Hyperkalemia (Hyper- High; Kalium, Potassium; -Emia, "in the Blood") Is
Transcript of Hyperkalemia (Hyper- High; Kalium, Potassium; -Emia, "in the Blood") Is
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.
Diagnosis
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 failure.
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.
[edit]Pseudohyperkalemia
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]
Pathophysiology
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]
[7] 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]
Treatment
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.
Prevention:
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
Prevalence
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
strategies.
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.
Hypertension.
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).
Pathophysiology
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.
Diagnosis
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.
Electrocardiography
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
Echocardiography
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.
Treatment
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)
Intervention TimingAcute MI
STEMI
Acute MI
NSTEMIComments
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
angiography,
angioplasty
Within 90 min after
arrival
Also for LBBB (in
facilities so equipped)
Reperfusion Within 12 hr of onset
of symptoms
LDL cholesterol
assessment
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
counseling
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 TreatmentAspirin
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.
Nitrates
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
HeparinUnfractionated 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
heparin
60-70 U/kg IV load (max, 5000 U); 12-15 U/kg/hr IV maintenance drip;
nomogram—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.Fibrinolytics
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
Agent DosagePatency at 90
minutes
Alteplase
(Activase)
Body weight > 67 kg: 15-mg loading dose + 50 mg/30 min +
35 mg/60 min IV
75%
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
(Retavase)
10 U over 2 min; wait 30 min; 10 U/2 min IV 75%
Streptokinase
(Streptase)
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 hr
Eptifibatid
e
Acute coronary syndrome;
coronary intervention
180 mcg/kg IV loading dose; 2.0 mcg/kg/min IV
maintenance; duration of infusion, up to 72 hr
Tirofiban Acute coronary syndrome;
coronary intervention
0.4 mcg/kg/min x 30 min IV loading dose; 0.1 mcg/kg/min
IV maintenance; duration of infusion, 12-24 hr
© 2002 The Cleveland Clinic Foundation.Other Treatment OptionsPercutaneous 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 (http://www.lungusa.org) 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:
Outcomes
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
Summary
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
hospital.
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
intervention.
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
metabolism.
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
Pediatrics.[6]
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 [8]'[9]. Advocates are quick to point out 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
HIV
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.