Assessing risk to QT interval

Paul J Setlak, John D Kanell. Drug Topics. Oradell: Apr 16, 2007. Vol. 151, Iss. 8; pg.
H8, 1 pgs
Abstract (Summary)
Two pharmacists shared their views on treating pneumonia with QT prolongation. Paul J.
Setlak, Pharmacy Practice Resident and Clinical Associate, University of Illinois at
Chicago, College of Pharmacy, said QT prolongation potential associated with
fluoroquinolones differs among individual agents: Sparfloxacin and grepafloxacin show
the greatest incidence; other agents, e.g., moxifloxacin and levofloxacin, show lesser
incidence. Her recommendation would be amoxicillin/clavulanate extended-release 2,000
mg every 12 hours (renally adjusted) and azithromycin 500 mg IV for two days, followed
by 500 mg orally for seven days. John D. Kanell, Coordinator of Drug Information
Services, Pharmacy Wilson N. Jones Medical Center, said independent risk factors for
QTc prolongation include female gender, age 65 years or older, bradycardia,
hypokalemia, a history of cardiac disease, and concomitant QT-prolonging drugs.
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Copyright Advanstar Communications, Inc. Apr 16, 2007

A 70-year-old woman, T.R., has been transferred from an extended care nursing facility
to your hospital with symptoms of fever, dyspnea with respiratory difficulty, cough, and
sputum production. Her current medications include methadone 200 mg/ day (pain
syndrome), risperidone (Risperdal, fanssen) 2 mg twice daily, digoxin 0.125 mg daily,
and furosemide 20 mg twice daily. T.R.'s chest X-ray shows a pulmonary infiltrate in the
right middle and upper lobes of the right lung with lobar consolidation. She is diagnosed
with pneumonia, and her physician prescribes moxifloxacin (Avclox, Bayer) 400 mg
IV/24 hours. Your student calls this order to your attention; her journal club recently
discussed the problem of QT prolongation and this regimen concerns her. What do you
recommend?
The medications T.R. is already taking may indicate a significant underlying
dysrhythmia. She is receiving a high dose of methadone, which according to the
literature, can contribute to QT prolongation and torsades de pointes. She is taking
digoxin and furosemide without potassium supplementation (T.R. could be hypokalemic),
and she is elderly. Studies show individuals with underlying cardiac anomalies, advanced
age, female sex, concurrent QT-prolonging agents, hypokalemia, or hypomagnesemia
have an increased incidence of QT prolongation and torsades de pointes. These factors
should be considered in antibiotic choice.
According to recent pneumonia guidelines, individuals presenting from long-term care
facilities with pneumonia should receive a respiratory fluoroquinolone (levofloxacin,
moxifloxacin) as inpatients. The QT prolongation potential associated with
fluoroquinolones differs among individual agents: Sparfloxacin (Zagam, Mylan) and
grepafloxacin (Raxar, Otsuka) show the greatest incidence; other agents, e.g.,
moxifloxacin and levofloxacin (Levoquin, Ortho-McNeil), show lesser incidence. These
conclusions are drawn from multiple trials of more than 200 patients and adverse
reporting through the FDA. We do not know how well T.R. is rate/rhythm controlled, so
to err on the side of caution, it is best to proceed with the secondary guideline
recommendation, a beta-lactam and an advanced macrolide.
My recommendation would be amoxicillin/clavulanate extended-release 2,000 mg every
12 hours (renally adjusted) and azithromycin 500 mg IV for two days, followed by 500
mg orally for seven days. This was based on the possibility that moxifloxacin and
methadone may additively contribute to QT prolongation and possible torsades, as well
as the patient's other risk factors for QT prolongation. If the prescriber insists on
moxifloxacin, monitoring parameters should include blood pressure, heart rate,
electrocardiogram (EKG), potassium, liver panel, repeat chest X-ray, with antibiotic
discontinuation if QTc is greater than 440 milliseconds.
Paul J. Setlak, Pharm.D.
Pharmacy Practice Resident and Clinical Associate
University of Illinois at Chicago
College of Pharmacy
Independent risk factors for QTc prolongation include female gender, age 65 years or
older, bradycardia, hypokalemia, a history of cardiac disease, and concomitant QT-
prolonging drugs. TR. presents with several of these risk factors in addition to the
potential individual and/or synergistic effects of moxifloxacin, methadone, and
risperidone. Fluoroquinolones have been associated with cardiac arrhythmias in trials and
case reports. In fact, severe cardiac arrhythmias related to sparfloxacin and grepafloxacin
led to these drugs being withdrawn from the market.
In a prospective, randomized, double-blind trial of 387 patients reviewing cardiac safety
of moxifloxacin and levofloxacin, investigators found comparable cardiac rhythm safety
profiles in high-risk elderly patients with community-acquired pneumonia (CAP). Mean
QTc change for moxifloxacin after three days of treatment was determined to be +6.4 ms
(+/- 23 ms). While the clinical significance of a single agent affecting cardiac rhythm
may not require intervention, the combination of several risk factors may warrant
additional investigation. T.R. should have a baseline EKG, electrolytes, and her cardiac
history assessed before initiating a quinolone antibiotic. A sputum culture obtained prior
to antibiotic therapy may be beneficial in isolating the causative pathogen and narrowing
the antibiotic spectrum. Infectious Diseases Society of America guidelines for CAP
would support use of ceftriaxone and azithromycin as a reasonable alternative to a
fluoroquinolone alone. Since T.R. lives in an extended care nursing facility, multidrug
resistance may also be a factor in empiric antimicrobial selection.
John D. Kartell, Pharm.D., BCPS
Coordinator of Drug Information Services, Pharmacy
Wilson N. Jones Medical Center
Sherman, Texas
305 PQ REVERSE_CHRON 1284714615

Indexing (document details)

Subjects: Risk factors, Heart rate, Pneumonia, Medical treatment, Antibiotics
Classification 9190 United States, 8320 Health care industry
Codes
Locations: United States--US
Author(s): Paul J Setlak, John D Kanell
Document Commentary
types:
Section: CLINICAL TWISTERS
Publication Drug Topics. Oradell: Apr 16, 2007. Vol. 151, Iss. 8; pg. H8, 1 pgs
title:
Source type: Periodical
ISSN: 00126616
ProQuest 1268710011
document ID:
Text Word 674
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=PQD

Hypokalemic periodic paralysis: A case study

Kelley McKeta Anderson. American Journal of Critical Care. Aliso Viejo: May 1998.
Vol. 7, Iss. 3; pg. 236, 4 pgs
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Full Text
(2021 words)
Copyright American Association of Critical - Care Nurses May 1998

Hypokalemic periodic paralysis (HPP) is a rare disorder characterized by intermittent

muscle weakness that varies in frequency, duration. and severity.1 Extracellular
hypokalemia is the primary biochemical abnormality during an attack2; however, total
body potassium stores remain normal.3 The clinical features are specific, and the
diagnosis can be made on the basis of these features. Unfortunately, even when common
complications of hypokalemia are apparent, HPP is often not diagnosed, because
healthcare providers are not familiar with the disorder.2
Case Report
A 27-year-old man came to the emergency department because he had tingling all over
his body and numbness in his fingers and toes. The day before, he had exhibited signs
and symptoms consistent with a diagnosis of an allergic reaction to poison ivy and had
been prescribed hydroxyzine (Vistaril) and methylprednisolone.
The patient was anxious but was appropriately alert and oriented. Cranial nerves II to XII
were grossly intact. Deep tendon reflexes were 1/4 throughout. The patient had gross
motor deficits and could not bring his torso off the stretcher. He had gravity resistance in
the hands and less than gravity resistance at the biceps, deltoids, and lower extremities.
He had no sensory deficits; responses to pinprick, light touch, and vibration were normal.
Vital signs were blood pressure, 150/81 mm Hg; heart rate, 106 beats per minute;
respirations, 16 breaths per minute; and body temperature, 36.8 deg C. The patient's
medical history included no surgical procedures and no major medical problems. He
acknowledged that he was currently under stress because of a recent loss of employment.
The day before admission, he had engaged in heavy physical work outside. The diagnosis
was hyperventilation and motor weakness of undetermined etiology, and the patient was
admitted to the hospital. The healthcare team speculated a wide variety of causes for the
generalized weakness, including central nervous system changes, neuromuscular junction
disorders, acute myopathies, polyneuropathies, psychogenic causes, and electrolyte
abnormalities.4 Laboratory tests and 12-lead ECG were done. Arterial blood gas values
were pH, 7.504; partial pressure of carbon dioxide, 24 mm Hg; partial pressure of
oxygen, 108 mm Hg; and bicarbonate, 19.4 mmol/L. Results of thyroid function tests
revealed primary hyperthyroidism: T^sub 4^, 179 nmol/L (normal, 64-154 nmol/L);
T^sub 3^ uptake, 0.44 (normal, 0.25-0.40); and thyroid-stimulating hormone, 0.0 mU/L
(normal, 0.42-5.47 mU/L). The 12lead ECG findings were consistent with hypokalemia
and showed U waves, ST-segment depression, and prolonged QT intervals (Figure 1).
The cardiac rhythm was sinus tachycardia. The most impressive finding was a potassium
level of 1.7 mmol/L (normal, 3.6-5.0 mmol/L). Otherwise the chemistry profile was
unremarkable.
The cause of the patient's weakness was apparent; the diagnosis was HPP. The patient
immediately received 40 mmol of oral potassium and an IV infusion of 60 mmol of
potassium in 250 mL of normal saline at a rate of 15 mmol/h. Correction of the
hypokalemia quickly reversed the muscular weakness. After 30 minutes, the patient
began to regain gross motor movement in the upper extremities. The serum potassium
level increased incrementally-- from 1.7 mmol/L at 10:55 AM, to 2.1 mmol/L at 2:24
PM, to 5.9 mmol/L at 9:08 PM, to 5.1 mmol/L at 3:10 AM-and within the next several
hours, the patient regained fine motor function. The following day, he had strong motor
function and improved ECG findings (Figure 2). One year later HPP had not recurred.
Pathophysiology
HPP occurs in 2 major forms, a familial (primary) form and an acquired (secondary)
thyrotoxic form, with identical clinical and biochemical features. Both forms lead to an
abnormality in the membrane sodium channels. An intracellular influx of potassium
occurs, and cells lose the ability to sustain an action potential. The resting membrane
potential is so low that the sodium channel becomes inactivated. The channel itself
becomes abnormally sensitive to inactivation by even a minor depolarization of the
membrane.
The familial form of HPP is acquired through an autosomal dominant inheritance pattern.
This form is more common in whites than in other racial groups,2 and patients have
normal thyroid function. The onset is usually during the first to second decades of life. In
the familial form of HPP, paralytic attacks affect 60% of patients.' After the age of 40
years, the attacks occur less often, and the main sign is permanent muscle weakness.5
Permanent muscle weakness at an older age is a common feature in almost all patients
with the inherited form of HPP, and by the sixth or seventh decade of life, the patients
can no longer walk.1
The second major form of HPP is caused by thyrotoxicosis, which is associated with a
number of muscular disorders.6 The thyroid hormones increase sodium-potassium
adenosinetriphosphatase (ATPase) activity in the skeletal muscle, thereby decreasing
extracellular levels of potassium. Increased levels of thyroid hormone augment tissue
response to beta-adrenergic stimulation, and this augmentation increases ATPase
activity.2 HPP associated with hyperthyroidism has a sporadic distribution and an
undetermined inheritance pattern.2 Patients with thyrotoxic HPP have attacks only when
they have hyperthyroidism.2 The onset of this form of HPP is in adult life, a time that
coincides with the onset of hyperthyroidism.
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Figure 1.

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Figure 2

Thyrotoxic HPP is rare in whites and African-- Americans and more common in Asians.7
In Japan, hypokalemic paralysis occurs in 1.9% of cases of hyperthyroidism.2 In the
United States, hyperthyroidism is often subclinical for months to years, and
hyperthyroidism is not always apparent in patients with thyrotoxic HPP.2 The usual
clinical manifestations of hyperthyroidism (sweating, heat intolerance, and
exophthalmos) are absent in 13% of patients with thyrotoxic HPP.
The clinical features of both forms of HPP are similar and are primarily attributable to
extracellular hypokalemia. Patients usually have some prodromal symptoms, including
muscle aches and cramps. Generalized attacks begin proximally and spread distally.
Patients often awaken early in the morning with widespread paralysis. The diurnal pattern
is attributed to rest, which is associated with a net influx of potassium into the muscles.
Weakness in the lower extremities precedes weakness in the upper extremities. Limb
involvement is generally symmetric, with a combination of one or more extremities
affected.6 HPP is characterized by the absence of sensory disturbances (pain, diplopia,
ptosis1) and any involvement of mental functions.2
Signs and symptoms have a profound effect on patients' activities of daily living. Without
interventions, the paralytic attacks last 7 to 14 days. Recovery of muscle function is in
reverse order of the onset of paralysis.2 Attacks can be precipitated by emotional stress,
exercise, carbohydrate-rich meals, cold, menses, pregnancy, alcohol consumption, and
rest after heavy physical work.3,8 The precipitating event usually occurs 2 to 12 hours
before the attack,1 and attacks are more common during hot-weather months than during
other months. The seasonal variability may be related to an increased loss of potassium
through perspiration and the ingestion of drinks with large amounts of sugar.
Another interesting feature of HPP is the predominance of the disorder, both the familial
and the thyrotoxic forms, in men. Although thyrotoxicosis is more prevalent in women
than in men, thyrotoxic HPP is up to 20 times more common in men.6 In the familial
form, paralytic attacks are more frequent and more severe in men than in women.1 Some
researchers speculate that stimulation of ATPase activity by androgens may account for
the male predominance of the disorder.
Testing aids in the diagnosis of HPP and in the management of patients who have the
disorder. Overall, levels of creatine kinase and serum myoglobin are higher in patients
with HPP than in the patients' family members who do not have HPP.1 Muscle biopsies
show vacuolization and replacement of muscle tissue with fat in patients with HPP.1 In
one study,1 surface electromyograms showed characteristic changes in 87% of patients.
Computed tomography can be used to confirm myopathic changes and muscle damage.1
Patients with HPP generally have acute and reversible attacks. Approximately 40 fatal
cases of hypokalemia and periodic paralysis have been reported in the contemporary
medical literature.9 Deaths are attributed to cardiac failure or paralysis of the muscles of
respiration,9 although patients with HPP usually have a normal life span.10
Implications for Management
Several precipitating events contributed to the development of HPP in the patient
described in the case report. He was alkalotic, received corticosteroids, had fluid volume
loss, and had primary hyperthyroidism. In addition, he had recently experienced stress
related to occupational changes and had participated in heavy physical work.
When the underlying problem is ascertained, as with hyperthyroidism, the treatment of
choice centers on management of the causative disorder. In hyperthyroid patients, a
euthyroid state will relieve the paralysis of HPP. Propranolol is effective for relief of the
paralytic episodes and the thyrotoxic signs and symptoms related to the hyperadrenergic
state.6
Nonselective beta-adrenergic blockers can protect patients from paralytic attacks by
decreasing ATPase activity. In some patients, propranolol can reduce the frequency and
severity of attacks.2 In one case study," a patient had diffuse weakness and hypokalemia.
The diagnosis was thyrotoxic HPP, and potassium was administered. Serum potassium
levels did not improve, and the patient's clinical status worsened. After administration of
IV propranolol, the hypokalemia and paralysis immediately resolved. Treatment of
familial HPP is not as definitive as that of the secondary or acquired form. Although total
body potassium deficiency is not apparent, potassium replacement can be used to prevent
attacks of paralysis. Supplemental potassium is given orally if the patient can tolerate this
form of the electrolyte. Potassium supplementation is used cautiously because potassium
will be released from the cells once the paralysis subsides. Glucose solutions are avoided
because a hyperglycemic state augments the intracellular shift of potassium.4 The goal is
to prevent acute complications of hypokalemia and restore normal potassium stores
gradually.
Some evidence suggests that acetazolamide may decrease the severity of, decrease the
frequency of, and even prevent paralytic attacks.' Acetazolamide can improve muscle
strength by 50% and decrease the need for potassium supplementation.' Other diuretics,
such as potassium-sparing agents (spironolactone, amiloride hydrochloride, and
triamterene), may help resolve signs and symptoms related to HPP in some patients.1
Cardiac rhythm, serum potassium levels, electrolyte balance, and muscular changes must
be monitored. Education of patients focuses on promoting early interventions to prevent
catastrophic physiological changes. Mild exercise can abort an incipient paralytic attack
by moving potassium out of the intracellular compartment. Patients are encouraged to
avoid high-carbohydrate diets and to consume foods high in potassium. Patients should
be taught to be cautious with procedures involving anesthesia. Patients with HPP often
have postoperative episodes of hypokalemia and paralysis.
Although aware of complications related to electrolyte abnormalities, healthcare
providers rarely care for patients with severe hypokalemia that results in profound
physiological changes. Patients at risk for the development of paralytic attacks associated
with HPP require immediate intervention to prevent complications related to severe
potassium imbalance. An understanding of HPP and timely intervention are imperative in
the care of patients with this disorder.
[Reference]
REFERENCE
S

[Reference]
1. Links TP, Smit AJ, Molenaar WM, et al. Familial hypokalemic periodic paralysis:
clinical, diagnostic and therapeutic aspects. J Neurol Sci. 1994;122:33-43.
2. Ober KP. Thyrotoxic periodic paralysis in the United States: report of 7 cases and
review of the literature. Medicine. 1992;71:109-120.
3. DiBaise J. Thyrotoxic periodic paralysis. Iowa Med. 1995;85:291-292. Darrow M,
Brammer WK, Rowley A. Thyrotoxic periodic paralysis: two case studies. Arch Phys
Med Rehabil. 1995;76:685-687.
5. Fontaine B, Vale-Santos J, Jurkat-Rott K, et al. Mapping of the hypokalaemic periodic
paralysis (HypoPP) locus to chromosome Iq31-32 in three European families. Nat Genet.
1994;6:267-272.
6. Davison ET, Davison Mi. Triiodothyronine (T3) toxicosis with

[Reference]
hypokalemic periodic paralysis and ventricular tachycardia. J Electrocardiol.
1995;28:161-164.
7. Chia BL, Lee KH, Cheah JS. Sino-atrial Wenckebach conduction in thyrotoxic
periodic paralysis: a case report. Int J Cardiol. 1995;47:285-289.
8. Hoffman EP, Lehmann-Hom F, Rudel R. Overexcited or inactive: ion channels in
muscle disease. Cell. 1995;80:681-686. 9. Torabzadeh S, Greifenstein E, Rudick J,
Rutecki GW. Weight loss and bedtime weakness. Hosp Pract. 1994;29:57, 61.
10. Jurkat-Ron K, Lehmann-Hom F, Elbaz A, et al. A calcium channel mutation causing
hypokalemic periodic paralysis. Hum Mol Genet. 1994;3:1415-1419.
11. Shayne P, Hart A. Thyrotoxic periodic paralysis terminated with intravenous
propranolol. Ann Emerg Med.1994;24:736-740.

[Author Affiliation]
Reprint requests: InnoVision Communications, 101 Columbia, Aliso Viejo, CA 92656
Phone, (800) 899-1712 or (714) 362-2050 (ext 532); fax, (714) 3622022; e-mail,
ivcReprint@aol.com.

305 PQ REVERSE_CHRON 1284717171

Indexing (document details)

MeSH subjects: Adult, Diagnosis,
Differential, Electrocardiography, Humans, Hypokalemia --
complications, Hypokalemia -- diagnosis, Hypokalemia --
physiopathology, Male, Paralysis -- etiology, Paralysis --
physiopathology
Author(s): Kelley McKeta Anderson
Author Reprint requests: InnoVision Communications, 101 Columbia, Aliso
Affiliation: Viejo, CA 92656 Phone, (800) 899-1712 or (714) 362-2050 (ext 532);
fax, (714) 3622022; e-mail, ivcReprint@aol.com.
Document Case Reports
types:
Publication American Journal of Critical Care. Aliso Viejo: May
title: 1998. Vol. 7, Iss. 3; pg. 236, 4 pgs
Source type: Periodical
ISSN: 10623264
ProQuest 29392703
document ID:
Text Word 2021
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