Kwon KT, Tsai VW. Metabolic emergencies. Emerg Med Clin N Am. 2007;25:1041-1060.
In children, hypoglycemia = serum glucose < 40 - 45 mg/dL. In neonates within 1 day of life, levels as low as 30
mg/dL are considered by some to be normal.
• Adrenergic, due to activation of autonomic nervous system:
Usually seen early with a rapid decline in glucose
Tachycardia, tachypnea, vomiting, and diaphoresis
Most patients are hypoglycemic before ED arrival, so these symptoms are frequently absent
• Neuroglycopenic, due to decreased cerebral glucose:
Usually associated with slower or prolonged hypoglycemia
Poor feeding, altered mental status, lethargy, seizures
In infants, the presentation may be subtle: hypotonia, hypothermia, jitteriness, feeding difficulties.
Hypoglycemia occurring in children requiring resuscitation is associated with increased mortality.
4 mL/kg of 10% dextrose or 2 mL/kg of 25% dextrose (some advocate a smaller bolus of 2 mL/kg of 10% dextrose to
minimize hyperglycemia and resultant insulin secretion and possible prolonged hypoglycemia).
A 10% solution is used in neonates and infants, whereas a 25% solution is used in toddlers and children. More dilute
solutions are used in younger patients to minimize vascular injury caused by more concentrated fluids.
Continuous glucose infusion should follow bolus administration, especially in neonates. The normal glucose
requirement in a neonate is 6 - 10 mg/kg/min, which is roughly equivalent to an infusion of 10% dextrose-containing
solution at 1.5 times the maintenance rate.
If hypoglycemia persists despite boluses and infusions, a hyperinsulinemic state should be considered. Glucagon, 0.1
- 0.2 mg/kg (up to 1 mg) parenterally, can be given to infants for refractory hypoglycemia.
Glucagon will not be effective in patients lacking adequate glycogen stores, such as those with inherited storage
diseases. Hydrocortisone, 2 - 3 mg/kg can also be considered for refractory hypoglycemia.
Hyperglycemia and DKA
Hyperglycemia is frequently seen in the first week of life and is inversely correlated to gestational age, with a much
greater occurrence in neonates with birth weights < 1000 g.
Owing to their small mass of insulin-dependent tissue (i.e. muscle and fat), infants have limited glucose. The greatest
risk of hyperglycemia is dehydration secondary to the resulting urinary loss of glucose and osmotic diuresis.
Transient neonatal diabetes mellitus - resolves within weeks - months. Patients may have diabetes recur later in life.
The cause remains unclear, but immature metabolic pathways are suspected. Most patients have a low birth weight
for gestational age.
Recurrent cutaneous candidiasis, common in infants, but can be a sign of DM; an indication to check serum glucose.
DKA - defined as glucose > 200 mg/dL with HC03 < 15 mEq/L or a venous pH < 7.3.
DKA is more difficult to recognize and treat in younger patients: (1) The higher BMR and larger surface area to body
mass ratio in infants require stricter amounts of fluid and electrolyte repletion (2) The smaller patient is also at greater
risk for cerebral edema owing to the immaturity of autoregulatory mechanisms
Cerebral edema is the most likely cause of morbidity in DKA, with a mortality rate of 20% - 25% and pituitary
insufficiency in 10% - 25% of survivors.
Pathophysiology: Insulin deficiency and antagonism by counterregulatory hormones during stress - Increased glucose
production from glycogenolysis and gluconeogenesis coupled with lipolysis as the body senses a starvation mode and
enters oxidative metabolism with resultant ketone (beta-hydroxybutyrate) formation and metabolic acidosis.
Blood gases from venous or capillary origin are acceptable in nonintubated and well-perfused infants.
A 10% fluid deficit in infants with DKA can be assumed. 10 - 20 mL/kg of NS or LR over 1 - 2 hours is administered.
Once adequate intravascular volume is obtained, the remaining fluid deficit can be restored over the next 24 - 48 hrs.
Insulin is key to resolving DKA and halting lipolysis and ketone generation. Insulin infusion should begin after the
initial fluid bolus, 1 - 2 hours after the start of resuscitation. Only IV routes should be considered, because SQ and IM
absorption is irregular in the dehydrated patient.
Insulin bolus is not recommended in the pediatric population because this may exacerbate the risk of cerebral edema
by dropping blood glucose levels too quickly.
Insulin dose: 0.1 U/kg/hr with the rate adjusted to achieve a fall in blood glucose of 50 - 90 mg/dL/hr. Once the blood
glucose level falls to 300 mg/dL, glucose should be added to the IVF.
As long as acidosis is present, insulin infusion should continue with glucose to maintain levels between 150 - 200
mg/dL. Once acidosis has resolved and the patient can tolerate PO intake, SQ insulin (0.25 U/kg) can be initiated,
usually 1 - 2 hours before insulin infusion is discontinued.
DKA patients have a potassium deficit of 3 - 6 mEq/kg. Most of the deficit is intracellular.
Once insulin therapy is begun and acidosis is improved, potassium is forced back into cells, which may cause a
precipitous drop in potassium levels and lead to cardiac arrhythmias.
If potassium > 4 mEq/L, 40 mEq/L of is added to the IVF after vascular competency and urine output is restored. If the
initial potassium level is < 4 mEq/L, replacement should be started after the fluid bolus and before insulin therapy.
Phosphate depletion due to osmotic diuresis can be expected, but the benefit of phosphate replacement is unclear.
Calcium levels may decline, and phosphate infusion should be terminated if hypocalcemia occurs.
Generally, bicarbonate is not recommended, because the acidosis should self-correct during fluid resuscitation and
insulin therapy. The ADA recommends consideration if the pH remains < 7.0 after the first hour of hydration.
If given for DKA, bicarbonate is mixed as an isotonic solution (2 ampules NaHC03 in 0.45% NS), given over 1 hour.
Cerebral Edema: The most common explanation involves fluid entry into the brain due to a rapid drop in serum
osmolality concomitant with vigorous fluid resuscitation. Do not infuse > 50 mL/kg over the first 4 hours of treatment
because higher volumes have been associated with an increased risk of cerebral edema.
Patients at greatest risk for cerebral edema present with extreme acidosis, have high BUN levels, and hypocapnia.
Cerebral edema should be suspected in infants with persistent vomiting, bradycardia, hypertension, irritability, or in
the presence of neurologic findings.
Treatment has been attempted with mannitol (0.25–1.0 g/kg) or hypertonic saline (3%) given 5 - 10 mL/kg over a
period of 30 minutes. Hyperventilation in intubated patients should not be beyond the patient’s physiologic tendency.
Pseudohyponatremia can occur with hyperglycemia, hyperlipidemia, or hyperproteinemia.
In infants, hyponatremia may result from inappropriately diluted formulas.
Clinical symptoms are not usually seen until serum sodium falls < 120 mEq/L. A gradual progression of hyponatremia
may not become clinically evident even at levels < 110 mEq/L. Less severe hyponatremia may be symptomatic if the
decline in serum sodium is rapid.
Aggressive treatment with 3% hypertonic saline should only be initiated if significant symptoms are present, such as
seizures or coma. 5 mL/kg over 10 - 15 minutes should raise the sodium level by 5 mEq/L.
The exact sodium deficit can be calculated as follows: mEq Na needed = 0.6 x weight (kg) x (Na desired - Na
measured). Acute correction to a level of 125 mEq/L should alleviate symptoms in most cases.
After acute correction for symptoms, the goal is to raise the sodium level slowly at a rate of 0.5 mEq/L/hr (maximum
12 mEq/L per day) by using 0.9%NS. If SIADH is suspected, consider fluid restriction to 2/3 maintenance and
administration of furosemide.
Central pontine myelinolysis - a complication of hypertonic saline use; it has been less well described in children than
adults. Most cases are described in a setting of chronic hyponatremia. Infants can tolerate rapid and large increases
in sodium levels without sequelae.
Neonates and infants are more susceptible than older children to acidosis due to their lower renal threshold for
bicarbonate reabsorption and limited maximum net acid excretion.
Lactic acidosis is the most common cause of an increased anion gap acidosis in critically ill neonates.
Most clinicians would only use sodium bicarbonate if an inborn error is suspected or if the metabolic acidosis is
causing significant arrhythmias/hemodynamic instability. Some advocate its use in DKA with a pH < 6.9 or significant
hyperkalemia or arrhythmias, or in non-DKA metabolic acidosis with a pH < 7.1 refractory to other treatments.
The dose of sodium bicarbonate is 1 - 2 mEq/kg given IV.
Bicarbonate therapy is potentially harmful because it shifts the oxygen-hemoglobin dissociation curve to the left and
can worsen tissue hypoxia, particularly in hypovolemic patients. It can also cause hypernatremia, hypokalemia, and a
paradoxical drop in CNS pH leading to decreased consciousness.
A common ED presentation involves a newborn male with an uneventful birth history who presents within the first 2
weeks of life with apparent dehydration or sepsis and circulatory collapse unresponsive to fluid resuscitation.
Congenital adrenal hyperplasia is an important cause of primary adrenal insufficiency in the newborn period. CAH
refers to a group of inherited disorders with defects in adrenal synthesis of cortisol. Deficiency of 21-hydroxylase
accounts for up to 95% of CAH cases.
Many states now screen newborns for CAH. Males are particularly prone to missed diagnosis because their genitalia
may appear normal at birth; females usually exhibit some degree of ambiguous genitalia. Another sign is
hyperpigmentation, which may be present in the axilla and scrotal/labial areas and is due to the accumulation of a
corticotropin precursor that stimulates melanocytes.
Acute adrenal insufficiency is associated with hyponatremia, hyperkalemia, and hypoglycemia. A normal anion gap
metabolic acidosis is often seen due to aldosterone deficiency.
Unexplained hypotension unresponsive to IVF is a sign of steroid deficiency.
Hydrocortisone is the treatment of choice as it has equal glucocorticoid and mineralocorticoid effects (2-3 mg/kg).
Inborn errors of metabolism
A diverse group of hereditary disorders involving gene mutations, usually of a single enzyme or transport system,
causing significant blocks in metabolic pathways and accumulation or deficiency of a particular metabolite.
The most common emergent clinical manifestations in the neonatal period include vomiting, neurologic abnormalities,
metabolic acidosis, and hypoglycemia.
IEMs can be divided into disorders of amino acid metabolism (phenylketonuria, nonketotic hyperglycinemia), fatty acid
oxidation/metabolism (medium-chain acyl-CoA dehydrogenase deficiency, primary carnitine deficiency), energy
metabolism (primary lactic acidemias), and carbohydrate metabolism (glycogen storage diseases, galactosemia).
Organic acidemias and acidurias (methylmalonic, propionic, and isovaleric acidemias, maple syrup urine disease)
refer to a group of disorders of amino and fatty acid metabolism in which high levels of non-amino organic acids
accumulate in serum and urine.
Recurrent vomiting, dehydration, and acute metabolic encephalopathy are common clinical manifestations. Intractable
seizures are characteristic of nonketotic hyperglycinemia and pyridoxine-dependent seizures. Hepatomegaly is a
common finding and is pronounced in glycogen storage diseases and galactosemia, but is less evident in infancy.
Hypoglycemia is common and can be pronounced, particularly in glycogen storage diseases and defects of fatty acid
oxidation. Hyperammonemia is most commonly seen in organic acidemias and urea cycle defects.
Urea cycle defects:
A specific classification of IEMs which lead to hyperammonemia due to the inability to detoxify ammonia to
urea and include ornithine transcarbamylase deficiency, arginase deficiency (argininemia), and
argininosuccinic acid synthetase deficiency.
Neonates frequently present after a few days of protein feeding of either breast milk or formula.
Blood ammonia is usually > 200 mmol/L. The degree of neurologic impairment is thought to be related more
to the duration of hyperammonemia rather than the level itself. BUN is usually low.
The lack of a metabolic acidosis is helpful in differentiating urea cycle defects from many of the other IEMs.
After appropriate fluid boluses of NS, most IEMs can be managed with a standard IVF consisting of 10% dextrose in
1/4 NS at 1.5 times maintenance. Metabolic acidosis unresponsive to IVF should be treated with NaHC03 boluses of
1 - 2 mEq/kg. Correction of severe acidosis will often require large doses of bicarbonate, up to 20 mEq/kg.
Ammonia is significantly elevated in urea cycle defects and many of the organic acidemias. An ammonia level > 120
mmol/mL in a newborn is considered neurotoxic. Hemodialysis is effective to remove excessive ammonia; temporizing
empiric therapy with arginine can reduce ammonia levels acutely in most urea cycle defects.
Although both lactate and pyruvate levels can be elevated in sepsis and IEMs, the lactate-to-pyruvate ratio tends to
be increased in sepsis (> 10:1), whereas in some IEMs (e.g. primary lactic acidosis) the ratio is normal.
In the event of a failed resuscitation of a patient with a suspected IEM, permission for autopsy should be discussed.
Perimortem samples will allow for appropriate genetic counseling for current family members and future siblings.
Neonatal thyrotoxicosis (congenital hyperthyroidism) is usually due to in utero passage of thyroid-stimulating
immunoglobulins from the mother to fetus. By far, most cases are due to maternal Graves’ disease, an autoimmune
disorder that produces TSH receptor antibodies causing increased thyroid hormone release.
Infants with neonatal hyperthyroidism are commonly born preterm with low birth weight, microcephaly, and
Symptoms are transient and usually last < 12 weeks, the duration of which is dependent on the persistence of
maternally transmitted immunoglobulins. Most infants will have a goiter, and many will also have exophthalmos,
hyperthermia, tachycardia, hepatomegaly, and jaundice.
Neonatal thyrotoxicosis can be life-threatening, with a mortality rate of up to 20%, usually from heart failure.
Hyperthyroidism in older infants and children is almost always due to Graves’ disease. Unlike adults, children with
hyperthyroidism usually have an indolent progression of symptoms over months. Personality disturbances or motor
hyperactivity may be the earliest symptoms, followed by the classic symptoms of weight loss, heat intolerance,
diaphoresis, palpitations, diarrhea, and amenorrhea. A goiter is present in nearly 100% of cases.
Neonatal hyperthyroidism and thyroid storm have many therapeutic options:
Beta-adrenergic blockade is achieved with propanolol, 0.01 mg/kg IV and titrated to clinical effect
Thyroid hormone synthesis can be blocked using PTU, 5 - 10 mg/kg/d, or methimazole, 0.5 - 1 mg/kg/d, TID
Iodine (inhibits thyroid hormone secretion) can be given in the form of Lugol’s solution, 1 - 3 drops daily.
Iodine should be started at least 1 hour after administering an anti-thyroid drug like PTU to avoid increasing
thyroid gland stores before the anti-thyroid effect occurs.
Glucocorticoid treatment may also be helpful in severe cases, because it inhibits thyroid hormone release and
decreases peripheral conversion of T4 to T3.
Mahmood AR, Narang AT. Diagnosis and management of the acute red eye. Emerg Med Clin N Am.
Topical analgesics should not be prescribed, and steroids should be used only after ophthalmology consultation.
Conjunctivitis (The most common cause of red eye)
If there is no component of itching, it is less likely, and another diagnosis should be sought.
On exam, there is a global bilateral injection pattern that is equal in both eyes. A clear, watery discharge may be
present and possibly mild eyelid swelling.
Treatment: cold compresses, OTC vasoconstrictors, ocular NSAIDS, antihistamines and topical mast cell stabilizers
such as cromolyn sodium. Steroids may be used in consultation with an ophthalmologist.
Adenovirus is the most likely etiologic agent.
Common modes of transmission include fingers, medical instruments, and swimming pool water.
The patient will usually complain of irritation beginning in one eye and spreading to the other a few days later.
Common but nonspecific findings include preauricular lymphadenopathy, global conjunctival injection, watery
discharge, and a follicular reaction of the inferior tarsal conjunctiva. Follicles are tiny, avascular, round, white or gray
patches on the palpebral conjunctiva.
Pain and photophobia are not typically associated with adenoviral conjunctivitis, and blurred vision that does not clear
on blinking should prompt consideration of another diagnosis.
Topical antibiotics are not necessary: Viral conjunctivitis is usually benign and self-limiting, and there is a low
likelihood of secondary bacterial infection..
Adenovirus has been found to have a 95% replication rate at 10 days, which drops to 5% at 16 days; the patient
should be instructed to practice frequent hand washing for 2 weeks.
Two Common Syndromes of Adenovirus Subtypes
An abrupt onset of high fever, pharyngitis, and bilateral follicular conjunctivitis.
It is more common in children. Schools in the winter and camps in the summer are common settings for this infection.
Treatment is the same as for mild follicular conjunctivitis.
Associated with ocular pain and decreased visual acuity from corneal subepithelial infiltrates.
Edema, small petechial hemorrhages, and the formation of inflammatory pseudomembranes are distinctive features.
Treatment should consist of local care as for simple viral conjunctivitis.
Occurs at a higher rate in HIV-infected patients.
Usually presents unilaterally, and has many of the features of an adenovirus conjunctivitis, including a watery
discharge and palpable preauricular nodes. Pain, burning, and a FB sensation help distinguish it from most other
forms of viral conjunctivitis.
If there is no skin or corneal involvement, treatment is with cool compresses and topical antiviral medication.
If HSV conjunctivitis also involves the skin (e.g., HSV dermatitis of the eyelids) or is associated with corneal
involvement (one may see pinpoint or dendritic lesions on the cornea using fluorescein), treatment consists of topical
antiviral drops (e.g. trifluridine) and oral antivirals (e.g. acyclovir).
Steroids should not be prescribed for patients with HSV conjunctivitis because the risk for secondary infection and
other complications from uncontrolled viral proliferation is increased.
Stress, fever, trauma, or UV light can all trigger reactivation of the infection.
Occurs from reactivation of the VZV virus in the ophthalmic division of the trigeminal nerve.
Most cases involve the skin only, but serious ocular involvement can occur if the infection is reactivated in the
nasociliary branch of the ophthalmic nerve.
Herpes pustules at the tip of the nose (Hutchinson’s sign) is a predictor of ocular involvement. Patients with this sign
have twice the incidence of ocular involvement; 1/3 of patients without the sign experience ocular manifestations.
With corneal involvement, HZV dendrites appear as a branching or ‘‘medusa-like’’ pattern with tapered ends in
contrast to HSV dendrites, which often have terminal bulbs.
An ophthalmologist should be consulted regarding antiviral agents and the need for topical steroids.
Most common etiologies: Gram-positive organisms, Streptococcus pneumoniae and Staphylococcus aureus (more
often in children) and gram-negative organisms, Haemophilus influenzae (mostly afflicts adults).
Has a more abrupt onset than viral conjunctivitis; usually spreads to the contralateral eye within 48 hours.
A morning crusting from a mucopurulent yellow discharge is seen. The injection is more pronounced at the fornices.
Although it is usually a self-limiting disease, topical antibiotics shorten the course, reduce person-to-person spread,
and lowers the risk of sight-threatening complications such as ulceration.
Erythromycin and bacitracin/polymyxin B provide coverage against most pathogens found in adult and pediatric
cases. Aminoglycosides should not be used because they have relatively poor coverage of gram-positive organisms.
Topical fluoroquinolones are used for the contact lens user with an infectious corneal ulcer; ophthalmology follow-up
in 1 day is required.
Hyperacute conjunctivitis - Caused by Neisseria gonorrhoeae.
N gonorrhoeae is usually spread from genital-hand-eye contact in the young sexually active adult, but neonates can
acquire it from the birth canal. The infection will manifest in neonates 3 - 5 days postpartum with bilateral discharge.
Infection is abrupt in onset and with copious amounts of purulent discharge that reforms quickly after wiping away.
The infection may be associated with a urethral discharge. In infants born to infected mothers, the infection may be
localized to other organs (arthritis, meningitis, pneumonia) or may be disseminated (sepsis).
Topical antibiotics are the same as for bacterial conjunctivitis. Systemic antibiotics should be initiated, because a large
number of patients with N gonorrhoeae conjunctivitis also have concurrent venereal disease.
Urgent referral is critical because in contrast to bacterial conjunctivitis, hyperacute conjunctivitis can have sight-
threatening outcomes secondary to ulceration and perforation.
Ocular Chlamydial Infection
Trachoma - a chronic keratoconjunctivitis that is the most common form of preventable blindness in the world.
Inclusion conjunctivitis - a common, primarily sexually transmitted disease that affects both newborns and adults:
Inclusion conjunctivitis is more common than N gonorrhoeae infection in newborns. Newborns acquire the
infection in the birth canal and present with tearing, conjunctival inflammation, and eyelid swelling with
moderate discharge 5 - 12 days after birth. Systemic antibiotics in addition to topical agents are used because
of the association with otitis media and respiratory and GI infections.
In adults, inclusion conjunctivitis is transmitted via genital secretions and may result from autoinoculation.
There will be redness, FB sensation, mucopurulent discharge, and preauricular adenopathy. Up to half of
adults will have concurrent, possibly asymptomatic cervical/urethral chlamydial infection.
The patient may recall a history of mild trauma or valsalva (such as coughing or vomiting). When it is spontaneous, it
is usually secondary to decreased lubrication of the eye.
Consider staining the eye to rule out corneal injury if the patient has any type of associated pain.
In the setting of trauma with a large hemorrhage, consider globe rupture.
Warm compresses and lubrication drops may help reduce recovery by 1 - 3 days. A high-profile subconjunctival
hemorrhage will take approximately 10 to 14 days to resolve.
Episclera - a thin membrane that covers the sclera and lies beneath the conjunctiva.
Episcleritis is a benign inflammatory condition that involves only the superficial episcleral tissue.
Most cases are idiopathic, but it can be associated with systemic diseases such as RA, SLE, sarcoidosis, and
Usually characterized by a rapid onset of redness that may be associated with a feeling of grittiness and a dull
headache. Vision is unaffected, and discharge, if present, is usually watery.
On exam, there are focal areas of redness rather than a diffuse process. White sclera may be seen between radially
coursing dilated episcleral vessels.
This condition is usually self-limiting and will resolve within 2 - 3 weeks. Treatment involves NSAIDs +/- steroids.
Scleritis is classified as anterior or posterior; anterior scleritis is further subdivided into diffuse, nodular, or necrotizing.
Most cases of scleritis are immune mediated, but it can also be triggered by infection, surgery, malignancy, or drugs.
Up to half of cases are associated with a systemic disorder.
A large number of connective tissue disorders are associated with scleral disease; the most common is RA.
Wegener’s granulomatosis is the most common vasculitis associated with scleritis. Herpes zoster ophthalmicus is the
most common infectious cause of scleritis.
Scleritis usually occurs in white, middle-aged women. The characteristic feature of scleritis is severe pain that may
involve the orbit and radiate to the ear, scalp, face, and jaw. It is usually dull, boring, and can be so severe that it often
awakes the patient from sleep. It can be associated with photophobia, tearing, and with pain on accommodation.
The vascular engorgement of the deep episcleral plexus gives the eye a characteristic bluish-violet discoloration, and
the deep scleral vessels will not blanch in response to vasoconstrictor agents. This is in contrast to the blanching seen
with conjunctival and superficial vessels in conjunctivitis and episcleritis.
In scleritis, the vascular architecture of the superficial episcleral plexus is disrupted by the presence of irregularly
oriented vessels. In episcleritis, only the superficial episcleral plexus is congested, and its radial configuration is
preserved. Avascular areas strongly imply the diagnosis of necrotizing scleritis.
In isolated posterior scleritis, the eye may be white, but sometimes inflamed posterior sclera can be visualized in the
extremes of gaze. Because there may be a paucity of findings on exam, imaging is often necessary to make the
diagnosis. Posterior scleritis can be diagnosed using ultrasonography and orbital MRI .
Early diagnosis is important because of the development of serious complications (e.g. visual impairment, glaucoma,
cataracts). Greater visual loss is generally seen in patients with systemic disease, especially in RA.
The goal of treatment is to treat the underlying cause and to control the inflammatory process. Treatment includes
NSAIDS, systemic steroids, and more aggressive systemic immunosuppression.
Uveitis is an inflammation of the iris (iritis), ciliary body (cyclitis), and choroid (choroiditis). Anterior uveitis, often called
iridocyclitis, involves inflammation of the anterior portion of the uveal tract. Posterior uveitis includes vitritis, choroiditis,
Uveitis can be characterized as inflammatory, traumatic, or infectious. Uveitis has been shown to be associated with
antigen HLA B-27. Thus, there is an association with systemic disease such as ankylosing spondylitis, psoriatic
arthritis, and inflammatory bowel disease. Many other systemic diseases may present with uveitis, including
sarcoidosis, Kawasaki disease, multiple sclerosis, and Wegener’s granulomatosis.
Toxoplasmosis is a common cause of retinochoroiditis in both normal and immunosuppressed patients and is
responsible for as many as 25% of occurrences of posterior uveitis in the US.
CMV can cause posterior uveitis in immunocompromised individuals, particularly in AIDS patients.
Traumatic iritis is commonly seen in the ED and is usually secondary to a direct blow from a blunt object.
Anterior uveitis - presents suddenly with a red and painful eye. Photophobia and conjunctival injection are often seen.
Patients generally complain of a deep aching pain that may radiate to the periorbital or temple area that is worse with
eye movement and during accommodation.
Perilimbal hyperemia is prominent, in contrast to that seen in conjunctivitis in which inflammation tends be
more prominent at a distance from the limbus. Generally, the pupil is constricted.
Posterior uveitis - can cause "floaters" and visual changes but generally does not cause redness or significant pain.
The diagnosis of uveitis is often confirmed by the presence of inflammatory cells and a proteinaceous flare in the
anterior or posterior chambers of the eye on slit lamp examination. If inflammation is severe, leukocytes can settle in
the anterior chamber and form a hypopyon, a white or yellowish accumulation of purulent material.
Deposits of WBCs on the endothelium (keratitic precipitates) are often visualized, which is a hallmark of iritis.
Associated symptoms may prompt an evaluation for systemic disease. For example, patients with pulmonary
complaints should undergo chest imaging to assess for possible sacoidosis. Colonoscopy should be done in patients
with GI symptoms to assess for inflammatory bowel disease.
Corticosteroids are the mainstay of therapy in treating noninfectious causes.
Mydriatics are used to prevent the formation of synechiae by pupillary dilation. A synechia is an adhesion where the
iris adheres to either the cornea or lens; they can lead to secondary glaucoma.
Acute angle-closure glaucoma
AACG develops when the peripheral tissue of the iris blocks the outflow of fluid from the anterior chamber, resulting in
elevated intraocular pressure.
Mydriasis, such as in the low-light evening hours, can often worsen the condition as the accordion-like folds of the iris
gather together to cause obstruction. Mydriatic medications, systemic anticholinergics, and accommodation (i.e.,
reading) can also cause pupillary block.
The patient usually presents with severe ocular pain, redness, a decrease in vision, and a pupil in mid-dilation. Blurred
vision, seeing halos around lights, and headache with N/V may also be present.
Patients who are elderly or far-sighted are at the highest risk for AACG because of enlargement of their lenses.
On exam, there will usually be diffuse injection. Corneal edema may make the cornea appear "steamy" or "hazy". The
pupil will be mid-dilated and nonreactive. If the pupil reacts, the diagnosis should be reconsidered.
There may be keratitic precipitates, anterior chamber cells and flare, posterior synechiae, and a shallow anterior
chamber. A fundoscopic examination that reveals optic nerve cupping indicates the need for urgent treatment.
Normal IOP is < 21 mm Hg. AACG patients with an IOP > 30 mm Hg require prompt treatment.
Treatment in the ED includes topical timolol and topical steroids. One dose of a topical α2-adrenergic agonist
(apraclonidine or brimonidine) should be given. Acetazolamide is given, 500 mg PO, to help decrease the production
of fluid. In cases of phakic pupillary block (in which there is a native, natural lens), pilocarpine, can be administered.
If vision has been significantly, IV acetazolamide, and IV mannitol may be indicated.
Definitive treatment includes peripheral iridotomy performed by laser or incision. The fellow eye should receive a
prophylactic iridotomy based on anatomy, because about half of fellow eyes will sustain acute attacks within 5 years.
Schlosser RJ. Epistaxis. N Engl J Med. Feb 2009;360(8):784-789.
> 90% of epistaxis occurs at the anterior nasal septum, at Kiesselbach's area, which receives blood from the terminal
branches of the sphenopalatine, ethmoidal, and superior labial arteries.
10% of nosebleeds occur posteriorly, which occur along the nasal septum or lateral nasal wall and are supplied by the
sphenopalatine artery. Posterior nosebleeds are more common in older patients (mean age 64 years).
Causes - Trauma is common - nose picking and mucosal trauma from topical drugs, e.g., corticosteroids or
antihistamines. Incidence of epistaxis is reduced if patients direct the spray laterally to minimize the effect of these
medications on the septum.
Dehumidification of the nasal mucosa underlies many nosebleeds during the winter months.
Low-dose aspirin increases the risk of epistaxis slightly; alternative therapies (e.g. garlic, ginkgo, ginseng) may
contribute to mild systemic coagulopathies that result in epistaxis.
HTN - One study showed no association between HTN and epistaxis and another found that the incidence of epistaxis
was not related to the severity of HTN. However, other studies have reported elevated BP in patients with epistaxis.
Hereditary hemorrhagic telangiectasia is a genetic disorder that often results in nosebleeds.
Sprays of anesthetics and vasoconstrictors, such as combinations of lidocaine or ponticaine with phenylephrine or
oxymetazoline, allow for bleeding control to permit adequate examination.
In patients with significant posterior bleeding, a transpalatal injection of the sphenopalatine artery is performed by
injecting 1% lidocaine with epinephrine through the descending palatine foramen just medial to the upper 2nd molar.
Even when performed selectively, coagulation studies are normal in 80% of patients.
Repeated episodes, particularly if they are unilateral or accompanied by other nasal symptoms, should warrant
radiographic and endoscopic evaluation to rule out neoplastic processes.
Most anterior nosebleeds are self-limited - can be controlled by tamponading the anterior septal vessels by pinching
the nasal ala against the septum for 15 minutes.
In one study, oxymetazoline spray stopped the bleeding in 65% of ED patients with epistaxis.
Chemical cautery with silver nitrate:
Found to control epistaxis in just over half of patients whose bleeding did not respond to topical
vasoconstrictors and pressure.
Only one side of the septum is cauterized at a time to reduce risk of septal perforation. When bilateral septal
cautery is needed, the treatments should be separated by 4 - 6 weeks to allow for mucosal healing.
Anterior Nasal Packings:
• are left in place for 1 - 3 days
• stops bleeding in 60 - 80% of cases refractory to vasoconstrictors and pressure
• in addition to commercial devices, a variety of degradable materials that do not require removal are
available. In one trial, bovine gelatin–human thrombin (FloSeal) was more effective than Rapid Rhnio
or Merocel, with less discomfort.
Posterior packing with inflatable balloons may be needed for bleeding from the sphenopalatine artery. Posterior packs
stop epistaxis in 70% of patients with posterior bleeding.
When nasal packs are in place, topical antibiotic ointments that coat the nasal packing or oral antibiotics are often
used to prevent toxic shock syndrome. There are no data showing that antibiotics reduce the risk.
Patients with bilateral anterior or posterior nasal packs are typically admitted to the hospital for monitoring of oxygen
saturation because of the potential for apneic spells.
If above measures fail to stop the bleeding, embolization or surgical ligation of the offending vessels is needed.
Interventional radiologists can embolize the distal branches of the internal maxillary artery and sphenopalatine artery
for posterior nosebleeds. Success rates are 80 - 90%.
Endoscopic surgical ligation of the sphenopalatine artery has success rates > embolization and avoids the risks
associated with angiography, but requires general anesthesia.
Overall costs are decreased by > 50% when posterior nosebleeds are treated with posterior packs for immediate
control and followed by endoscopic ligation of the sphenopalatine artery, and allows for earlier hospital discharge.
When surgical intervention is necessary for anterior epistaxis (rare), embolization of the ethmoid arteries is usually not
performed because of the risk of cannulating the internal carotid artery. Most ENTs perform external ligation of the
anterior and posterior ethmoidal arteries through a small incision near the medial eyebrow and cauterize/clip the
vessels within the orbit just before exiting through the anterior and posterior ethmoidal foramina.
Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. July 2009;361(1):62-72.
Rhabdomyolysis = the dissolution of skeletal muscle
Characterized by the leakage of muscle-cell contents into the circulation: electrolytes, myoglobin, and other
sarcoplasmic proteins (e.g., creatine kinase, aldolase, LDH, ALT and AST).
Recurrent episodes of rhabdomyolysis are often a sign of an underlying defect in muscle metabolism.
Pathogenic mechanisms of rhabdomyolysis:
• Direct sarcolemmic injury (e.g., trauma).
• Depletion of ATP within the myocyte -----> impairs the function of cellular pumps that maintain low levels of
calcium when muscles are at rest -----> unregulated increase in intracellular calcium -----> results in activation
of enzymes ultimately leading to lysosomal digestion of muscle fiber contents.
Major Categories of Causes of Rhabdomyolysis
Exertion e.g. exercise, seizure, ETOH withdrawal
Muscle Hypoxia Limb compression; Major artery occluision
Infections e.g. influenza, HIV, EB virus, streptococcus,
Metabolic Disorders DKA, hypokalemia, hypophosphatemia
Drugs & Toxins Statins, heroin, cocaine, ETOH
Epidemiology of Myoglobinuria-Induced Acute Kidney Injury
Acute kidney injury associated with myoglobinuria - the most serious complication of rhabdomyolysis - is quite
common, representing 7 - 10% of all cases of acute kidney injury in the US.
Reported incidence of acute kidney injury in rhabdomyolysis: 13% - 50%. The incidence is higher among persons who
use illicit drugs or abuse alcohol and among those who have undergone trauma than those with muscle disease.
The majority of patients with rhabdomyolysis-induced acute kidney injury recover renal function.
Pathogenesis of Myoglobin-Induced Acute Kidney Injury
Myoglobinuria occurs only in the context of rhabdomyolysis. Not all cases of rhabdomyolysis are associated with
myoglobinuria - the serum myoglobin concentration needs to exceed the renal threshold for it to appear in the urine.
Mechanisms of kidney injury:
• Intrarenal vasoconstriction - a characteristic feature of rhabdomyolysis-induced acute kidney injury that results
from several mechanisms that induce the release of vascular mediators.
• Direct tubule injury mediated by myoglobin-associated oxidative injury and tubular damage due to ischemia.
• Tubular obstruction: Myoglobin precipitates when it interacts with the Tamm-Horsfall protein (a glycoprotein
excreted by the loop of Henle), a process favored by acidic urine. Tubular obstruction occurs due to
precipitation of the TH protein-myoglobin complex.
Renal Manifestations of Rhabdomyolysis
Patients with acute rhabdomyolysis usually present with pigmented granular casts, reddish-brown urine supernatant,
and markedly raised serum creatine kinase.
There is no defined level of serum creatine kinase above which the risk of acute kidney injury is markedly increased.
There is a very weak correlation between the peak creatine kinase value and the incidence of acute kidney injury.
The risk of acute kidney injury is usually low when admission creatine kinase levels are < 15,000 - 20,000 U/L.
Although acute kidney injury may be associated with creatine kinase values as low as 5000 U/L, this usually occurs
when coexisting conditions such as sepsis, dehydration, and acidosis are present.
Myoglobinuria can be inferred if urinary dipstick testing shows when there are no red cells in the sediment.
A positive result for blood on urinary dipstick has a sensitivity of 80% for the detection of rhabdomyolysis. This false
positive result for blood occurs because the dipstick test is unable to distinguish between myoglobin and hemoglobin.
Even though myoglobin is the true pathogenic factor in rhabdomyolysis-induced acute kidney injury, measurement of
serum myoglobin has a low sensitivity for the diagnosis of rhabdomyolysis: Serum myoglobin levels peak well before
serum creatine kinase levels, and serum myoglobin has a rapid and unpredictable metabolism.
A low BUN:creatinine ratio is often seen in patients with rhabdomyolysis.
The fractional excretion of sodium is a measurement of the percentage of filtered sodium that is excreted in the urine,
and low levels in patients with acute kidney injury are an indication of the relative integrity of tubular functions.
However, when ATN is established, both urinary sodium and the fractional excretion of sodium are raised.
A characteristic feature of rhabdomyolysis-induced acute kidney injury that is different from other forms of ATN is the
presence of a low fractional excretion of sodium (<1%), reflecting the primacy of preglomerular vasoconstriction and
tubular occlusion rather than tubular necrosis.
Electrolyte Abnormalities - may precede the acute kidney injury:
• hyperkalemia - an early manifestation of rhabdomyloysis - The authors' recommend checking potassium levels
Q4hrs in cases of severe rhabdomylosysis. Consider an EKG upon arrival.
• hyperuricemia - can contribute to renal tubule obstruction since uric acid is insoluble and may precipitate in
• hyperp hosphatemia
• hyperm agnesemia
• hypocalcemia - aggravates the adverse electrical effects of hyperkalemia
• high anion-gap metabloic acidosis
Hypercalcemia associated with recovery of renal function is unique to rhabdomyolysis-induced acute kidney injury and
results from the mobilization of calcium that was previously deposited in muscle, the normalization of
hyperphosphatemia, and an increase in calcitriol.
Treatment and Prevention
Fluid resuscitation - patients often require > 10 liters of fluid per day.
Alkalinization - The literature is contradcitory regarding the clinical benefits of alkalinization; Animal studies suggest 3
potential benefits: (1) precipitation of the Tamm–Horsfall protein–myoglobin complex is increased in acidic urine (2)
alkalinization inhibits reduction-oxidation cycling of myoglobin, thus ameliorating tubule injury (3) metmyoglobin
induces vasoconstriction only in an acidic medium.
Probably the only disadvantage of alkalinization is the reduction in ionized calcium, which can exacerbate the
symptoms of the initial hypocalcemic phase of rhabdomyolysis.
Massive infusion of NS can contribute to metabolic acidosis, due to the dilution of serum bicarbonate with a solution
high in chloride ions, generating hyperchloremic metabolic acidosis. Thus, administration of both NS and NaHC03 is
reasonable when fluid is being replenished in patients with rhabdomyolysis, especially those with metabolic acidosis.
If NaHC03 is used, urine pH and serum bicarbonate, calcium, and potassium levels should be monitored, and if the
urine pH does not rise after 4 - 6 hours of treatment or if symptomatic hypocalcemia develops, alkalinization should be
discontinued and hydration continued with normal saline.
Diuretics - use is controversial, but it is clear that it should be restricted to patients in whom the fluid repletion has
Mannitol - offers several potential benefits as it increases urinary flow and the flushing of nephrotoxic agents through
the renal tubules, is an osmotic agent so improves hypovolemia, and is a free-radial scavenger.
Although no randomized, controlled trial has supported its use, many experts continue to use mannitol to prevent and
treat rhabdomyolysis-induced acute kidney injury. During mannitol administration, plasma osmolality and the osmolal
gap (i.e., the difference between the measured and calculated serum osmolality) should be monitored frequently and
therapy discontinued if adequate diuresis is not achieved or if the osmolal gap rises > 55 mOsm/kg.
Loop diuretics also increase urinary flow and may decrease the risk of myoglobin precipitation, but no study has
shown a clear benefit in patients with rhabdomyolysis.
Agents that cause a shift of potassium from the extracellular to the intracellular space (e.g., hypertonic glucose and
bicarbonate) are effective only temporarily - typically serum potassium will be lowered in 10 - 30 minutes and the
effect will last for 2 -6 hours.
Early hypocalcemia should not be treated unless it is symptomatic or unless severe hyperkalemia is present.
Conventional hemodialysis does not remove myoglobin effectively owing to the size of the protein and is therefore
usually mandated by renal indications.
Management - Authors' Recommendations
NS @ 400 ml/hr (200 - 1000 ml/hr depending upon severity)
Target urine output of 3 ml/kg/hr
If urine pH < 6.5, alternate each liter of NS with 1 liter D5W or 0.45% NS plus 100 mmol of HC03.
Avoid potassium and lactate-containg solutions
Consider treatment with mannitol (up to 200 g/d and cumulative dose up to 800 g. Follow plasma
osmolal gap. Discontinue if diuresis (< 20 ml/hr) is not established
Maintain volume repletion until myoglobinuria is cleared
Singh A, Alter HJ, Littlepage A. A systematic review of medical therapy to facilitate passage of ureteral
calculi. Ann Emerg Med. Nov 2007;50(5):552-563.
The majority of individuals with urolithiasis have small (<5 mm) stones located in the distal ureter, that pass
spontaneously. Both stone expulsion and time to expulsion of ureteral stones depend upon stone size and location.
Urologic intervention is recommended for ureteral stones that persist for > 2 months.
Ureteral smooth muscle contraction is driven by an increase in intracellular calcium and is modulated by the
autonomic nervous system. Both α-antagonists and calcium channel blockers have been shown to inhibit the
contraction of ureteral muscle responsible for ureteral spasms while allowing antegrade stone propagation.
Study Objective: Literature review on the use of medical expulsive therapy to facilitate ureteral stone expulsion.
Analysis of 16 studies using an α-antagonist and 9 studies using a calcium channel blocker indicated that these
agents significantly improved spontaneous stone expulsion (α-antagonist RR = 1.59; NNT = 3.3) ; calcium channel
blocker RR = 1.50; NNT = 3.9) in patients with distal ureteral stones. [RR = risk ratio]
Tamsulosin (daily 0.4 mg for 1 month) was used in the majority of α-antagonist trials; in a few, terazosin or doxazosin
was used with similar efficacy. The success of these trials suggests that the benefit of α-antagonists may be a class
effect and not specific to tamsulosin. Nifedipine was the only calcium channel blocker used in the reviewed trials.
The use of an α-antagonist was associated with a 2 - 6 day reduction in time to stone expulsion. The mean time to
stone expulsion, was < 14 days in these trials and < 28 days in the calcium channel-blocker trials; thus a 2 - 4 week
time course of these medications is warranted.
In the α-antagonist trials, the overall range of stone size was 3 - 18 mm, with a mean stone diameter > 5 mm in all
trials except 2. In the calcium-channel blocker trials, the average stone size was > 5 mm in all trials except 3.
Overall, 4% of patients receiving α-antagonists and 15% of patients receiving calcium channel-blockers experienced
adverse effects. Most adverse effects were mild. Only 1 patient (0.2%) required discontinuation of α-antagonist
therapy during treatment, and 10 patients (2.9%) required discontinuation of calcium channel blocker therapy.
Small (< 5-mm) distal ureteral stones will most likely spontaneously pass within 4 weeks, without the need for urologic
intervention. Separate analysis of 2 studies with tamsulosin and analysis of 3 studies with nifedipine for stones up to 5
mm suggest some improvement in the stone expulsion rate and time to expulsion with the addition of either agent.
The addition of a low-dose steroid is thought by some to prevent edema around the ureteral stone and slowing of
stone passage. The results of 2 trials comparing stone passage rates in patients receiving tamsulosin plus low-dose
steroid to tamsulosin alone were mixed.
No trials were found comparing α-antagonists to calcium channel blockers.
Conclusion - “Medical expulsive therapy,” using either α-antagonists or calcium channel blockers, augments the stone
expulsion rate compared to standard therapy for moderately sized distal ureteral stones.
Vilke GM, Ufberg JW, et al. Evaluation and treatment of acute urinary retention. J Emerg Med.
The incidence of AUR is almost 1/3 of men in their 80s.
The most common cause of AUR is benign prostatic hypertrophy. Other obstructive causes and medications that can
induce retention account for most of the rest of cases.
Treatment: Foley catheter ----> Coudé catheter ----> Suprapubic catheterization
Foley Catheter Placement
Contraindications: abdominopelvic trauma with blood at the meatus, an obvious penile deformity, a high-riding
prostate, or a perineal hematoma.
Pearls to Aid Placement: Inject lidocaine jelly directly into the urethral meatus; do not inflate the balloon until the
bladder has been accessed. The biggest error in Foley catheter placement in women is mistaking the clitoris for the
urethra. The urethra is more posterior and has a slit-like opening.
Coudé Catheter Placement
The Coudé catheter is inserted into the meatus with the curved tip pointing up, cephalad, and is advanced with gentle
but continuous pressure past the resistance point, typically in the region of an enlarged prostate.
Typically used after Foley failure in a man with an enlarged prostate.
Care should be taken in patients with a history of urethral strictures who have failed Foley catheter placement, as
false tracts may have been created that can be extended by a Coudé.
Suprapubic Catheterization - Used when urethral cath is contraindicated (e.g. pelvic trauma with blood at meatus)
Contraindications: Empty bladder, previous lower abdominal surgery with scarring, and previous pelvic radiation with
scarring. Bleeding disorders are a relative contraindication.
First, the bladder is identified with palpation, or use of ultrasound. The insertion site is 2 cm cephalad to the pubic
bone. A suprapubic catheter is inserted via a guidewire technique followed by a dilator and sheath.
Gross hematuria is a frequent, but usually transient occurrence. Bladder irrigation may be needed.
Paraphimosis Manual Reduction
Before performing, remove the Foley catheter if one is in place to facilitate reduction.
Prior to attempted reduction, slow gentle pressure should be applied by grasping the swollen foreskin to reduce
edema. Alternatively, a 5- or 6-cm elastic bandage may be placed for a few minutes.
Phimosis without ability to void or ischemia to penis is the emergent indication for performing a dorsal slit. Bleeding
dyscrasia is the only relative contraindication.
The foreskin is cut along the dorsal aspect of the penis after local anesthesia and use of a hemostat to create an area
of clamped, serrated skin amenable to incision.
Cooper LT. Myocarditis. N Engl J Med. April 2009;360(15):1526-1538.
Clinical Manifestations and Incidence
Pathological Definition: an inflammatory cellular infiltrate with or without associated myocyte necrosis present on
conventionally stained heart-tissue sections.
Acute myocarditis is frequently first diagnosed as nonischemic dilated cardiomyopathy in a patient with symptoms that
have been present for a few weeks to several months.
Although a viral prodrome with fever, myalgia, and respiratory or GI symptoms is classically associated with
myocarditis, symptoms are variable and clinical manifestations can range from subclinical disease to sudden death.
In one large study of patients with suspected acute or chronic myocarditis, 72% had dyspnea, 32% had chest pain,
and 18% had arrhythmias.
Children often have a more fulminant presentation.
Most people with myocarditis who present with acute dilated cardiomyopathy have relatively mild disease that
resolves with few short-term sequelae, but certain clinical clues signify those at high risk:
• Rash, fever, peripheral eosinophilia, or a temporal relation with recently initiated medications suggest a
possible hypersensitivity myocarditis.
• Giant-cell myocarditis should be considered with acute dilated cardiomyopathy associated with thymoma,
autoimmune disorders, ventricular tachycardia, or high-grade heart block.
• An unusual cause of myocarditis (e.g. cardiac sarcoidosis) should be suspected in patients who present with
chronic heart failure, dilated cardiomyopathy and new ventricular arrhythmias, or high grade AV block, or who
do not have a response to standard care.
A long-term study of pediatric myocarditis showed that the greatest burden of myocarditis may not be apparent for 6 -
12 years after diagnosis when children die or undergo cardiac transplantation for chronic dilated cardiomyopathy.
Viral and postviral myocarditis remain major causes of acute and chronic dilated cardiomyopathy.
Coxsackievirus B is linked to outbreaks of myocarditis from the 1950s through the 1990s.
Viruses detected on endomyocardial biopsy has shifted from coxsackievirus B to adenovirus in the late 1990s and, in
the past 5 years, to parvovirus B19 and other viruses. Hepatitis C virus has also been linked to myocarditis.
Other infectious causes of myocarditis:
• Lyme disease - should be suspected in patients with a history of travel to endemic regions or of a tick bite,
particularly if they also have AV conduction abnormalities.
• In areas of Central and South America, Trypanosoma cruzi infection can present as acute myocarditis or
chronic cardiomyopathy, sometimes with RBBB or left anterior fascicular block.
Myocarditis is the most common cardiac autopsy finding of HIV patients, with a prevalence of 50% or more.
Drug-induced hypersensitivity reactions - responds to withdrawal of the offending agent, though corticosteroid therapy
is often required. Anticonvulsants, antibiotics, and antipsychotics, have been implicated.
Eosinophilic myocarditis - may occur in association with systemic diseases, such as the hypereosinophilic syndrome,
the Churg–Strauss syndrome, Löffler's endomyocardial fibrosis, cancer, and parasitic, helminthic, or protozoal
infections; has been reported after vaccination for several diseases, including smallpox.
Manifestations of eosinophilic myocarditis include CHF, endocardial and valvular fibrosis, and endocardial thrombi.
Giant-cell myocarditis - an acute disorder with a high risk of death or need for cardiac transplantation, is primarily
autoimmune in nature. Giant-cell myocarditis is sometimes distinguished from the more common postviral myocarditis
by the presence of ventricular tachycardia, heart block, and a downhill clinical course, despite optimal care.
Viruses appear to enter cardiac myocytes or macrophages through specific receptors.
According to animal models, progression from acute injury to chronic dilated cardiomyopathy may be simplified into a
(1) Acute injury leads to cardiac damage, exposure of intracellular antigens, and activation of the immune system.
(2) Over weeks, immunity mediated by T lymphocytes and antibodies directed against pathogens and similar
endogenous heart antigens cause robust inflammation.
(3) In most patients, the pathogen is cleared and the immune reaction is down-regulated with few sequelae.
However, in other patients, the virus is not cleared and causes persistent myocyte damage, and heart-specific
inflammation may persist because of mistaken recognition of endogenous heart antigens as pathogenic entities.
Cardiac biomarkers are elevated in a minority of patients with acute myocarditis. Troponin I has high specificity (89%)
but limited sensitivity (34%) in the diagnosis of myocarditis.
In acute myocarditis, the EKG may show sinus tachycardia with nonspecific ST-T-wave abnormalities. Pericarditis
often accompanies myocarditis clinically and is often manifested in pericarditis-like EKG changes. The sensitivity of
the EKG for myocarditis is low (47%).
The presence of Q waves or LBBB is associated with higher rates of death or cardiac transplantation.
Echocardiography is useful primarily to rule out other causes of heart failure, since there are no specific features of
Fulminant myocarditis may be distinguished from acute myocarditis by a smaller LV cavity size and increased wall
thickness. The loss of RV function was the most powerful predictor of death or the need for cardiac transplantation in
a series of 23 patients with biopsy-confirmed myocarditis.
Cardiac MRI is being used with increasing frequency as a diagnostic test in suspected acute myocarditis and may be
used to localize sites for endomyocardial biopsy.
Indications for endomyocardial biopsy
• unexplained, new-onset heart failure of < 2 weeks duration in association with a normal-size or dilated left
ventricle and hemodynamic compromise, for suspected fulminant myocarditis
• unexplained, new-onset heart failure of 2 weeks - 3 months duration in association with a dilated LV and new
ventricular arrhythmias or high grade AV block
• lack of response to usual care within 1 - 2 weeks, for suspected giant-cell myocarditis
The mainstay of therapy for acute myocarditis is standard supportive therapy for LV dysfunction and application of
current heart-failure guidelines; most patients will improve.
In patients whose condition deteriorates despite optimal medical management, there is a role for mechanical
circulatory support, such as ventricular assist devices or ECMO, as a bridge to transplantation or recovery. The
overall rate of survival after cardiac transplantation for myocarditis is similar to that for other causes of cardiac failure.
Based upon animal studies, patients recovering from acute myocarditis should refrain from aerobic activity for a period
of months after the clinical onset of the disease.
The use of NSAIDs is associated with increased mortality.
In patients with acute myocarditis, therapy for arrhythmias is also supportive, since such arrhythmias usually resolve
after the acute phase of the disease, which can last several weeks.
In some studies, the finding of viral genomes on endomyocardial biopsy was associated with subsequent worsening
of heart function, the need for cardiac transplantation, and death.
Data regarding the use of antivirals are limited. Because most patients with acute viral myocarditis are diagnosed
weeks after viral infection, it is unlikely that antiviral therapy would be provided early enough to be of benefit.
The routine use of IV immune globulin for acute myocarditis in adults is not recommended.
McCord J, Jneid H, et al. Management of cocaine-associated chest pain and myocardial infarction.
Circulation. April 2008;117:1897-1907.
Cocaine is the 2nd most commonly used illicit drug in the US, and is the illicit drug that leads to the most ED visits.
14% of people aged > 12 years in the US have tried cocaine at least once, and over 2000 individuals per day use
cocaine for the first time.
In 2005, there were > 400,000 cocaine-related ED visits in the US. They increased by 47% from 1999 to 2002.
Cocaine causes myocardial ischemia or MI in a multifactorial fashion:
(1) Increases myocardial oxygen demand:
• Cocaine blocks the reuptake of NE and dopamine, causing an accumulation of catecholamines at the
postsynaptic receptor and thus acting as a powerful sympathomimetic agent.
• Cocaine causes increased HR and BP in a dose-dependent fashion. The chronotropic effects of cocaine use
are intensified in the setting of alcohol use.
• Cocaine can reduce LV function and increase end-systolic wall stress.
(2) Decreases oxygen supply via vasoconstriction:
• Even small doses of intranasal cocaine are associated with coronary artery vasoconstriction, which is more
accentuated in patients with preexisting CAD.
• The combination of cocaine and cigarette use results in greater increases in HR and vasoconstriction than
either cocaine use or cigarette smoking alone.
• Vasoconstriction in the setting of cocaine use is most likely secondary to stimulation of
α-adrenergic receptors in smooth muscle cells in the coronary arteries.
• Cocaine increases levels of endothelin-1, which is a powerful vasoconstrictor, and decreases production of
nitric oxide, which is a vasodilator.
(3) Induces a prothrombotic state:
• The propensity for acute thrombus formation in the setting of cocaine use may be mediated by an increase in
• Cocaine use has also been associated with an increase in platelet count, increased platelet activation, and
(4) Accelerates atherosclerosis:
• Autopsy studies in young users demonstrate that cocaine use is associated with premature coronary
atherosclerosis and thrombosis.
Incidence of Myocardial Infarction
The incidence of cocaine-associated MI varies in studies from 0.7% to 6% of those presenting with chest pain after
cocaine ingestion (some of the variance is from differences in MI diagnostic criteria and in the populations studied).
In a study of 130 patients with cocaine-associated MI, the average age was only 38 years.
In one study, only 44% of patients with cocaine-associated MI reported antecedent chest pain. The presence of chest
pain has little value for discriminating an ischemic from nonischemic cause in cocaine users presenting to the ED.
Aortic dissection must be considered in the differential diagnosis of cocaine-associated chest pain.
An acute pulmonary syndrome, "crack lung", involves hypoxemia, hemoptysis, respiratory failure, and diffuse
pulmonary infiltrates and occurs after inhalation of freebase cocaine.
Timing Between Cocaine Use and Myocardial Infarction
Cocaine-associated MI appears to occur most often soon after cocaine ingestion. In one study, 2/3 of MIs occurred
within 3 hours of cocaine ingestion.
The onset of ischemic symptoms can still occur several hours after cocaine ingestion. Studies report a range
extending from 1 minute to up to 4 days from cocaine use to MI onset.
Such findings are attributed to cocaine metabolites, which rise in concentrations several hours after cocaine ingestion,
persist in the circulation for up to 24 hours, and may cause delayed or recurrent coronary vasoconstriction.
Patient Characteristics - the majority of cocaine-associated MI patients are young, nonwhite, and smokers. These
characteristics are similar in most patients presenting with cocaine-associated chest pain, making it very difficult to
predict those at risk for MI, given the low incidence of cocaine-associated MI.
Complications and Prognosis
Cocaine-Associated MI Study of 130 patients - 90% of complications (e.g. arrhythmias) occurred within the first 12
hours after presentation and did not lead to significant adverse events, with an in-hospital mortality rate of 0%.
Urine assays detect the cocaine metabolite benzoylecgonine which can be detected for about 24 - 48 hours after
cocaine use. Among individuals with long-term cocaine use, benzoylecgonine has been detected at 22 days.
An abnormal ECG has been reported in 56% - 84% of patients with cocaine-associated chest pain; however, many of
these patients have early repolarization, which may be interpreted as an abnormal ECG. In one study, early
repolarization was noted in 32% of patients with cocaine-associated chest pain ; a normal EKG was found in only 33%
In one study, the sensitivity of an ECG for ischemia or MI to predict a true MI was only 36%.
Cardiac Biomarkers - Cocaine ingestion may cause rhabdomyolysis with consequent elevation in myoglobin and total
creatine kinase levels. Cardiac troponins are preferred in patients with possible ACS in the setting of cocaine use.
Myocardial Perfusion Imaging - Rest myocardial perfusion imaging has been evaluated in the ED in low- to moderate-
risk patients after cocaine use. 1 study is cited: Of 216 patients, only 5 had positive results.
Long-term cocaine use appears to be associated with concentric LV hypertrophy. This may explain the baseline ECG
changes associated with cocaine use. This may also decrease the utility of echocardiography to look for ischemia in
the evaluation of chest pain, as LVH often masks regional wall motion abnormalities.
Dobutamine stress echocardiography has been safely performed in subjects admitted with chest pain after cocaine
use, provided they exhibited no signs of ongoing cocaine toxicity.
The appropriate diagnostic evaluation for these patients remains unclear. Given the underlying EKG abnormalities, if
a stress test is ordered, patients would benefit from stress testing with imaging, either echocardiography or nuclear.
Coronary Angiography - In studies of cocaine-related MI patients, about 80% patients had significant CAD.
Evaluation in a Chest Pain Unit
High-risk patients have a 23% incidence of MI, and another 23% will ultimately be diagnosed with unstable angina.
In the absence of ischemic EKG changes or positive cardiac markers, intermediate- and low-risk patients can be
safely managed in a chest pain observation unit for 9 - 12 hours.
In one study, no differences in 30-day outcomes among patients managed with or without stress testing before
discharge were seen. The authors recommend that stress testing be optional for patients with cocaine-associated
chest pain who have had an uneventful 9 - 12 hours of observation.
Patients with cocaine-associated chest pain/ACS should be treated similarly to those with traditional ACS with some
• Cocaine users should be provided with IV benzodiazepines as early management. In the setting of cocaine
use, benzodiazepines relieve chest pain and have beneficial cardiac hemodynamic effects.
• Hypertension and tachycardia may not require direct treatment. Resolution of anxiety with a benzodiazepine
will often lead to resolution of the hypertension and tachycardia. When sedation is not successful,
hypertension can be managed with parenteral agents.
ST-Segment–Elevation Myocardial Infarction
PCI for STEMI is even more desirable in the setting of cocaine use: Case reports document adverse outcomes, such
as a higher rate of ICH, after fibrinolysis in patients who use cocaine.
Careful consideration of the probability of long-term compliance by a patient who abuses cocaine with an antiplatelet
regimen of aspirin and clopidogrel is recommended before a drug-eluting stent is used in a patient with cocaine-
associated MI. In most cases, a bare metal stent would be preferable.
The unopposed α-adrenergic effect by administration of β-blockers leads to worsening coronary vasoconstriction and
increased blood pressure. Multiple experimental models have shown that β-adrenergic antagonists lead to decreased
coronary blood flow, increased seizure frequency, and increased mortality.
The use of the selective β1 antagonist esmolol resulted in significant increases in BP in up to 25% of patients.
The ACC/AHA: "Beta-blockers should not be administered to patients with STEMI precipitated by cocaine use
because of the risk of exacerbating coronary spasm".
Labetalol does not offer any advantages; it is both an α- and β-blocker but has much more β- antagonist effect.
Nitroglycerin - relieves cocaine-associated chest pain; shown to reverse cocaine-associated vasoconstriction.
Calcium Channel Blockers
In ACS unrelated to cocaine use, calcium channel blockers have not demonstrated any beneficial effects on important
outcomes such as survival, however, and in certain subgroups, calcium channel blockers may worsen mortality rates.
The role of calcium channel blockers in the treatment of patients with cocaine-associated ACS is uncertain.
Phentolamine - In cardiac catheterization trials, phentolamine returned coronary arterial diameter to baseline,
suggesting that phentolamine may be useful for the treatment of cocaine-associated ischemia.
Other Therapeutic Agents - It is recommended that aspirin be routinely administered and unfractionated heparin or
LMWH be given to patients with cocaine-associated MI unless there is a contraindication.
Ventricular arrhythmias occurring immediately after cocaine use result from the local anesthetic (sodium channel)
effects on the myocardium. These arrhythmias may respond to the administration of sodium bicarbonate, similar to
arrhythmias associated with other type IA and type IC agents.
Ventricular arrhythmias that occur several hours after the last use of cocaine are usually secondary to ischemia, the
management of which should be the first goal for treatment. Standard management for ventricular arrhythmias,
including lidocaine, is reasonable for persistent or recurrent ventricular arrhythmias.
Discharge Management and Secondary Prevention
Recidivism is high among patients with cocaine-associated chest pain (60% admit to cocaine use in the next year).
Patients with evidence of MI or atherosclerosis should receive long-term antiplatelet therapy with aspirin. In addition to
aspirin, clopidogrel should be given for at least 1 month to patients who undergo PCI with bare metal stents and for at
least 1 year for those treated with drug-eluting stents.
Chronic β-blocker use should be reserved for those with the strongest indications, including those with documented
MI, LV systolic dysfunction, or ventricular arrhythmias, in whom the benefits may outweigh the risks even among
patients at risk for recurrent use of cocaine.
Marik PE, Plante LA. Venous thromboembolic disease and pregnancy. N Engl J Med. Nov
30% of apparently isolated episodes of PE are associated with silent DVT, and in patients presenting with symptoms
of DVT, the frequency of silent PE is 40 - 50%.
The incidence of VTE is 0.76 - 1.72 per 1000 pregnancies, which is 4 times the risk in the nonpregnant population.
Meta-analysis: 2/3 of cases of DVT occur in the antepartum period and are distributed equally among all 3 trimesters.
In contrast, 43 - 60% of pregnancy-related PE occur in the puerperium.
PE is the leading cause of maternal death in the developed world. Current estimates of deaths from PE are 1.1 -
1.5/100,000 deliveries. In the UK, VTE accounts for 1/3 of all maternal deaths.
Risk Factors for Venous Thromboembolism
Pregnancy is thought to be a hypercoagulable state:
• Fibrin generation is increased, fibrinolytic activity is decreased, levels of coagulation factors II, VII, VIII, X are
all increased, free protein S levels are decreased, and acquired resistance to activated protein C is common.
• Uncomplicated pregnancy is accompanied by substantial hemostatic activation as indicated by increased
markers of coagulation activation, such as D-dimer.
• Reduction in venous flow velocity of approximately 50% occurs in the legs by 25 - 29 weeks of gestation and
lasts until approximately 6 weeks after delivery.
• The presence of inherited thrombophilias and the antiphospholipid syndrome, as well as a previous history of
thrombosis, increase the risk for VTE during pregnancy and the postpartum period.
Additional risk factors: black race, heart disease, sickle cell disease, diabetes, lupus, smoking, multiple pregnancy,
age > 35 years, obesity, and cesarean delivery.
There is a marked predisposition for DVT to occur in the left leg (70 - 90% of cases), possibly because of
exacerbation of the compressive effects on the left iliac vein due to its being crossed by the right iliac artery.
The incidence of isolated DVT in the iliac vein is higher in pregnant women. Compression ultrasonography does not
reliably detect iliac DVT.
Heritable Thrombophilia and Venous Thromboembolism
At least 50% of cases of VTE in pregnant women are associated with an inherited or acquired thrombophilia.
Given the rarity of VTE (0.1% of pregnancies) and the high incidence of inherited thrombophilias, universal screening
of pregnant women is not cost-effective. Thrombophilia screening is of limited value in women who have acute VTE
during pregnancy because it does not alter clinical management.
Thrombophilia screening should be considered after the end of pregnancy and once the use of anticoagulant agents
has been stopped, since the results may affect the management of subsequent pregnancies.
Diagnosis of Venous Thromboembolism
VTE is confirmed in < 10% of pregnant women in whom the diagnosis is suspected, as compared with approximately
25% of nonpregnant patients.
Compression ultrasonography - sensitivity = 97% and specificity = 94% for the diagnosis of symptomatic, proximal
DVT in the general population; less accurate for isolated calf- and iliac-vein thrombosis.
During ultrasonography, the need for high pressure to compress the femoral vein in the groin or the absence of flow
on Doppler studies is suggestive of iliac-vein thrombosis.
MR direct thrombus imaging (which does not involve radiation exposure to the fetus) has a high sensitivity and
specificity for the diagnosis of iliac-vein thrombosis.
A pulsed Doppler study of the iliac vein and CT scanning may be useful for detecting iliac-vein thrombosis when MRI
is not available. CT is associated with fetal radiation exposure.
Levels of D-dimer increase with the progression of a normal pregnancy.
One study showed that a negative test with a highly specific assay in the 1st and 2nd trimesters had a negative
predictive value of 100%; the sensitivity and specificity of a positive test were 100% and 60%, respectively.
A negative D-dimer test may be helpful if ultrasonography is normal; a positive D-dimer test requires additional
Patients with suspected PE and normal compression ultrasonography require additional diagnostic imaging:
• A chest x-ray should be obtained to rule out alternative diagnoses.
• V/Q lung scanning or CTPA should be performed:
V/Q scanning delivers a higher fetal dose of radiation than does CTPA; perfusion scanning alone will reduce
the radiation exposure. However, the maternal radiation dose is higher with CTPA than with scintigraphy.
Women with suspected VTE should be advised that V/Q scanning carries a slightly higher risk of childhood
cancer in offspring than does CTPA (1 case in 280,000 vs. <1 in 1 million) but carries a lower risk of maternal
breast cancer (the lifetime risk is up to 13% greater with CTPA than with V/Q scanning).
Management of Venous Thromboembolism during Pregnancy
Unlike warfarin which is containdicated in pregnancy, neither unfractionated heparin nor LMWH crosses the placenta,
and thus there is no possibility of teratogenesis or fetal hemorrhage with these drugs.
LMWH is now preferred, given the reduced risk of bleeding, predictable pharmacokinetics allowing weight-based
dosing without the need for monitoring, and a reduced risk of HIT and heparin-induced osteoporotic fractures.
The management of isolated calf-vein thrombosis is controversial. However, since most iliofemoral thromboses
originate from calf-vein thromboses, anticoagulation is suggested for symptomatic patients.
Retrievable vena caval filters should be considered only for patients in whom anticoagulation is contraindicated or
when extensive VTE develops within 2 weeks before delivery.
Because of increased renal excretion, the half-life of LMWH decreases in pregnancy; consequently, a BID regimen
has been recommended; however, many clinicians use once-daily dosing to simplify administration.
In most patients, monitoring anti-factor Xa activity and making dose adjustments are not required except in patients at
the extremes of body weight and those with altered renal function.
Cutaneous allergic reactions to LMWHs are rare. Experience with fondaparinux suggests that it may be a safe
alternative in women with cross-reactivity among several LMWHs. Limited experience suggests that fondaparinux
crosses the placental barrier, resulting in low but measurable anti–factor Xa activity in umbilical-cord blood. The FDA
has designated fondaparinux as pregnancy category B.
Bed rest is generally not recommended for patients with DVT, except for those with phlegmasia.
Anticoagulant Therapy during Labor and Delivery
If labor occurs in women who have undergone full anticoagulation, neuraxial anesthesia should not be used because
of the risk of spinal hematoma. This issue can be overcome by scheduling elective induction or C-section.
Current guidelines suggest that spinal anesthesia may be performed 12 hours after administration of the last dose of
prophylactic LMWH and 24 hours after the last dose of therapeutic LMWH.
IV unfractionated heparin should be stopped 6 hours before placement of a neuraxial blockade, and a normal aPTT
should be confirmed.
Because of the relatively high chance of cesarean delivery and the difficulty in predicting the onset of labor, many
obstetricians are reluctant to treat a woman with LMWH all the way through her pregnancy, since the agent's effects
cannot be quickly reversed. Patients commonly are switched to SQ UFH for the last few weeks of pregnancy:
However, since the pharmacokinetics and pharmacodynamics of subcutaneous unfractionated heparin are
unpredictable during the 3rd trimester, meticulous monitoring of the aPTT is required.
Furthermore, contrary to popular belief, the pharmacokinetics of subcutaneous unfractionated heparin and
LMWH are quite similar.
These factors, together with the safety concerns regarding the use of UFH, limit the benefit of this approach.
Treatment with LWMH may be resumed within 12 hours after delivery in the absence of persistent bleeding.
Prophylactic LMWH should be delayed for at least 12 hours after the removal of an epidural catheter.
After neuraxial anesthesia, therapeutic LMWH should be administered no earlier than 24 hours postoperatively or post
partum and in the presence of adequate hemostasis
Anticoagulation is recommended for at least 6 weeks post partum and for a total of at least 6 months.
The post-thrombotic syndrome occurs in up to 60% of patients after a DVT. Compression stockings reduce the risk of
this syndrome by about 50% and should be worn on the affected leg for up to 2 years after the acute event.
Thrombolytic therapy may be lifesaving in pregnant patients with massive PE; There is concern that thrombolytic
therapy will lead to placental abruption, but this complication has not been reported.
Although thrombolysis within 10 days after C-section or delivery is contraindicated, successful thrombolysis has been
reported within 1 hour after vaginal delivery and within 12 hours after C-section.
Management of Pulmonary Embolism in Late Pregnancy and Labor
Patients presenting with PE in late pregnancy should be treated with IV heparin. A temporary vena caval filter should
be placed once the diagnosis has been confirmed.
As soon as the patient goes into active labor or a cesarean section is considered, the heparin should be stopped (and
reversed with protamine if necessary).
A C-section should not be performed while the patient is in a fully anticoagulated state; this can lead to uncontrolled
bleeding and maternal death.
The care of the pregnant patient who has massive PE either at term or when suspicion of compromised fetal status
would call for expeditious C-section is complex: management could include cardiopulmonary bypass with
embolectomy followed by C-section or percutaneous mechanical clot fragmentation and placement of an IVC filter.
Thromboprophylaxis during Pregnancy and the Puerperium
Compression stockings are recommended ante partum and post partum for all women who have had a previous VTE.
Postpartum thromboprophylaxis for at least 6 weeks (LMWH or warfarin) is recommended for all women who have
had a previous VTE.
The indications for antepartum pharmacologic prophylaxis are more controversial.
• Pregnant women with > two previous episodes of VTE and those with high-risk thrombophilias (e.g.,
antithrombin deficiency, the antiphospholipid syndrome, factor V Leiden), regardless of whether they have a
history of VTE should receive antenatal thromboprophylaxis.
• Antenatal anticoagulation may not be required for women whose previous venous thromboembolism was not
related to pregnancy and was associated with a risk factor that is no longer present, as long as such women
do not have additional risk factors or thrombophilia.
• For pregnant women with a single idiopathic episode of VTE and for those with a single previous VTE and a
low-risk thrombophilia, antenatal thromboprophylaxis is considered optional.
• Thromboprophylaxis should also be considered for morbidly obese patients and those confined to bed,
particularly if other risk factors are also present.
Thromboprophylaxis after Cesarean Section
The incidence of PE is higher after C-section than after vaginal delivery by a factor of 2.5 - 20, and the incidence of
fatal PE by a factor of 10.
According to a UK registry, > 3/4 postpartum deaths caused by VTE were associated with cesarean delivery.
Recommendations for risk assessment and thromboprophylaxis after C-section:
Low Risk - Early Ambulation: Cesaerean delivery for uncomplicated pregnancy with no other risk factors
Moderate Risk - LMWH or Compression stockings: Age > 35, Obesity, Parity > 3, Gross Varicose Veins,
Preeclampsia, Current Infection, Immobility for > 4 days before operation, Emergency C-section during labor
High Risk - LMWH and Compression stockings: Presence of > 2 risk factors from moderate risk section,
Cesarean hysterctomy, Previous DVT or known thrombophilia
Kelly CP, LaMont JT. Clostridium difficile - more difficult than ever. N Engl J Med. Oct 2008;359(18):1932-
Mid/Late 1990s - reported incidence of C. difficile infection in US acute care hospitals remained stable at 30 - 40
cases/100,000 population. In 2001, this number rose to almost 50.
The rate in 2005 (84 per 100,000) was nearly 3 times the 1996 rate (31 per 100,000).
Emergence of a Virulent Strain
Isolates of a single strain (named NAP-1/027) accounted for over half the isolates from 5 facilities in an outbreak in 6
states, and 82% of stool samples from a severe 2003 Quebec outbreak were positive for the same strain.
3 bacterial factors have been implicated in outbreaks by the virulent NAP-1/027 strain: increased production of toxins
A and B, fluoroquinolone resistance, and production of a toxin termed binary toxin.
C. difficile infection predominantly affects elderly and frail hospital and nursing home patients.
The CDC has warned of a risk of C. difficile infection in populations not previously considered at risk: Young and
previously healthy persons without exposure to a health care environment or antimicrobial therapy.
Close contact with patients who have C. difficile infection was the only evident risk factor in some pediatric cases,
indicating the importance of direct person-to-person spread.
Metronidazole versus Vancomycin
Before 2000, the failure rates for treatment with metronidazole and vancomycin were virtually identical (2.5% and
3.5%, respectively). However, since 2000, much higher failure rates have been reported for metronidazole (18.2%).
A retrospective study reported that the time to resolution of diarrhea in patients who were treated with metronidazole
was significantly longer than in those treated with vancomycin (4.6 vs. 3.0 days).
Several professional societies advocate vancomycin as the first-line agent for patients with severe infection, since a
small increment in efficacy may be critical in patients with fulminant disease.
Recent trial: Compared metronidazole (250 mg QID) with vancomycin (125 mg QID); there was similar efficacy in mild
infection, although the response rate with vancomycin (98%) > metronidazole (90%). In patients with severe infection,
vancomycin was significantly more effective (97% vs. 76%).
Thus, metronidazole is the first-line agent for treatment of mild infection because of its lower cost and concerns about
the proliferation of vancomycin-resistant nosocomial bacteria. Vancomycin is the first-line agent in patients with
severe infection because of more prompt symptom resolution and a significantly lower risk of treatment failure.
Markers of severe C. difficile infection: pseudomembranous colitis, a marked peripheral leukocytosis, acute renal
failure, and hypotension.
Despite its proven superiority, oral vancomycin may not be suitable for some patients with severe infection because of
coexisting ileus or toxic megacolon. IV metronidazole (500 mg QID) is used in this situation and should, if possible, be
supplemented with vancomycin via an NG tube or by enema (500 mg QID).
Passive immunotherapy with IV immunoglobulin has unproven efficacy.
Patients with severe or refractory disease should be evaluated early by a surgeon, since timely subtotal colectomy
can be lifesaving.
Recurrence rates after treatment with metronidazole or vancomycin are similar (20.2% and 18.4%, respectively).
Recurrent infection typically occurs within 4 weeks after the completion of therapy. Resistance to vancomycin in
patients with C. difficile infection has not been reported, and resistance to metronidazole is rare. Recurrence may
result from reinfection with a different strain of C. difficile or persistence of the strain responsible for the initial episode.
Role of Host Immunity
The risk of recurrent C. difficile infection is increased in patients who have already had one recurrence, rising from
20% after an initial episode to 40% after a first recurrence and to > 60% after 2 or more recurrences. This dramatic
escalation in the risk of recurrent infection is related in part to the selection of patients without protective immunity
against C. difficile, which makes them vulnerable to repeated attacks:
C. difficile infection develops in only half the hospitalized patients who become colonized with toxigenic C.
difficile as a complication of antimicrobial therapy, whereas the remainder are symptomless carriers.
After colonization, symptomless carriers manifest an early increase in serum IgG antibodies against toxin A,
whereas patients in whom C. difficile infection develops do not have such increased levels.
In one study, patients with the highest titers of serum IgG antitoxin after antimicrobial therapy were at less risk
for subsequent recurrence by a factor of 44, as compared with those with lower antitoxin titers.
Management of Recurrence
• discontinue all antibiotics and allow the normal bowel microflora to restore itself.
• not all patients in whom recurrent diarrhea develops when they stop taking metronidazole or vancomycin
have recurrent C. difficile infection. Other conditions, such as postinfectious irritable bowel syndrome,
microscopic colitis, and inflammatory bowel disease, may be responsible.
• a positive toxin assay in a patient with minimal or no symptoms should not prompt treatment.
• repeat stool assays are not recommended after therapy, except in patients with moderate or severe diarrhea.
• in patients with persistent diarrhea despite several weeks of treatment with metronidazole or vancomycin,
another cause should be sought, since C. difficile is rarely if ever resistant to metronidazole or vancomycin.
Antibiotics and Probiotics
• A first recurrence of C. difficile infection can be treated with the same agent used to treat the initial episode.
• There is no standard therapy for multiple recurrences. In one study, regimens that incorporated tapering or
pulsed administration of vancomycin resulted in significantly fewer recurrences, with rates of 31% for tapering
and 14% for pulsed administration, as compared with the rate for all other metronidazole or vancomycin
treatments combined (50%).
• Probiotics have shown efficacy in reducing the incidence of simple antibiotic-associated diarrhea, but are
inconsistent in preventing C. difficile infection. Probiotics are not effective as solo therapy for active infection.
Immunotherapy - IV immunoglobulin has been used to treat recurrent infection; no data from randomized, controlled
trials are available. Data regarding the efficacy of active immunization against C. difficile are even more sparse.
Since most cases of C. difficile infection are both iatrogenic and nosocomial, the careful selection of antibiotics and,
whenever possible, the avoidance of their use remain the mainstay of primary prevention. Environmental
decontamination (e.g., with cleaning agents containing at least 5000 ppm available chlorine) and the minimization of
opportunities for cross-infection by hand hygiene and barrier precautions are effective control measures.
Suggested Approaches to Therapy
• Initial Episode & First Recurrence
Mild-to-Moderate Infection: Metronidazole 500 mg TID for 10 -14 days
Severe Infection or Unresponsiveness/Intolerance to Metronidazole: Vancomycin 125 mg QID for 10 - 14 days
• Second Recurrence
Tapered & pulsed Vancomycin: Starting with 125 mg QID for 14 days down to 125 mg every 3 days for 15 days
• Third Recurrence
Vancomycin 125 mg PO QID for 14 days, followed by rifaximin 400 mg BID for 14 days
Edlow JA, Malek AM, Ogilvy CS. Aneurysmal subarachnoid hemorrhage: update for emergency physicians.
J Emerg Med. 2008;34(3):237-251.
Trauma is the leading cause of SAH; ruptured intracranial aneurysms account for 80% of non-traumatic cases. Of the
remaining 20%, half are caused by non-aneurysmal venous “perimesencephalic” hemorrhages. The other 10%
include AV malformations, other vascular lesions, and tumors.
1% of ED headache patients have SAH. Of patients with severe, abrupt-onset headache and normal neurological
examinations, about 10% have SAH.
Roughly 2% of all individuals harbor aneurysms;. Given that the prevalence of aneurysms is 200 times higher than the
annual incidence of SAH, it is clear that most aneurysms do not rupture.
Larger aneurysm size and aspect ratio (dome size/neck size) are independently correlated with risk of rupture.
Surface irregularities or multiple lobes on the aneurysm confer additive risk.
When an aneurysm ruptures, the ICP rises precipitously. Cerebral perfusion may transiently cease, resulting in
unconsciousness, or death.
The mortality rates on the first day and during the first month after hemorrhage are 12% and 40%, respectively.
Hunt and Hess Scale - commonly used, subjective, and has significant inter-observer variability. Scale runs from
Grade 0 (Unruptured) to Grade 5 (deep coma).
World Federation of Neurosurgical Societies (WFNS) SAH grade - more objective; is based on the GCS and presence
or absence of motor deficits.
Peak age at rupture is 50 years.
Important risks for SAH
heavy alcohol use
possibly oral contraception use
family or past personal history of SAH
Cocaine use may also increase the risk in those patients who have aneurysms.
Disorders associated with SAH include autosomal dominant polycystic kidney disease, Ehlers-
Danlos syndrome type IV, and neurofibromatosis type 1.
Misdiagnosis of SAH occurs about 25% of the time. Failure to obtain a CT scan is the most common error.
4 elements of the history best help identify the majority of SAH patients:
• Onset - usually sudden
• Severity - generally “worst of life"
• Quality - comparing with quality of prior headaches is important. Patients usually describe the headache from
SAH as clearly different from prior headaches.
• Associated symptoms - N/V, neck pain, and stiffness are common. However, meningismus may be absent,
especially in the early hours
10% of neurologically normal patients with abrupt-onset, severe, and unusual headaches will have SAH.
• Patients may present with symptoms such as vomiting, fever and headache, mild confusion, or severe neck
pain that suggest other diagnoses such as a viral syndrome, psychiatric disorders, or neck strain.
• Undue focus on associated findings (e.g. abnormal EKG, dysrhythmia, head injury from syncope, elevated
BP) may divert attention from the true cause of the symptoms.
• The headache may improve or resolve with non-narcotic analgesics, including sumatriptan; diagnostic
significance ought not to be ascribed to improvement with medications.
• Headache from warning (or sentinel) bleeds can remit spontaneously. On the other end of the spectrum,
occasional patients with SAH who present with cardiac arrest can have excellent outcomes.
1. Accuracy decays with time, due to circulation of CSF and the resultant dilution and catabolism of the blood.
Studies using 3rd-generation scanners demonstrate sensitivities in the range of 90-98% within the first 24 hrs.
By 3 and 7 days after the ictus, the sensitivity falls to 85% and 50%, respectively.
2. “Spectrum bias” - In alert and awake patients (presumably with smaller volume bleeds), scans are less likely
to show blood.
3. Intracranial blood in anemic patients (HCT < 30%) may be isodense with brain and thus more difficult to see.
4. CT sensitivity studies relied on experienced neuroradiologists’ interpretations; “real world” readings by general
radiologists, neurologists, or emergency physicians are less accurate
False-positive CT for SAH - unusual, but can occur in the settings of IV contrast neurotoxicity, purulent meningitis,
spontaneous intracranial hypotension, isodense subdural hematomas, and diffuse cerebral edema.
Until more convincing data confirm the 100% sensitivity of ultra-early or ultra-modern CT scanning in SAH, all patients
being evaluated for SAH whose CT scans are normal/non-diagnostic, should undergo LP.
Large numbers of RBCs are present in the lumbar theca within 2-4 hrs.
The development of xanthochromia, the yellowish hue resulting from hemoglobin catabolism into oxyhemoglobin,
methemoglobin, and bilirubin, requires more time. Presence of xanthochromia indicates that the CSF contains blood
that has undergone in vivo enzymatic degradation to bilirubin, implying true SAH.
Xanthochromia can be measured visually or by spectrophotometry, the latter being more sensitive. Almost all hospital
labs in North America measure xanthochromia visually. False positives are very common with spectrophotometry.
A recent comparison between the two methods found that of CSF samples that clinicians deemed to be colorless,
none had bilirubin as measured by spectrophotometry.
Xanthochromia takes time to develop. By spectrophotometry, it can take as long as 12 h; however, by visual
inspection, xanthochromia often develops earlier.
To assess for xanthochromia, the CSF should be rapidly centrifuged and (in the case of spectrophotometry) stored in
darkness. When measured visually, the CSF should be carefully compared to an identical tube filled with an equal
volume of tap water against a white background.
Importantly, early-presenting SAH patients without xanthochromia will all have large amounts of RBCs in the CSF.
Distinguishing traumatic taps from true bleeds:
• Look for diminishing numbers of RBCs from the first to the last tube trending toward zero. A simple decrease
is insufficient to exclude SAH and the last tube RBC count should approach zero.
When bloody fluid is identified, wasting 2-3 mL of CSF to increase the gap between the first and last tubes
improves the odds that the last tube RBC count will approach zero. There is no specific number of RBCs that
serves as a threshold amount and the rate of RBC clearance is variable.
• The opening pressure is elevated in 2/3 of SAH patients and is normal in traumatic taps.
Elevated pressure also suggests the alternative diagnosis of cerebral venous sinus thrombosis or idiopathic
intracranial hypertension, and abnormally low pressure suggests spontaneous intracranial hypotension.
Primary Use of CT Angiography for Diagnosis of SAH
A strategy of primary CTA for diagnosis of SAH would be expected to subject many patients to unnecessary work-
ups, procedures, and angiographic contrast material.
MR for Primary Diagnosis of SAH
Although fluid-attenuated inversion recovery (FLAIR) and T2-graded echo MR may be better than CT for detection of
chronic subarachnoid blood and possibly equivalent for intraparenchymal hemorrhage, false positives have been
documented in acute SAH with both techniques.
No large studies of MR diagnosis in unselected headache patients exist. Therefore, CT, which is quicker, cheaper,
more readily available and easier to interpret, is the diagnostic study of choice.
This practice can be dangerous, because an LP in SAH patients may precipitate rebleeding or herniation from an
unrecognized intracranial hematoma, which can occur in the absence of localizing neurological findings. Most such
patients who deteriorated had neck stiffness and were H&H grade 1-3 (mostly 2).
An LP-first strategy is likely safe in selected patients who are neurologically normal and without signs of elevated ICP.
When to Stop the Work-up?
Available evidence strongly suggests that most patients with normal CT and CSF examinations do not require
angiography. The occasional patient whose clinical presentation suggests cranial artery dissection, cerebral venous
sinus thrombosis, or pituitary apoplexy may require further imaging.
“Warning” or “Sentinel” Symptoms
A recent review found that a “warning” or “sentinel” “headache” or “bleed” occurs in 10-43% of cases of SAH.
Most instances likely represent small undiagnosed SAHs. Recall bias may account for a small fraction of cases.
Symptomatic Unruptured Aneurysms
The vast majority of unruptured aneurysms are asymptomatic, but occasional patients have thunderclap headache
from intact aneurysms that are acutely expanding, dissecting, or thrombosing.
Initial Management Considerations
A four-vessel cerebral digital subtraction angiogram usually elucidates the etiology of the SAH. Negative angiograms
occur with perimesencephalic hemorrhage, thrombosed aneurysms, or in cases of severe parent vessel spasm, which
can interfere with aneurysmal filling.
Although DSA remains the gold standard, multi-detector CT angiography demonstrates high sensitivity and specificity.
Other investigators have accumulated experience with MR angiography. Thus, the choice of cerebrovascular imaging
Occurs in 4% of patients in the first 24 h after hemorrhage, and approximately 1.5% per day for up to 2 weeks after
the initial hemorrhage, yielding a total re-hemorrhage rate of 26.5% over the first 2 weeks after the initial bleed.
Those who rebleed have higher H&H grades, larger aneurysms, and worse outcomes. Therefore, strategies to reduce
rebleeding are critical.
Despite a paucity of data, most physicians insert an A-line and use IV agents to maintain adequate cerebral perfusion
in the patient with elevated ICP and in elderly patients with pre-existing atherosclerosis or HTN. The most common
anti-hypertensive agents used are labetolol, nicardipine, and nitroprusside.
A recent review found that antifibrinolytics are not routinely indicated because the price for the reduction in rebleeding
was increased ischemic deficits from vasospasm. However, there has been renewed interest in using short-term
antifibrinolytics from the time of diagnosis to the time of definitive treatment, even if this interval is only several hours.