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Hyperkalemia (hyper- high; kalium, potassium; -emia, "in the blood") is an elevated blood level

of the electrolyte potassium. Extreme hyperkalemia is a medical emergency due to the

risk of potentially fatal abnormal heart rhythms (arrhythmia).

Signs and symptoms

Symptoms are fairly nonspecific and generally include malaise, palpitations and muscle weakness; mild

hyperventilation may indicate a compensatory response to metabolic acidosis, which is one of the possible

causes of hyperkalemia. Often, however, the problem is detected during screening blood tests for a

medical disorder, or it only comes to medical attention after complications have developed, such

as cardiac arrhythmia or sudden death.

During the medical history taking, a physician will dwell on kidney disease and medication use (see

below), as these are the main causes. The combination of abdominal

pain, hypoglycemia and hyperpigmentation, often in the context of a history of other autoimmune

disorders, may be signs of Addison's disease, itself a medical emergency.


In order to gather enough information for diagnosis, the measurement of potassium needs to be repeated,

as the elevation can be due to hemolysis in the first sample. The normal serum level of potassium is 3.5 to

5 mEq/L. Generally, blood tests for renal function (creatinine, blood urea nitrogen), glucose and

occasionally creatine kinase andcortisol will be performed. Calculating the trans-tubular potassium

gradient can sometimes help in distinguishing the cause of the hyperkalemia.

In many cases, renal ultrasound will be performed, since hyperkalemia is highly suggestive of renal


Also, electrocardiography (EKG/ECG) may be performed to determine if there is a significant risk of

cardiacarrhythmias (see ECG/EKG Findings, below).

Differential diagnosis

Causes include:

Ineffective elimination from the body

 Renal insufficiency

 Medication that interferes with urinary excretion:

 ACE inhibitors and angiotensin receptor blockers

 Potassium-sparing diuretics (e.g. amiloride and spironolactone)

 NSAIDs such as ibuprofen, naproxen, or celecoxib

 The calcineurin inhibitor immunosuppressants ciclosporin and tacrolimus

 The antibiotic trimethoprim

 The antiparasitic drug pentamidine

 Mineralocorticoid deficiency or resistance, such as:

 Addison's disease

 Aldosterone deficiency, including reduced levels due to the blood thinner, heparin

 Some forms of congenital adrenal hyperplasia

 Type IV renal tubular acidosis (resistance of renal tubules to aldosterone)

 Gordon's syndrome (“familial hypertension with hyperkalemia”), a rare genetic disorder caused

by defective modulators of salt transporters, including the thiazide-sensitive Na-Cl cotransporter.

Excessive release from cells

 Rhabdomyolysis, burns or any cause of rapid tissue necrosis, including tumor lysis syndrome

 Massive blood transfusion or massive hemolysis

 Shifts/transport out of cells caused by acidosis, low insulin levels, beta-

blocker therapy, digoxin overdose, or the paralyzing anesthetic succinylcholine

Excessive intake

 Intoxication with salt-substitute, potassium-containing dietary supplements, or potassium

chloride (KCl) infusion. Note that for a person with normal kidney function and nothing interfering

with normal elimination (see above), hyperkalemia by potassium intoxication would be seen only with

large infusions of KCl or oral doses of several hundred millequivalents of KCl.[1]

Lethal injection

Hyperkalemia is intentionally brought about in an execution by lethal injection, with potassium

chloride being the third and last of the three drugs administered to cause death.


Pseudohyperkalemia is a rise in the amount of potassium that occurs due to excessive leakage of

potassium from cells, during or after blood is drawn. It is a laboratory artifact rather than a biological

abnormality and can be misleading to caregivers.[2] Pseudohyperkalemia is typically caused

by hemolysis during venipuncture (by either excessive vacuum of the blood draw or by a collection needle

that is of too fine a gauge); excessive tournequet time or fist clenching during phlebotomy (which

presumably leads to efflux of potassium from the muscle cells into the bloodstream);[3] or by a delay in

the processing of the blood specimen. It can also occur in specimens from patients with abnormally high

numbers of platelets (>1,000,000/mm³), leukocytes (> 100 000/mm³), or erythrocytes (hematocrit >
55%). People with "leakier" cell membranes have been found, whose blood must be separated

immediately to avoid pseudohyperkalemia.[4]


Potassium is the most abundant intracellular cation. It is critically important for many physiologic

processes, including maintenance of cellular membrane potential, homeostasis of cell volume, and

transmission of action potentials in nerve cells. Its main dietary sources

are vegetables (tomato and potato), fruits (orange and banana) and meat. Elimination is through

the gastrointestinal tract and the kidney.

The renal elimination of potassium is passive (through the glomeruli), and resorption is active in

the proximal tubule and the ascending limb of the loop of Henle. There is active excretion of potassium in

the distal tubule and the collecting duct; both are controlled by aldosterone.

Hyperkalemia develops when there is excessive production (oral intake, tissue breakdown) or ineffective

elimination of potassium. Ineffective elimination can be hormonal (in aldosterone deficiency) or due to

causes in the renal parenchyma that impair excretion.

Increased extracellular potassium levels result in depolarization of the membrane potentials of cells. This

depolarization opens some voltage-gated sodium channels, but not enough to generate an action

potential. After a short while, the open sodium channels inactivate and become refractory, increasing the

threshold to generate an action potential. This leads to the impairment of neuromuscular, cardiac,

and gastrointestinal organ systems. Of most concern is the impairment of cardiac conduction which can

result in ventricular fibrillation or asystole.

During extreme exercise, potassium is released from active muscle and the serum potassium rises to a

point that would be dangerous at rest. For unclear reasons, it appears as if the high levels of adrenaline

and noradrenaline have a protective effect on the cardiac electrophysiology.[5]

Patients with the rare hereditary condition of hyperkalemic periodic paralysis appear to have a heightened

sensitivity of muscular symptoms that are associated with transient elevation of potassium levels.

Episodes of muscle weakness and spasms can be precipitated by exercise or fasting in these subjects.

ECG findings

With mild to moderate hyperkalemia, there is reduction of the size of the P wave and development of

peaked T waves. Severe hyperkalemia results in a widening of the QRS complex, and the EKG complex

can evolve to a sinusoidalshape. There appears to be a direct effect of elevated potassium on some of the

potassium channels that increases their activity and speeds membrane repolarization. Also, (as

noted above), hyperkalemia causes an overall membrane depolarization that inactivates many sodium

channels. The faster repolarization of the cardiac action potential causes the tenting of the T waves, and
the inactivation of sodium channels causes a sluggish conduction of the electrical wave around the heart,

which leads to smaller P waves and widening of the QRS complex.

The serum K+ concentration at which electrocardiographic changes develop is somewhat variable.[6]

Although the factors influencing the effect of serum potassium levels on cardiac electrophysiology are

not entirely understood, the concentrations of other electrolytes, as well as levels of catecholamines, play

a major role.[8][9]


Acute: When arrhythmias occur, or when potassium levels exceed 6.5 mmol/l, emergency lowering of

potassium levels is mandated. Several agents are used to lower K levels. Choice depends on the degree

and cause of the hyperkalemia, and other aspects of the patient's condition.

 Calcium supplementation (calcium gluconate 10% (10ml), preferably through a central venous

catheter as the calcium may cause phlebitis) does not lower potassium but

decreases myocardial excitability, protecting against life threatening arrhythmias.

 Insulin (e.g. intravenous injection of 10-15u of regular insulin {along with 50ml of 50% dextrose

to prevent hypoglycemia}) will lead to a shift of potassium ions into cells, secondary to increased

activity of the sodium-potassium ATPase.

 Bicarbonate therapy (e.g. 1 ampule (45mEq) infused over 5 minutes) is effective in cases of

metabolic acidosis. The bicarbonate ion will stimulate an exchange of cellular H+ for Na+, thus leading

to stimulation of the sodium-potassium ATPase.

 Salbutamol (albuterol, Ventolin) is a β2-selective catecholamine that is administered by nebulizer

(e.g. 10–20 mg). This drug promotes movement of K into cells, lowering the blood levels.

 Refractory or severe cases may need dialysis to remove the potassium from the circulation.


 Preventing recurrence of hyperkalemia typically involves reduction of dietary potassium, removal

of an offending medication, and/or the addition of a diuretic (such as furosemide (Lasix)

or hydrochlorothiazide).

 Polystyrene sulfonate (Calcium Resonium, Kayexalate) is a binding resin that binds K within the

intestine and removes it from the body by defecation. Calcium Resonium (15g three times a day in

water) can be given by mouth. Kayexelate (30g) can be given by mouth or as an enema. In both

cases, the resin absorbs K within the intestine and carries it out of the body by defecation. This

medication may cause diarrhea.

2.) Acute myocardial infarction: The term "myocardial infarction" focuses on the heart muscle, which
is called themyocardium,and the changes that occur in it due to the sudden deprivation of circulating
blood. This is usually caused by arteriosclerosis with narrowing of the coronary arteries, the culminating
event being a thrombosis (clot). The main change is death (necrosis) of myocardial tissue.

The word "infarction" comes from the Latin "infarcire" meaning "to plug up or cram." It refers to the
clogging of the artery, which is frequently initiated by cholesterol piling up on the inner wall of the blood
vessels that distribute blood to the heart muscle.

Definition and causes

Acute myocardial infarction (MI) is defined as death or necrosis of myocardial cells. It is a diagnosis at the

end of the spectrum of myocardial ischemia or acute coronary syndromes. Myocardial infarction occurs

when myocardial ischemia exceeds a critical threshold and overwhelms myocardial cellular repair

mechanisms designed to maintain normal operating function and hemostasis. Ischemia at this critical

threshold level for an extended period results in irreversible myocardial cell damage or death.

Critical myocardial ischemia may occur as a result of increased myocardial metabolic demand, decreased

delivery of oxygen and nutrients to the myocardium via the coronary circulation, or both. An interruption

in the supply of myocardial oxygen and nutrients occurs when a thrombus is superimposed on an

ulcerated or unstable atherosclerotic plaque and results in coronary occlusion. A high-grade (more than

75%) fixed coronary artery stenosis caused by atherosclerosis or a dynamic stenosis associated with

coronary vasospasm can also limit the supply of oxygen and nutrients and precipitate an MI. Conditions

associated with increased myocardial metabolic demand include extremes of physical exertion, severe

hypertension (including forms of hypertrophic obstructive cardiomyopathy), and severe aortic valve

stenosis. Other cardiac valvular pathologies and low cardiac output states associated with a decreased

aortic diastolic pressure, which is the prime component of coronary perfusion pressure, can also

precipitate MI.

Myocardial infarction can be subcategorized on the basis of anatomic, morphologic, and diagnostic clinical

information. From an anatomic or morphologic standpoint, the two types of MI are transmural and

nontransmural. A transmural MI is characterized by ischemic necrosis of the full thickness of the affected

muscle segment(s), extending from the endocardium through the myocardium to the epicardium. A

nontransmural MI is defined as an area of ischemic necrosis that does not extend through the full

thickness of myocardial wall segment(s). In a nontransmural MI, the area of ischemic necrosis is limited to

the endocardium or endocardium and myocardium. It is the endocardial and subendocardial zones of the

myocardial wall segment that are the least perfused regions of the heart and the most vulnerable to

conditions of ischemia. An older subclassification of MI, based on clinical diagnostic criteria, is determined
by the presence or absence of Q waves on an electrocardiogram (ECG). However, the presence or absence

of Q waves does not distinguish a transmural from a nontransmural MI, as determined by pathology. 1

A more common clinical diagnostic classification scheme is also based on electrocardiographic findings as

a means of distinguishing between two types of MI, one that is marked by ST elevation (STEMI) and one

that is not (NSTEMI). Management practice guidelines often distinguish between STEMI and non-STEMI,

as do many of the studies on which recommendations are based. The distinction between an STEMI and

NSTEMI also does not distinguish a transmural from a nontransmural MI. The presence of Q waves or ST-

segment elevation is associated with higher early mortality and morbidity; however, the absence of these

two findings does not confer better long-term mortality and morbidity. 1


Myocardial infarction is the leading cause of death in the United States and in most industrialized nations

throughout the world. Approximately 800,000 people in the United States are affected and, in spite of a

better awareness of manifesting symptoms, 250,000 die before presentation to a hospital. 1 The survival

rate for U.S. patients hospitalized with MI is approximately 90% to 95%. This represents a significant

improvement in survival and is related to improvements in emergency medical response and treatment


MI can occur at any age, but its incidence rises with age. The actual incidence is dependent on

predisposing risk factors for atherosclerosis (see later). Approximately 50% of all MIs in the United States

occur in people younger than 65 years. However, in the future, as demographics shift and the mean age

of the population increases, a larger percentage of patients presenting with MI will be older than 65

years. 1

Risk factors

Six primary risk factors have been identified with the development of atherosclerotic coronary artery

disease and MI—hyperlipidemia, diabetes mellitus, hypertension, smoking, male gender, and family

history of atherosclerotic arterial disease. The presence of any risk factor is associated with doubling the

relative risk of developing atherosclerotic coronary artery disease. 1

High Blood Cholesterol Level.

An elevated level of total cholesterol is associated with an increased risk of coronary atherosclerosis and

MI. Laboratory testing provides a measure of certain types of circulating fat particles. Elevated levels of

low-density lipoprotein (LDL) cholesterol are associated with an increased incidence of atherosclerosis and

MI. A full summary of the National Heart, Lung, and Blood Institute's cholesterol guidelines is available

online and includes a free Palm OS software download for point of care use. 2
Diabetes Mellitus.

Diabetics have a substantially greater risk of atherosclerotic vascular disease in the heart as well as in

other areas of their vasculature. Diabetes increases the risk of MI because it increases the rate of

atherosclerotic progression and adversely affects blood cholesterol levels. This accelerated form of

atherosclerosis occurs regardless of whether a patient has insulin- or noninsulin-dependent diabetes.


High blood pressure (BP) has consistently been associated with an increased risk of MI. This risk is

associated with systolic and diastolic hypertension. The control of hypertension with appropriate

medication has been shown to reduce the risk of MI significantly. A full summary of the National Heart,

Lung, and Blood Institute's JNC VI guidelines is available online. 3

Tobacco Use.

Certain components of tobacco and tobacco combustion gases are known to damage blood vessel walls.

The body's response to this type of injury elicits the formation of atherosclerosis and its progression,

thereby increasing the risk of MI. The American Lung Association maintains a website with updates on the

public health initiative to reduce tobacco use and is a resource for smoking cessation strategies for

patients and health care providers. Other public and private sources of smoking cessation information are

also available online.

Male Gender.

The incidence of atherosclerotic vascular disease and MI is higher in men than women in all age groups.

This gender difference in MI incidence, however, narrows with increasing age.

Family History.

A family history of premature coronary disease increases an individual's risk of atherosclerosis and MI. The

cause of familial coronary events is multifactorial and includes other elements, such as genetic

components and acquired general health practices (e.g., smoking, high-fat diet).


Mechanisms of Occlusion

Most MIs are caused by a disruption in the vascular endothelium associated with an unstable

atherosclerotic plaque that stimulates the formation of an intracoronary thrombus, which results in

coronary artery blood flow occlusion. If such an occlusion persists long enough (20 to 40 minutes),

irreversible myocardial cell damage and cell death will occur.

The development of atherosclerotic plaque occurs over a period of years to decades. The initial vascular

lesion leading to the development of atherosclerotic plaque is not known with certainty. The two primary

characteristics of the clinically symptomatic atherosclerotic plaque are a fibromuscular cap and an

underlying lipid-rich core. Plaque erosion may occur because of the actions of metalloproteases and the

release of other collagenases and proteases in the plaque, which result in thinning of the overlying

fibromuscular cap. The action of proteases, in addition to hemodynamic forces applied to the arterial

segment, can lead to a disruption of the endothelium and fissuring or rupture of the fibromuscular cap.

The degree of disruption of the overlying endothelium can range from minor erosion to extensive fissuring,

which results in an ulceration of the plaque. The loss of structural stability of a plaque often occurs at the

juncture of the fibromuscular cap and the vessel wall, a site otherwise known as the plaque's “shoulder

region.” Disruption of the endothelial surface can cause the formation of thrombus via platelet-mediated

activation of the coagulation cascade. If a thrombus is large enough to occlude coronary blood flow

completely for a sufficient period, MI can result.

Mechanisms of Myocardial Damage

The severity of an MI is dependent on three factors: (1) the level of the occlusion in the coronary artery;

(2) the length of time of the occlusion; and (3) the presence or absence of collateral circulation. Generally,

the more proximal the coronary occlusion, the more extensive the amount of myocardium at risk of

necrosis. The larger the MI, the greater the chance of death because of a mechanical complication or

pump failure. The longer the period of vessel occlusion, the greater the chances of irreversible myocardial

damage distal to the occlusion.

The death of myocardial cells first occurs in the area of myocardium most distal to the arterial blood

supply—that is, the endocardium. As the duration of the occlusion increases, the area of myocardial cell

death enlarges, extending from the endocardium to the myocardium and ultimately to the epicardium. The

area of myocardial cell death then spreads laterally to areas of watershed or collateral perfusion.

Generally, after a 6- to 8-hour period of coronary occlusion, most of the distal myocardium has died. The

extent of myocardial cell death defines the magnitude of the MI. If blood flow can be restored to at-risk

myocardium, more heart muscle can be saved from irreversible damage or death.

Signs and symptoms

Acute MI may have unique manifestations in individual patients. The degree of symptoms ranges from

none at all to sudden cardiac death. An asymptomatic MI is not necessarily less severe than a

symptomatic event but patients who experience asymptomatic MIs are more likely to be diabetic. Despite

the diversity of manifesting symptoms of MI, there are some characteristic symptoms (Box 1).

Box 1: Signs and Symptoms of a Myocardial Infarction

Chest pain described as a pressure sensation, fullness, or squeezing in the midportion of the thorax
Radiation of chest pain into the jaw or teeth, shoulder, arm, and/or back

Associated dyspnea or shortness of breath

Associated epigastric discomfort with or without nausea and vomiting

Associated diaphoresis or sweating

Syncope or near-syncope without other cause

Impairment of cognitive function without other cause

An MI may occur at any time of the day, but most appear to be clustered around the early hours of the

morning, are associated with demanding physical activity, or both. Approximately 50% of patients have

some warning symptoms (angina pectoris or an anginal equivalent) before the infarct.


Identifying a patient who is currently experiencing a MI can be extremely straightforward, difficult, or

somewhere in between. A straightforward diagnosis of MI can usually be made in patients who have a

number of atherosclerotic risk factors along with the presence of symptoms consistent with a lack of blood

flow to the heart. Patients who suspect that they are having a MI usually present to an emergency

department. Once a patient's clinical picture raises a suspicion of a MI, several confirmatory tests can be

performed rapidly. These tests include electrocardiography, blood testing, and echocardiography.


The first test is electrocardiography, which may demonstrate that a MI is in progress or has already

occurred (Fig. 1). Interpretation of an ECG is beyond the scope of this chapter. However, one feature of

the ECG in a patient with an MI should be noted because it has a bearing on management. Practice

guidelines on MI management consider patients whose ECG does or does not show ST-segment elevation

separately. As noted earlier, the former is referred to as STEMI (ST-elevation MI) and the latter as

NSTEMI (non–ST-elevation MI).

Blood Tests

Living heart cells contain enzymes and proteins (e.g., creatine phosphokinase, troponin, myoglobin) within

cell membranes associated with specialized cellular functions such as contraction. When a heart muscle

dies, cellular membranes lose integrity and intracellular enzymes and proteins slowly leak into the
bloodstream. These enzymes and proteins can be detected by a blood sample analysis. The concentration

of enzymes in a blood sample—and more importantly, the changes in concentration found in samples

taken over time—correlate with the amount of heart muscle that has died ( Table 1 ).
Table 1: Normal Values of Blood Tests to Detect Myocardial Infarction

Analyte Normal Range

Total creatinine phosphokinase (CPK) 30-200 U/L

CK, MB fraction 0.0-8.8 ng/mL

CK, MB fraction (% of total CPK) 0-4%

CK, MB2 fraction <1 U/L

Troponin I 0.0-0.4 ng/mL

Troponin T 0.0-0.1 ng/mL


An echocardiogram may be performed to compare areas of the left ventricle that are contracting normally

with those that are not. One of the earliest protective actions of myocardial cells used during limited blood

flow is to turn off the energy-requiring mechanism for contraction, this mechanism begins within minutes

after normal blood flow is interrupted. The echocardiogram can be helpful in identifying which portion of

the heart is affected by a MI and which of the coronary arteries is most likely to be occluded.

Unfortunately, the presence of wall motion abnormalities on the echocardiogram may be the result of an

acute MI or previous (old) MI or other myopathic processes. Thus, the usefulness of echocardiography for

the diagnosis of MI is limited.


The goals of therapy in AMI are the expedient restoration of normal coronary blood flow and the maximum

salvage of functional myocardium. These goals can be met by a number of medical interventions and

adjunctive therapies. The primary obstacles to achieving these goals are the patient's failure to recognize

MI symptoms quickly and the delay in seeking medical attention. When patients present to a hospital,

there are a variety of interventions to achieve treatment goals. “Time is muscle” guides the management

decisions in MI. Table 2 provides detailed information about the MI interventions for which there is

substantial agreement and the timing.

Table 2: Management Goals for ST-Elevation Myocardial Infarction (STEMI) and Non–ST-
Elevation Myocardial Infarction (NSTEMI)

Acute MI Acute MI
Intervention Timing Comments

Aspirin * At or before arrival

Beta blocker † At arrival Some contraindications

Fibrinolytic therapy Also for LBBB

Fibrinolytic therapy At arrival, within 30 min Also for LBBB

Coronary Within 90 min after Also for LBBB (in facilities so

angiography, arrival equipped)


Reperfusion Within 12 hr of onset of


LDL cholesterol During hospital stay Unless recently done


Aspirin * Prescribe at discharge

Beta blocker Prescribed at discharge

Lipid-lowering agent Prescribe at discharge

ACEI or ARB Prescribe at discharge

Smoking cessation During hospitalization


* For medications, only use if no contraindication or sensitivity.

†Consider risks and benefits of beta blockers if patient has beta blocker allergy, bradycardia at admission

or within 24 hours, heart failure at admission or within 24 hours; second- or third-degree heart block;

shock at admission or within 24 hours.

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; LBBB, left bundle

branch block; LDL, low-density lipoprotein.

Medical Treatment

The use of aspirin has been shown to reduce mortality from MI. Aspirin in a dose of at least 160 mg and

up to 325 mg should be administered immediately on recognition of MI signs and symptoms and

continued daily indefinitely. 1 The nidus of an occlusive coronary thrombus is the adhesion of a small

collection of activated platelets at the site of intimal disruption in an unstable atherosclerotic plaque.

Aspirin interferes with function of the enzyme cyclooxygenase and inhibits the formation of thromboxane

A2. Within minutes, aspirin prevents additional platelet activation and interferes with platelet adhesion and

cohesion. This effect benefits all patients with acute coronary syndromes, including those with an MI.

Aspirin alone has one of the greatest impacts on the reduction of MI mortality. Its beneficial effect is
observed early in therapy and persists for years with continued use. The long-term benefit is sustained,

even at doses as low as 75 mg/day. 1

Other antiplatelet agents, including clopidogrel, ticlopidine, and dipyridamole, have not been shown in any

large-scale trial to be superior to aspirin for MI. These other antiplatelet agents, specifically clopidogrel,

may be useful for patients who have a true allergy to aspirin and for patients with known resistance to

aspirin's effects.

Supplemental Oxygen

Supplemental oxygen should be administered to patients with symptoms and/or signs of pulmonary

edema or pulse oximetry, less than 90% blood oxygen saturation. 1 The rationale for use is the assurance

that erythrocytes will be saturated to maximum carrying capacity. Because MI impairs the circulatory

function of the heart, oxygen extraction by the heart and by other tissues may be diminished. In some

cases, elevated pulmonary capillary pressure and pulmonary edema can decrease oxygen uptake as a

result of impaired pulmonary alveolar-capillary diffusion. Supplemental oxygen increases the driving

gradient for oxygen uptake.

Arterial blood that is at its maximum oxygen-carrying capacity can potentially deliver oxygen to

myocardium in jeopardy during an MI via the collateral coronary circulation. The recommended duration of

supplemental oxygen administration in a MI is 2 to 6 hours, longer if congestive heart failure occurs or

arterial oxygen saturation is less than 90%. Despite this, however, there are no published studies

demonstrating that oxygen therapy reduces the mortality or morbidity of an MI.


Intravenous nitrates should be administered to patients with MI and congestive heart failure, persistent

ischemia, hypertension, or large anterior wall MI. 1 The primary benefit of nitrates is derived from its

vasodilator effect. Nitrates are metabolized to nitric oxide in the vascular endothelium. Nitric oxide relaxes

vascular smooth muscle and dilates the blood vessel lumen. Vasodilation reduces cardiac preload and

afterload and decreases the myocardial oxygen requirements needed for circulation at a fixed flow rate.

Vasodilation of the coronary arteries improves blood flow through the partially obstructed vessels, as well

as through collateral vessels. Nitrates can reverse the vasoconstriction associated with thrombosis and

coronary occlusion. 1

When administered sublingually or intravenously, nitroglycerin has a rapid onset of action. Clinical trial

data have supported the initial use of nitroglycerin for up to 48 hours in MI. There is little evidence that

nitroglycerin provides substantive benefit as long-term post-MI therapy, except when severe pump

dysfunction or residual ischemia is present. Low BP, headache, and tachyphylaxis limit the use of

nitroglycerin. Nitrate tolerance can be overcome by increasing the dose or by providing a daily nitrate-free

interval of 8 to 12 hours ( Table 3 ). 1

Table 3: Nitroglycerin Dosage Schedule in Myocardial Infarction

Nitroglycerin Formulation Dosage

Sublingual tablet 0.2-0.6 mg every 5 min

Spray 0.4 mg every 5 min

Transdermal or paste 0.2-0.8 mg/hr

Intravenous 5.0-200 mcg/min

Pain Control Agents

Pain from MI is often intense and requires prompt and adequate analgesia. The agent of choice is

morphine sulfate, given initially IV at 5- to 15-minute intervals. Typical doses are 2 to 4 mg, with

increments of 2 to 8 mg. 1 Reduction in myocardial ischemia also serves to reduce pain, so oxygen

therapy, nitrates, and β-blocker therapy complement morphine.

Beta Blockers

Beta blocker therapy is recommended within 12 hours of MI symptoms and is continued indefinitely.

Treatment with a beta blocker decreases the incidence of ventricular arrhythmias, recurrent ischemia,

reinfarction and, if given early enough, infarct size and short-term mortality. 5 Beta blockade decreases the

rate and force of myocardial contraction and decreases overall myocardial oxygen demand. In the setting

of reduced oxygen supply in MI, the reduction in oxygen demand provided by beta blockade minimizes

myocardial injury and death.

The use of a beta blocker has a number of recognized adverse effects. The most serious are heart failure,

bradycardia, and bronchospasm. Even so, the benefits in reducing both mortality and the risk of

reinfarction are so great that there are no absolute contraindications to beta blocker use in MI. During the

acute phase of an MI, beta blocker therapy may be initiated intravenously; later, patients can switch to

oral therapy for long-term treatment ( Table 4 ). 1

Table 4: Selective Beta1 Blockers

Beta1 Blocker Dosage

Metoprolol 25-200 mg every 12 hr

Atenolol 25-200 mg every 24 hr

Esmolol 50-300 μg/kg/min IV

Betaxolol 5-20 mg every 24 hr

Bisoprolol 5-20 mg every 24 hr

Acebutolol 200-600 mg every 12 hr
Unfractionated Heparin.

This is not used routinely for MI—for example, for uncomplicated NSTEMI. IV unfractionated heparin is

recommended for patients with an MI who undergo percutaneous revascularization or fibrinolytic therapy

with alteplase. IV unfractionated heparin is also recommended for patients with an MI who receive

fibrinolytic therapy with a nonselective fibrinolytic agent (e.g., urokinase, streptokinase, anistreplase) and

are at increased risk for systemic emboli because of a prior embolic event, large or anterior wall infarction,

known left ventricular thrombus, or atrial fibrillation. 1

Unfractionated heparin is beneficial until the inciting thrombotic cause (ruptured plaque) has completely

resolved or healed. Unfractionated heparin has been shown to be effective when administered

intravenously or subcutaneously according to specific guidelines. The minimum duration of heparin

therapy post-MI generally is 48 hours, but may be longer, depending on the individual clinical scenario.

Low-Molecular-Weight Heparin.

Low-molecular-weight heparin (LMWH) can be administered to MI patients not treated with fibrinolytic

therapy who have no contraindications to heparin. 1 The LMWH class of drugs includes several agents that

have distinctly different anticoagulant effects. LMWHs have been proved to be effective for treating acute

coronary syndromes characterized by unstable angina and non–Q wave MI. Their fixed doses are easy to

administer, and laboratory testing to measure their therapeutic effect is not necessary. On the other hand,

the absence of monitoring currently remains an obstacle to the more widespread use of LMWHs in MI

patients who might require percutaneous or surgical revascularization ( Table 5 ). 1

Table 5: Heparin Dosage

Type of Heparin Dosage

Unfractionated 60-70 U/kg IV load (max, 5000 U); 12-15 U/kg/hr IV maintenance drip; nomogram—

heparin titrate to maintain aPTT 1.5-2.5 × control

Enoxaparin 1 mg/kg subcutaneously every 12 hr

Dalteparin 120 IU/kg subcutaneously every 12 hr (max, 10,000IU in 24hr)

aPTT, activated partial thromboplastin time.

© 2002 The Cleveland Clinic Foundation.


Fibrinolytic therapy is indicated for patients with a suspected MI, especially for STEMI or NSTEMI with left

bundle branch block. 5 Therapy should be started within 30 minutes of hospital arrival. 1,5 Fibrinolytic

therapy is especially important in health care facilities that cannot mount a rapid coronary catheterization

intervention. Restoration of coronary blood flow in MI patients can be accomplished pharmacologically with

the use of a fibrinolytic agent. As a class, the plasminogen activators have been shown to restore coronary
blood flow in 50% to 80% of MI patients. The successful use of fibrinolytic agents provides a definite

survival benefit that is maintained for years. A randomized controlled trial has established that an

accelerated alteplase-heparin regimen is superior to two streptokinase-heparin regimens. Reteplase has

been shown to produce slightly higher 60- and 90-minute angiographic patency rates than accelerated

alteplase, although adverse event rates were equal. However, the better early patency rate did not

translate into any survival advantage at 30 days follow-up. The most critical variable in achieving

successful fibrinolysis is time from symptom onset to drug administration. A fibrinolytic is most effective

when the door to needle time is 30 minutes or less ( Table 6 ). 1

Table 6: Fibrinolytic Therapy for Myocardial Infarction

Patency at 90
Agent Dosage

Alteplase (Activase) Body weight > 67 kg: 15-mg loading dose + 50 mg/30 min + 35 75%

mg/60 min IV

Body weight < 67 kg: 15-mg loading dose + 0.75 mg/kg/30 min

(<50 mg total) + 0.5 mg/kg/60 min (<35 mg total)

Reteplase 10 U over 2 min; wait 30 min; 10 U/2 min IV 75%


Streptokinase 1,500,000 U over 60 min IV 50%


© 2002 The Cleveland Clinic Foundation.

Glycoprotein IIb/IIIa Antagonists

Glycoprotein IIb/IIIa receptors on platelets bind to fibrinogen in the final common pathway of platelet

aggregation. Antagonists to glycoprotein IIb/IIIa receptors are potent inhibitors of platelet aggregation.

The use of IV glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention (PCI) and in

patients with MI and acute coronary syndromes has been shown to reduce the composite end point of

death, reinfarction, and the need for target lesion revascularization at follow-up ( Table 7 ).
Table 7: Glycoprotein Ilb/IIa Inhibitors

Agent Use(s) Dosage

Abciximab Coronary intervention 0.25 mg/kg IV loading dose; 0.125 mcg/kg/min IV

maintenance (max, 10 mcg/min); duration of infusion, 12-24


Eptifibatide Acute coronary syndrome; 180 mcg/kg IV loading dose; 2.0 mcg/kg/min IV maintenance;

coronary intervention duration of infusion, up to 72 hr

Tirofiban Acute coronary syndrome; 0.4 mcg/kg/min x 30 min IV loading dose; 0.1 mcg/kg/min IV
coronary intervention maintenance; duration of infusion, 12-24 hr

© 2002 The Cleveland Clinic Foundation.

Other Treatment Options
Percutaneous Coronary Intervention

Patients with STEMI or MI with left bundle branch block should have PCI within 90 minutes of arrival at

the hospital if skilled cardiac catheterization services are available. 1,5 PCI consists of diagnostic

angiography combined with angioplasty and, frequently, stenting. It is well established that emergency

PCI is more effective than fibrinolytic therapy in centers in which PCI can be performed by experienced

personnel in a timely fashion. 5 An operator is considered experienced with more than 75 interventional

procedures per year. 1,5 A well-equipped catheterization laboratory with experienced personnel performs

more than 200 interventional procedures per year and has surgical backup available. As noted earlier,

centers that are unable to provide such support should consider administering fibrinolytic therapy as their

primary MI treatment. 5

Restoration of coronary blood flow in a MI can be accomplished mechanically by PCI. Mechanical

revascularization by PCI is used as a primary therapy in many well-equipped medical centers and as an

alternative to fibrinolysis when fibrinolysis is not clearly indicated or contraindicated. PCI can successfully

restore coronary blood flow in 90% to 95% of MI patients. Several studies have demonstrated that PCI

has an advantage over fibrinolysis with respect to short-term mortality, bleeding rates, and reinfarction

rates. However, the short-term mortality advantage is not durable, and PCI and fibrinolysis appear to yield

similar survival rates over the long term. PCI provides a definite survival advantage over fibrinolysis for MI

patients who are in cardiogenic shock. 1

The use of stents with PCI for MI is superior to the use of PCI without stents, primarily because stenting

reduces the need for subsequent target vessel revascularization. Any advantage that PCI has over

fibrinolytic therapy is predicated on a rapid restoration (less than 90 minutes) of coronary blood flow. PCI

re-establishes brisk flow in more than 90% of patients.

Surgical Revascularization

Emergent or urgent coronary artery bypass grafting (CABG) is warranted in the setting of failed PCI in

patients with hemodynamic instability and coronary anatomy amenable to surgical grafting. Surgical

revascularization is also indicated in the setting of mechanical complications of MI, such as ventricular

septal defect, free wall rupture, or acute mitral regurgitation. 1 Restoration of coronary blood flow with

emergency CABG can limit myocardial injury and cell death if performed within 2 or 3 hours of symptom

onset. Emergency CABG carries a higher risk of perioperative morbidity (bleeding and MI extension) and

mortality than elective CABG. The risk of operative mortality during emergency CABG is increased in

patients who are in cardiogenic shock, those with previous CABG surgery, and those with multivessel

disease. On the other hand, urgent CABG confers a survival benefit for patients with recurrent ischemia
post-MI whose coronary anatomy is unsuitable for complete revascularization with PCI. Elective CABG

improves survival in post-MI patients who have left main artery disease, three-vessel disease, or two-

vessel disease not amenable to PCI. The timing of elective CABG post-MI is controversial, but

retrospective studies have indicated that when CABG is performed as early as 3 to 7 days post-MI,

operative mortality is equivalent to CABG performed on non-MI patients. 1

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers

Drugs of the angiotensin-converting enzyme inhibitors (ACEI) class have been shown to decrease

mortality rates for patients with both STEMI and NSTEMI who have impaired left ventricular ejection

fraction (lower than 40%). Benefit has also been shown for diabetic patients with left ventricular

dysfunction. In such patients, an ACEI or angiotensin receptor blocker (ARB) should be administered

within 24 hours of admission and continued indefinitely. 6

Oral ACEI therapy is recommended for MI patients within the first 24 hours of symptom onset, if no

contraindications exist. 1Contraindications to ACEI use include hypotension and declining renal function.

The use of an ACEI 4 to 6 weeks after presentation of an MI is recommended for patients with congestive

heart failure, left ventricular dysfunction (ejection fraction less than 40%), hypertension, or diabetes.

ACEIs decrease myocardial afterload through vasodilation. One effective strategy for instituting an ACEI is

to start with a low-dose, short-acting agent and titrate the dose upward toward a stable target

maintenance dose at 24 to 48 hours after symptom onset. Once a stable maintenance dose has been

achieved, the short-acting agent can be continued or converted to an equivalent-dose long-acting agent to

simplify dosing and encourage patient compliance ( Table 8 ). For patients intolerant of ACEIs, blockade

with angiotensin receptor blocker (ARB) therapy may be considered. The use of ARBs post-STEMI remains

somewhat controversial, although valsartan monotherapy (target dose, 160 mg twice daily) is

recommended for STEMI patients intolerant of ACEIs who have evidence of left ventricular dysfunction. 6
Table 8: Angiotension-Converting Enzyme Inhibitors

Agent Divided Doses Dosage

Captopril Three times daily 12.5-450 mg/day

Enalapril Twice daily 2.5-40 mg/day

Moexipril Once or twice daily 7.5-30 mg/day

Benazepril Once or twice daily 5-40 mg/day

Quinapril Once or twice daily 5-80 mg/day

Ramipril Once or twice daily 2.5-20 mg/day

Perindopril Once or twice daily 4-16 mg/day

Trandolapril Once daily 1-4 mg/day

Fosinopril Once daily 10-40 mg/day

Lisinopril Once daily 2.5-40 mg/day

© 2002 The Cleveland Clinic Foundation.

Smoking Cessation

As noted earlier (“Risk Factors”), smoking is a major risk factor for coronary artery disease and MI. For

patients who have undergone an MI, smoking cessation is essential to recovery, long-term health, and

prevention of reinfarction. All STEMI and NSTEMI patients with a history of smoking should be advised to

quit and offered smoking cessation resources, including nicotine replacement therapy, pharmacologic

therapy (bupropion), and referral to behavioral counseling or support groups. 6 Smoking cessation

counseling should begin in the hospital, at discharge, and during follow-up. The American Lung Association

maintains a website ( with updates on public health initiatives to reduce tobacco

use; it is a resource for smoking cessation strategies for patients and health care providers. Other public

and private sources of smoking cessation information available on line include the following:


An individual patient's long-term outcome following a MI is dependent on numerous variables, some of

which are not modifiable from a clinical standpoint. However, patients can modify other variables by

complying with prescribed therapy, adopting lifestyle changes, or both.

Cardiac Stress Testing

Cardiac stress testing post-MI has established value in risk stratification and assessment of functional

capacity. 1 The timing of performing cardiac stress testing remains debatable. The degree of allowable

physiologic stress during testing is dependent on the length of time from MI presentation. Stress testing is

not recommended within several days post-MI. Only submaximal stress tests should be performed in

stable patients 4 to 7 days after an MI. Symptom-limited stress tests are recommended 14 to 21 days

after an MI. Imaging modalities can be added to stress testing in patients whose electrocardiographic

response to exercise is inadequate to assess for ischemia confidently (e.g., complete left bundle branch

block, paced rhythm, accessory atrioventricular pathway, left ventricular hypertrophy, digitalis use, and

resting ST-segment abnormalities). 1

From a prognostic standpoint, an inability to exercise and exercise-induced ST-segment depression are

associated with higher cardiac morbidity and mortality compared with patients able to exercise and

without ST-segment depression. 1Exercise testing identifies patients with residual ischemia for additional
efforts at revascularization. Exercise testing also provides prognostic information and acts as a guide for

post-MI exercise prescription and cardiac rehabilitation. 1

Lipid Management

All post-MI patients should be on an American Heart Association step II diet (less than 200 mg

cholesterol/day, less than 7% of total calories from saturated fats). Post-MI patients with LDL cholesterol

levels higher than 100 mg/dL on a step II diet are recommended to be on drug therapy to lower LDL

cholesterol levels to less than 100 mg/dL. Post-MI patients with high-density lipoprotein (HDL) cholesterol

levels lower than 35 mg/dL on a step II diet are recommended to participate in a regular exercise program

and on drug therapy designed to increase HDL cholesterol levels. 1 Recent data have indicated that all MI

patients should be on statin therapy, regardless of lipid levels or diet.

Long-term Medications

Most oral medications instituted in the hospital at the time of MI will be continued long term. Therapy with

aspirin and beta blockade is continued indefinitely in all patients. ACEIs are continued indefinitely in

patients with congestive heart failure, left ventricular dysfunction (ejection fraction less than 0.40),

hypertension, or diabetes. 1 A lipid-lowering agent, specifically a statin, in addition to dietary modification,

is continued indefinitely.

Implantable Cardiac Defibrillators

The results of a multicenter automatic defibrillator implantation trial have expanded the indications for

automatic implantable cardioverter-defibrillators (AICDs) in patients post-MI. The trial demonstrated a

31% relative risk reduction in all-cause mortality with the prophylactic use of an AICD in patients post-MI

with ejection fractions of less than 30%. 4 This trial, which broadens the indications for AICD, will have to

address the high costs of device therapy.

Cardiac Rehabilitation

Cardiac rehabilitation provides a venue for continued education, reinforcement of lifestyle modification,

and adherence to a comprehensive prescription of therapies for recovery from MI, which includes exercise

training. Participation in cardiac rehabilitation programs post-MI is associated with decreases in

subsequent cardiac morbidity and mortality. 1 Other benefits include improvements in quality of life,

functional capacity, and social support. However, only a minority of post-MI patients actually participate in

formal cardiac rehabilitation programs because of several factors, including lack of structured programs,

physician referrals, low patient motivation, noncompliance, and financial constraints. 1


• MI results from myocardial ischemia and cell death, most often because of an intra-arterial

thrombus superimposed on an ulcerated or unstable atherosclerotic plaque.

• MI affects 800,000 in the United States annually; approximately 250,000 die before reaching the


• MI risk factors include high blood cholesterol level, diabetes mellitus, hypertension, and tobacco

use. Males are more likely to suffer an MI.

• Diagnosis is based on the clinical history, ECG, and blood test results, especially creatinine

phosphokinase (CK), CK MB fraction, and troponin I and T levels.

• Outcome following an MI is determined by the infarct size and location, and by timely medical


• Aspirin, nitrates, and beta blockers are critically important early in the course of MI for all

patients. For those with ST-elevation myocardial infarction, and for those with new left bundle

branch block, coronary angiography with angioplasty and stenting should be undertaken within

90 minutes of arrival at facilities with expertise in these procedures. Fibrinolytic therapy should

be used in situations in which early angiographic intervention is not possible.

• Postdischarge management requires ongoing pharmacotherapy and lifestyle modification.

3.) Newborn Screening

Newborn screening, often referred to as the “PKU test,” is a simple, inexpensive blood test
performed on babies in the first 48 hours after birth to look for serious and often life-threatening
disorders. At least 4 million babies in the United States are tested every year, and severe disorders
are detected in about 3,000. Most state-required screening is free or costs a nominal fee.

Standard newborn screening consists of a small sample of blood being taken from your baby before
being discharged from the hospital. The heel used to be the most common place to take the sample,
so it is often called a “heel stick,” but the blood may also be drawn from the inside of the elbow.
The blood should be taken around 48 hours after birth. Some tests, such as the one for PKU, may
not give accurate results if it is performed too early. Because many babies are discharged early
from the hospital, some babies are tested within the first 24 hours and then must be retested 1 to 2
weeks later. The blood is placed on a piece of filter paper, allowed to dry for 4 to 6 hours, and is
then sent to a laboratory for analysis. The results of the screening usually take a few weeks to come
back. Many labs will call the physician in the case of abnormal results, while normal results will be
sent in the mail.

Newborn screening tests for disorders that can cause mental retardation, severe illness, and
premature death if not detected at birth. For example, hypothyroidism is the most common disorder
identified by routine screening, affecting 1 baby in 3,000. Congenital hypothyroidism is a thyroid
hormone deficiency that retards growth and brain development; but if it is detected in time, the
baby can be treated with oral doses of thyroid hormone to permit normal development.

If your baby’s test results come back as abnormal, try not to be overly alarmed; the initial
screening tests give only preliminary information that must be followed up by more precise testing.
False-positive results are possible with newborn screening and most babies turn out to be normal
after further testing.

There is currently no federal standard for which disorders newborns are tested, and as a result,
screening varies widely from state to state. However, all states screen for at least two disorders:
phenylketonuria (PKU) and hypothyroidism, and many states include sickle cell anemia,
galactosemia, and homocystinuria.

Expanded newborn screening (ENBS) is available through private companies and laboratories for an
additional charge and uses Tandem Mass Spectrometry (MS/MS) to test for up to 40 rare disorders.
ENBS is expensive and most states don’t have the highly-trained experts required to run the very
specialized screenings and then effectively and accurately interpret the results; therefore, it is not
available in all areas. In addition, there are no cures or known treatments for many of the disorders
for which ENBS screens.
Newborn screening is the process of testing newborn babies for
treatable genetic, endocrinologic, metabolic and hematologic diseases.[1][2] Robert Guthrie is given much of
the credit for pioneering the earliest screening for phenylketonuria in the late 1960s using blood samples
on filter paper obtained by pricking a newborn baby's heel on the second day of life to get a few drops of
blood. [3] Congenital hypothyroidism was the second disease widely added in the 1970s.[4] The
development of tandem mass spectrometry screening by Edwin Naylor and others in the early 1990s led
to a large expansion of potentially detectable congenital metabolic diseases that affect blood levels of
organic acids.[5] Additional tests have been added to many screening programs over the last two decades.
Newborn screening has been adopted by most countries around the world, though the lists of screened
diseases vary widely.

Disease qualification

Common considerations in determining whether to screen for disorders:

1. A disease that can be missed clinically at birth

2. A high enough frequency in the population

3. A delay in diagnosis will induce irreversible damages to the baby

4. A simple and reasonably reliable test exists

5. A treatment or intervention that makes a difference if the disease is detected early

Newborn Screening Program in the Philippines

The following tests are mandated in the R.A. 9288 or Newborn Screening program of 2004.Newborn

screening is available in practicing health institutions (hospitals, lying-ins, Rural Health Units and Health

Centers) with cooperation with DOH. If babies are delivered at home, babies may be brought to the

nearest institution offering newborn screening. A negative screen mean that the result of the test is

normal and the baby is not suffering from any of the disorders being screened. In case of a positive

screen, the NBS nurse coordinator will immediately inform the coordinator of the institution where the
sample was collected for recall of patients for confirmatory testing. Babies with positive results should be

referred at once to the nearest hospital or specialist for confirmatory test and further management.

Should there be no specialist in the area, the NBS secretariat office will assist its attending physician.

Disorders Screened:

Heel Prick Method for the newborn screening

 CH (Congenital hypothyroidism) - is a condition of thyroid hormone deficiency present at birth.

Approximately 1 in 4000 newborn infants has a severe deficiency of thyroid function, while even more

have mild or partial degrees. If untreated for several months after birth, severe congenital

hypothyroidism can lead to growth failure and permanent mental retardation. Treatment consists of a

daily dose of thyroid hormone (thyroxine) by mouth. Because the treatment is simple, effective, and

inexpensive, nearly all of the developed world practices newborn screening to detect and treat

congenital hypothyroidism in the first weeks of life.

 CAH (Congenital adrenal hyperplasia) - refers to any of several autosomal recessive diseases

resulting from mutations of genes for enzymes mediating the biochemical steps of production of

cortisol from cholesterol by the adrenal glands (steroidogenesis). Most of these conditions involve

excessive or deficient production of sex steroids and can alter development of primary or secondary

sex characteristics in some affected infants, children, or adults. Approximately 95% of cases of CAH

are due to 21-hydroxylase deficiency.

 GAL (Galactosemia) - is a rare genetic metabolic disorder which affects an individual's ability to

properly metabolize the sugar galactose. Lactose in food (such as dairy products) is broken down by

the body into glucose and galactose. In individuals with galactosemia, the enzymes needed for further

metabolism of galactose are severely diminished or missing entirely, leading to toxic levels of

galactose to build up in the blood, resulting in hepatomegaly (an enlarged liver), cirrhosis, renal

failure, cataracts, and brain damage. Without treatment, mortality in infants with galactosemia is

about 75%.

 PKU (Phenylketonuria) - is an autosomal recessive genetic disorder characterized by a deficiency

in the enzyme phenylalanine hydroxylase (PAH). This enzyme is necessary to metabolize the amino

acid phenylalanine to the amino acid tyrosine. When PAH is deficient, phenylalanine accumulates and
is converted into phenylpyruvate (also known as phenylketone), which is detected in the urine. PAH is

found on chromosome number 12.Left untreated, this condition can cause problems with brain

development, leading to progressive mental retardation and seizures. However, PKU is one of the few

genetic diseases that can be controlled by diet. A diet low in phenylalanine and high in tyrosine can be

a very effective treatment. There is no cure. Damage done is irreversible so early detection is crucial.

 G6PD Deficiency - is an X-linked recessive hereditary disease characterized by abnormally low

levels of the glucose-6-phosphate dehydrogenase enzyme (abbreviated G6PD or G6PDH). It is a

metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell


 Newborn screening results are available within three weeks after the NBS Lab receives and tests

the samples sent by the institutions. Results are released by NBS Lab to the institutions and are

released to your attending birth attendants or physicians.Parents may seek the results from the

institutions where samples are collected. Christian Nieto,EACSN

Newborn screening in the United States

The following tests are mandated (required to be performed on every newborn born in the state) in most

of the United States. According to the U.S. Centers for Disease Control, approximately 3,000 babies with

severe disorders are identified in the United States each year using newborn screening programs at

current testing rates. States vary, and not all tests are required in every state, and a few states mandate

more than this. The first test to be universally mandated across the U.S. was the Guthrie test for

phenylketonuria (PKU), and in many areas and hospitals, the newborn blood test is often erroneously

referred to as a "PKU test", even though all states now universally test for

congenital hypothyroidism, galactosemia, and increasing numbers of other diseases as well.

 Endocrine disorders: Congenital adrenal hyperplasia (CAH), Congenital hypothyroidism

 Blood cell disorders: sickle-cell disease (SS)

 Inborn errors of carbohydrate metabolism: Galactosemia

 Inborn errors of amino acid metabolism: Phenylketonuria (PKU), Maple syrup urine

disease (MSUD), Homocystinuria

 Inborn errors of organic acid metabolism: Biotinidase deficiency

For a recent state-by-state list, see U.S. National Newborn Screening and Genetics Resource Center.

According to this resource, the only tests mandated in every state are the following:

 CH - Congenital hypothyroidism

 H-HPE - Benign hyperphenylalaninemia

 PKU -- Phenylketonuria/hyperphenylalaninemia

 HEAR - Hearing

 GALT - Transferase deficient galactosemia

Usual procedures and responses to positive results

Heel blood on a filter paper card for the newborn screening

In nearly all of the United States, the newborn screening program is a division of the state health

department. State law mandates collecting a sample by pricking the heel of a newborn baby to get

enough blood (typically, two to three drops) to fill a few circles on filter paper labeled with names of

infant, parent, hospital, and primary physician. It is usually specified that the sample be obtained on the

second or third day of life, after protein-containing feedings (i.e., breast milk or formula) have started,

and the postnatal TSH surge subsided. Every hospital in the state as well as

independent midwives supervising home deliveries are required to collect the papers and mail each batch

each day to the central laboratory.

The state health department agency in charge of screening will either run a laboratory or contract with a

laboratory to run the mandated screening tests on the filter paper samples. The goal is to report the

results within a short period of time. If screens are normal, a paper report is sent to the submitting

hospital and parents rarely hear about it.

If an abnormality occurs, employees of the agency, usually nurses, begin to try to reach the physician,

hospital, and/or nursery by telephone. They are persistent until they can arrange an evaluation of the

infant by an appropriate specialist physician (depending on the disease). The specialist will attempt to

confirm the diagnosis by repeating the tests by a different method or laboratory, or by performing other

corroboratory tests. Depending on the likelihood of the diagnosis and the risk of delay, the specialist will

initiate treatment and provide information to the family. Performance of the program is reviewed regularly

and strenuous efforts are made to maintain a system that catches every infant with these diagnoses.

Guidelines for newborn screening and follow up have been published by the American Academy of


Expanded screening and controversies

With the development of tandem mass spectrometry in the early 1990s, the number of detectable

diseases quickly grew, especially in the categories of fatty acid oxidation disorders and organic acidoses.

Screening tests for the disorders listed below (and an increasing number of others) are now available,

though not universally mandated. There is considerable variability from state to state, and sometimes

from hospital to hospital within a state, on disease that are screened. To make matters more confusing,

some hospitals routinely obtain supplemental screening (most of the tests below) on all infants even if not

mandated by the state or requested by parents. In recent years in the United States, expanded newborn

screening with tandem mass spectrometry has become a profitable commercial venture.

Newborn screening tests have become a subject of political controversy in the last decade. Two California

babies, Zachary Wyvill and Zachary Black, were both born with Glutaric acidemia type I. Wyvill's birth

hospital only tested for the four diseases mandated by state law, while Black was born at a hospital that

was participating in an expanded testing pilot program. Black's disease was treated with diet and

vitamins; Wyvill's disease went undetected for over six months, and during that time the damage from the

enzyme deficiency became irreversible. Birth-defects lobbyists pushing for broader and more universal

standards for newborn testing cite this as an example of how much of an impact testing can have.

Instituting MS/MS screening often requires a sizable up front expenditure. When states choose to run their

own programs the initial costs for equipment, training and new staff can be significant. To avoid at least a

portion of the up front costs, some states such as Mississippi have chosen to contract with private labs for

expanded screening. Others have chosen to form Regional Partnerships sharing both costs and resources.

But for many states, screening is an integrated part of the department of health which can not or will not

be easily replaced. Thus the initial expenditures can be difficult for states with tight budgets to justify.

Screening fees have also increased in recent years as healthcare costs rise and more states add MS/MS

screening to their programs. (See Report of Summation of Fees Charged for Newborn Screening, 2001–

2005) Dollars spent for these programs may reduce resources available to other potentially lifesaving

programs. It has been recommended that one disorder, Short Chain Acyl-coenzyme A Dehydrogenase

Deficiency, or SCAD, be eliminated from screening programs, due to a "spurious association between

SCAD and symptoms. [7]

However, recent studies suggest that expanded screening is cost effective

(see ACMG report page 94-95 and articles published in Pediatrics ' . Advocates are quick to point out
[8] [9]

studies such as these when trying to convince state legislatures to mandate expanded screening.

Expanded newborn screening is also opposed by among some health care providers who are concerned

that effective follow-up and treatment may not be available, that false positive screening tests may cause

harm, and issues of informed consent[10].

Conditions and disorders

The following list includes most of the disorders detected by the expanded or supplemental newborn

screening by mass spectrometry. This expanded screening is not yet universally mandated by most states,

but may be privated purchased by parents or hospitals at a cost of approximately US$80. Perhaps one in

5,000 infants will be positive for one of the metabolic tests below (excluding the congenital infections).

The 29 marked with a "@" were recommended as "core panel" by the 2005 report of the American College

of Medical Genetics (ACMG). The incidences reported below are from their report, pages 143-307, though

the rates may vary in different populations. (WARNING: The file is a very large PDF.)

Blood cell disorders

 Glucose-6-phosphate dehydrogenase deficiency (G6PD)

 Sickle cell anemia (Hb SS) > 1 in 5,000; among African-Americans 1 in 400

 Sickle-cell disease (Hb S/C) > 1 in 25,000

 Hb S/Beta-Thalassemia (Hb S/Th) > 1 in 50,000

Inborn errors of amino acid metabolism

 Tyrosinemia I (TYR I) < 1 in 100,000

 Tyrosinemia II

 Argininemia

 Argininosuccinic aciduria (ASA) < 1 in 100,000

 Citrullinemia (CIT) < 1 in 100,000

 Phenylketonuria (PKU) > 1 in 25,000

 Maple syrup urine disease (MSUD) < 1 in 100,000

 Homocystinuria (HCY) < 1 in 100,000

Inborn errors of organic acid metabolism

 Glutaric acidemia type I (GA I) > 1 in 75,000

 Glutaric acidemia type II

 HHH syndrome (Hyperammonemia, hyperornithinemia, homocitrullinuria syndrome)

 Hydroxymethylglutaryl lyase deficiency (HMG) < 1 in 100,000

 Isovaleric acidemia (IVA) < 1 in 100,000

 Isobutyryl-CoA dehydrogenase deficiency

 2-Methylbutyryl-CoA dehydrogenase deficiency

 3-Methylcrotonyl-CoA carboxylase deficiency (3MCC) > 1 in 75,000

 Beta-methyl crotonyl carboxylase deficiency

 3-Methylglutaconyl-CoA hydratase deficiency

 Methylmalonyl-CoA mutase deficiency (MUT) > 1 in 75,000

 Methylmalonic aciduria, cblA and cblB forms (MMA, Cbl A,B) < 1 in 100,000

 Beta-ketothiolase deficiency (BKT) < 1 in 100,000

 Propionic acidemia (PROP) > 1 in 75,000

 Adenosylcobalamin synthesis defects

 Multiple-CoA carboxylase deficiency (MCD) < 1 in 100,000

Inborn errors of fatty acid metabolism

 Carnitine palmityl transferase deficiency type 2 (CPT)

 Long-chain acyl-CoA dehydrogenase deficiency (LCAD)

 Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) > 1 in 75,000

 Short-chain acyl-CoA dehydrogenase deficiency (SCAD)

 Short-chain hydroxy Acyl-CoA dehydrogenase deficiency (SCHAD)

 Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) > 1 in 25,000

 Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD) > 1 in 75,000

 Carnitine/acylcarnitine Translocase Deficiency (Translocase)

 Multiple acyl-CoA dehydrogenase deficiency (MADD)

 Trifunctional protein deficiency (TFP) < 1 in 100,000

 Carnitine uptake defect (CUD) < 1 in 100,000

Congenital infections

 Congenital toxoplasmosis


Miscellaneous multisystem diseases

 Cystic fibrosis (CF) > 1 in 5,000

 Maternal vitamin B12 deficiency

 Congenital hypothyroidism (CH) > 1 in 5,000

 Biotinidase deficiency (BIOT) > 1 in 75,000

 Congenital adrenal hyperplasia (CAH) > 1 in 25,000

 Classical galactosemia (GALT) > 1 in 50,000

Newborn screening by other methods than blood testing

 Congenital deafness (HEAR) > 1 in 5,000

Newborn screening programs worldwide

Newborn screening has also been adopted by most countries in Europe and around the world, though the

lists of screened diseases vary widely.