery in association with cardiopulmonary bypass due to excess
bleeding
Discontinue at the first sign of coagulopathy
Contraindications
Hypersensitivity to hetastarch
Severe bleeding disorders, severe CHF, severe renal failure
Cautions
Allergy to corn, liver disease, renal impairment, thrombocytopenia
Risk of pulmonary edema or CHF
Potential for circulatory overload
Hetastarch in lactated solution contains potassium & sodium
Hextend not to be used in leukapheresis or lactic acidosis
Mechanism of Action
Ethoxylated amylopectins; colloidally expands plasma volume
Pharmacokinetics
Onset: 30 min
Duration: 6-36 hr
Half-life, Elimination: 17 days
Metabolism: Enzymatically degraded by reticuloendothelial system or amylases in blood
Excretion: Urine, feces (by biliary excretion)
IV Info
IV Incompatibilities
Y-site: (Lactated soln) amphotericin B, diazepam; (NS soln) amikacin, cefamandole, cefazolin(?), cefoperazone,
cefotaxime, cefoxitin, gentamicin, ranitidine, theophylline, tobramycin
IV Preparation
Do not use if crystalline precipitate forms or is turbid deep brown
IV Administration
Administer IV only
Infusion pump is required
May administer up to 1.2 g/kg/hr (20 mL/kg/hr)
Change IV tubing or flush copiously with NS before administering blood through same line
Change IV tubing at least every 24 hr
Do not administer Hextend with blood through same administration set
Anaphylactoid reactions can occur, have epinephrine & resuscitative equipment available
Storage
Store at room temperuature; do not freeze