[HSF] Heparin Induced Hyperkalemia due to Aldosterone inhibition

[Nasser F. Abou'Seada]

I know .... I know the feeling ... so now is the best time to write and
finish it .... tomorrow there are other cases ...

NFA

> -----Original Message-----
> From: openheart-l-bounces at lists.hsforum.com [mailto:openheart-l-
> bounces at lists.hsforum.com] On Behalf Of prasannasimha
> Sent: Saturday, November 04, 2006 1:14 PM
> To: OpenHeart-L at lists.hsforum.com
> Subject: Re: [HSF] Heparin Induced Hyperkalemia due to Aldosterone
inhibition
> 
> Lazy me will have to write it  :-)  and send it to the HSF journal. I
> have been promising myself to write at least 8 article in the last few
> years and somehow have been lazily been procrastinating despite all the
> data lying around and most of it being analyzed too !!
> Prasanna
> 
> Nasser F. Abou'Seada wrote:
> > Go on dear friend ... report your case ...
> >
> > NFA
> >
> >
> >> -----Original Message-----
> >> From: openheart-l-bounces at lists.hsforum.com [mailto:openheart-l-
> >> bounces at lists.hsforum.com] On Behalf Of prasannasimha
> >> Sent: Saturday, November 04, 2006 7:01 AM
> >> To: OpenHeart-L at lists.hsforum.com; ccm
> >> Subject: [HSF] Heparin Induced Hyperkalemia due to Aldosterone
inhibition
> >>
> >>
> >> Well, I did a literature search and guess what - the blessed thing is
well
> >>
> > documented -
> >
> >> Heparin induced hyperkalemia due to aldosterone inhibition.
> >> I did not know that Heparin can also cause priapism !!! Did you know
that
> >>
> > ????
> >
> >> Prasanna
> >>
> >>
> >> 1: Thromb Haemost. 2005 Nov;94(5):1109-10.
> >>
> >> Effect of unfractionated heparin and long-term treatment with
> >> low-molecular-weight heparin, bemiparin, on potassium levels.
> >>
> >> Rocha E, Gomez-Outes A, Martinez Gonzalez J, Kakkar VV.
> >>
> >> Publication Types:
> >>     Letter
> >>
> >> PMID: 16363259 [PubMed - indexed for MEDLINE]
> >>
> >> 2: Kaohsiung J Med Sci. 2005 Mar;21(3):128-33.
> >>
> >> Heparin-induced cardiac tamponade and life-threatening hyperkalema in a
> >>
> > patient
> >
> >> with chronic hemodialysis.
> >>
> >> Su HM, Voon WC, Chu CS, Lin TH, Lai WT, Sheu SH.
> >>
> >> Division of Cardiology, Department of Internal Medicine, Kaohsiung
Medical
> >> University, Kaohsiung, Taiwan.
> >>
> >> Heparin, a commonly used anticoagulant agent, is frequently used in
> >>
> > patients
> >
> >> undergoing hemodialysis. As with most medications, heparin has a
> >>
> > significant
> >
> >> side effect profile. Two of its most important side effects, _/*major
> >>
> > bleeding and
> >
> >> hyperkalemia, may be devastating without immediate diagnosis and
> >>
> > treatment.*/_
> >
> >> Major bleeding such as gastrointestinal, genitourinary or intracranial
> >>
> > bleeding
> >
> >> is occasionally encountered and rarely neglected. However,
heparin-induced
> >> cardiac tamponade is rarely encountered and may be easily overlooked.
> >>
> > Another
> >
> >> side effect, heparin-induced hyperkalemia, an unusual but
well-described
> >>
> > side
> >
> >> effect, is frequently forgotten until life-threatening arrhythmia has
> >>
> > occurred.
> >
> >> We report a case involving a 40-year-old male patient with uremia, who
had
> >> received heparin for 10 days for deep vein thrombosis in the left lower
> >> extremity. Hemopericardium with cardiac tamponade and life-threatening
> >> hyperkalemia were both noted in this patient.
> >>
> >> Publication Types:
> >>     Case Reports
> >>
> >> PMID: 15875438 [PubMed - indexed for MEDLINE]
> >>
> >> 3: Pharmacoepidemiol Drug Saf. 2004 May;13(5):299-302.
> >>
> >> Early onset of hyperkalemia in patients treated with low molecular
weight
> >> heparin: a prospective study.
> >>
> >> Koren-Michowitz M, Avni B, Michowitz Y, Moravski G, Efrati S, Golik A.
> >>
> >> Department of Medicine 'A', Assaf-Harofe Medical Center, Zerifin,
Israel.
> >> mayakoren at asaf.health.gov.il
> >>
> >> OBJECTIVE: Data on low molecular weight heparin (LMWH) and induction of
> >> hyperkalemia is scarce. Therefore, we conducted a prospective study
> >>
> > evaluating
> >
> >> potassium levels before and after three days of treatment with the LMWH
> >> Enoxaparin. METHODS: Patients treated with the LMWH Enoxaparin in the
> >>
> > standard
> >
> >> therapeutic dosages were included. Levels of potassium, sodium, urea,
> >> creatinine, AST, ALT bicarbonate, pH and platelet counts were examined
> >>
> > before
> >
> >> and after three days of LMWH treatment. Plasma renin activity (PRA) and
> >> aldosterone levels were examined in a subgroup of patients. Potassium
> >>
> > levels
> >
> >> were correlated with disease states and medications known to affect
> >>
> > potassium
> >
> >> homeostasis. RESULTS: Ninety-seven consecutive patients were enrolled
in
> >>
> > the
> >
> >> study, however, 12 patients were excluded from analysis; therefore 85
> >>
> > patients
> >
> >> comprised the study group. The most common reason for exclusion (in 9
> >>
> > patients)
> >
> >> was the absence of a second potassium result. We found an increase in
> >>
> > potassium
> >
> >> levels from 4.26 +/- 0.04 mmol/L at baseline to 4.43 +/- 0.04 mmol/L on
> >>
> > the
> >
> >> third day of treatment (mean +/- SE), with potassium levels exceeding
5.0
> >>
> > mmol/L
> >
> >> in 9% of treated patients. There was no life threatening or symptomatic
> >> hyperkalemia. PRA and aldosterone levels did not change significantly
> >>
> > during the
> >
> >> treatment period. There was no correlation between the increase in
> >>
> > potassium
> >
> >> levels and diabetes mellitus or treatment with angiotensin converting
> >>
> > enzymes
> >
> >> inhibitors, angiotensin receptor blockers, beta-blockers and
non-potassium
> >> sparing diuretics. CONCLUSIONS: _*Potassium levels increase on the
third
> >>
> > day of
> >
> >> treatment with the LMWH Enoxaparin. This effect may be aldosterone
> >>
> > independent.*_
> >
> >> Copyright 2003 John Wiley & Sons, Ltd.
> >>
> >> Publication Types:
> >>     Clinical Trial
> >>
> >> PMID: 15133781 [PubMed - indexed for MEDLINE]
> >>
> >> 4: Ann Pharmacother. 2004 Mar;38(3):404-7. Epub 2004 Jan 12.
> >>
> >> Heparin-induced hyponatremia.
> >>
> >> Norman NE, Sneed AM, Brown C, Ellis CA, Minard G, Brown RO.
> >>
> >> Department of Pharmacy, The Regional Medical Center at Memphis, TN
> >>
> > 38103-2807,
> >
> >> USA. enorman at the-med.org
> >>
> >> OBJECTIVE: To report a case of hyponatremia in a patient receiving
> >>
> > systemic
> >
> >> unfractionated heparin (UFH) therapy and parenteral nutrition. CASE
> >>
> > SUMMARY: A
> >
> >> 70-year-old African American woman was started on parenteral nutrition
for
> >> postoperative ileus following an elective surgical procedure. Three
days
> >>
> > later,
> >
> >> she was diagnosed with a pulmonary embolism and intravenous UFH therapy
> >>
> > was
> >
> >> initiated. During the 7-day course of UFH therapy, the patient's serum
> >>
> > sodium
> >
> >> concentration steadily declined and urine sodium concentration
> >>
> > progressively
> >
> >> increased. Physical examination revealed no signs or symptoms of hypo-
or
> >> hypervolemia. The patient's serum potassium concentration increased
> >>
> > modestly,
> >
> >> although significant hyperkalemia was not observed. After
discontinuation
> >>
> > of
> >
> >> UFH, serum concentrations of both sodium and potassium returned to
> >>
> > baseline
> >
> >> levels. DISCUSSION: Although heparin-induced hyperkalemia is well
> >>
> > documented,
> >
> >> cases associated with substantial hyponatremia have been reported less
> >> frequently. An objective causality assessment revealed that the adverse
> >>
> > drug
> >
> >> reaction was probable in this case. Hyponatremia and hyperkalemia
result
> >>
> > from
> >
> >> the antagonism of aldosterone by UFH within the zona glomerulosa of the
> >>
> > adrenal
> >
> >> glands. CONCLUSIONS: _*The use of UFH may result in significant
> >>
> > hyponatremia as
> >
> >> well as hyperkalemia. Reversal of these electrolyte disturbances occurs
> >>
> > after
> >
> >> discontinuation of heparin.*_
> >>
> >> Publication Types:
> >>     Case Reports
> >>
> >> PMID: 14742828 [PubMed - indexed for MEDLINE]
> >>
> >> 5: Eur J Clin Pharmacol. 2003 Sep;59(5-6):373-7. Epub 2003 Jul 8.
> >>
> >> Variations of serum potassium level and risk of hyperkalemia in
inpatients
> >> receiving low-molecular-weight heparin.
> >>
> >> Gheno G, Cinetto L, Savarino C, Vellar S, Carraro M, Randon M.
> >>
> >> Department of Internal Medicine, ASL 3 of the Veneto Region, Bassano
del
> >>
> > Grappa,
> >
> >> Italy. giuseppe.gheno at aslbassano.it
> >>
> >> OBJECTIVES. To observe the variations of serum potassium level in
patients
> >> receiving low-molecular weight heparin, assess the consequent risk of
> >> hyperkalemia and evaluate the clinical contributory factors. METHODS. A
> >> prospective study was performed on consecutive inpatients treated with
> >> low-molecular-weight heparin as indicated by the attending physicians.
The
> >> changes of serum potassium level observed within 5-8 days were tested
by
> >> univariate and multivariate analysis according to demographic and
clinical
> >> variables and concomitant pharmacological therapy. RESULTS. Four
hundred
> >>
> > and
> >
> >> sixteen patients (mean age 73 years; 64% female) were enrolled in the
> >>
> > study over
> >
> >> 15 months. After receiving nadroparin or enoxaparin (mean daily dosage:
> >>
> > 76.3
> >
> >> anti-factor Xa unit/kg) for a median 6-day period, their mean (+/-SD)
> >>
> > serum
> >
> >> potassium level increased from 4.2+/-0.5 mmol/l to 4.5+/-0.5 mmol/l (
> >>
> > P<0.0001).
> >
> >> This change was significantly correlated with baseline potassium,
interval
> >> between potassium samplings, history of hypertension or renal
> >>
> > insufficiency, and
> >
> >> marginally with aldosterone antagonist treatment. Hyperkalemia, defined
as
> >> potassium exceeding 5.5 mmol/l, developed in ten patients (2.4%) and
the
> >>
> > highest
> >
> >> value observed was 7.6 mmol/l; by multivariate logistic-regression
> >>
> > analysis,
> >
> >> history of diabetes was the only significant independent predictor
(odds
> >>
> > ratio
> >
> >> 6.5; 95% C.I.=1.7-24.8). CONCLUSION. _*Short-term treatment with
> >> low-molecular-weight heparin induces a significant increase in serum
> >>
> > potassium
> >
> >> level but the related incidence of relevant hyperkalemia is low.
However,
> >>
> > given
> >
> >> the high absolute number of patients currently exposed to the risk in
many
> >> clinical settings and the limitation of risk prediction, clinicians
should
> >> prevent this life-threatening complication by a high index of suspicion
> >>
> > and,
> >
> >> accordingly, a quite routine monitoring of serum potassium.*_
> >>
> >> Publication Types:
> >>     Clinical Trial
> >>
> >> PMID: 12851802 [PubMed - indexed for MEDLINE]
> >>
> >> 6: Clin Med. 2003 Jan-Feb;3(1):87.
> >>
> >> Serious hyperkalaemia after short use of low molecular weight heparin
in a
> >> diabetic patient.
> >>
> >> Rippin JD, Hado HS, Green N, Elhadd TA.
> >>
> >> Publication Types:
> >>     Case Reports
> >>     Letter
> >>
> >> PMID: 12617429 [PubMed - indexed for MEDLINE]
> >>
> >> 7: Ann Thorac Surg. 2002 Nov;74(5):1698-700.
> >>
> >> Heparin-induced hyperkalemia after cardiac surgery.
> >>
> >> Day JR, Chaudhry AN, Hunt I, Taylor KM.
> >>
> >> Department of Cardiothoracic Surgery, Hammersmith Hospital, London,
United
> >> Kingdom. j.day at ic.ac.uk
> >>
> >> Surgeons are increasingly faced with patients suffering from
complicated
> >> pathology in multiple organ systems, to which multiple therapeutic
agents
> >>
> > with
> >
> >> complex adverse effects are often prescribed. We face a daily challenge
in
> >> maintaining an up-to-date knowledge of these complications. Heparin is
> >>
> > widely
> >
> >> used in surgical practice, yet our awareness of its adverse effects,
other
> >>
> > than
> >
> >> bleeding and thrombocytopenia, remains poor. We will _*present an
example
> >>
> > of
> >
> >> heparin-induced hyperkalemia following administration for
cardiopulmonary
> >>
> > bypass
> >
> >> and intraaortic balloon pump prophylaxis. This is a rare but serious
> >> complication of heparin therapy, not usually reported in the context of
a
> >> cardiac surgical patient*_. We will also discuss the renal physiology
> >>
> > leading to
> >
> >> hyperkalemia and the options available for its management.
> >>
> >> Publication Types:
> >>     Case Reports
> >>
> >> PMID: 12440638 [PubMed - indexed for MEDLINE]
> >>
> >> 8: Pathophysiol Haemost Thromb. 2002 May-Jun;32(3):107-10.
> >>
> >> Effect of low-molecular-weight heparin on potassium homeostasis.
> >>
> >> Abdel-Raheem MM, Potti A, Tadros S, Koka V, Hanekom D, Fraiman G,
> >>
> > Danielson BD.
> >
> >> Department of Medicine, University of North Dakota School of Medicine,
> >>
> > Fargo, N
> >
> >> Dak 58102, USA.
> >>
> >> Background: Low-molecular-weight heparins (LMWHs) are being preferred
to
> >> unfractionated heparin (UFH) because of their superior convenience and
a
> >> comparable or slightly better toxicity profile. Whether LMWH has an
> >>
> > inhibitory
> >
> >> effect on aldosterone that causes hyperkalemia is yet uncertain.
Methods:
> >> Twenty-eight patients (all male; mean age: 70 years, range 52-87 years)
> >>
> > placed
> >
> >> on LMWH therapy (40 mg subcutaneously every 12 h) for deep venous
> >>
> > thrombosis
> >
> >> prophylaxis after an operation were included in the study. Transtubular
> >> potassium concentration gradient (TTKG) was calculated 1 day prior to
LMWH
> >> therapy and again after 4 days of treatment. Of the 28 patients
enrolled
> >>
> > in the
> >
> >> study, we were able to calculate the TTKG in only 19 patients: 9 had a
> >>
> > urinary
> >
> >> osmolarity (either before or after LMWH therapy) less than the serum
> >>
> > osmolarity,
> >
> >> making the TTKG calculation unreliable. The Wilcoxon signed-rank test
was
> >>
> > used
> >
> >> to analyze differences in the median serum potassium levels and TTKG
> >>
> > before and
> >
> >> after LMWH therapy. Results: All patients had adequate renal function
> >> (creatinine clearance >90 ml/min). _*Mean (+/- SD) serum potassium
> >>
> > concentration
> >
> >> before LMWH was 4.25 (+/- 0.40) mmol/dl. It increased to 4.35 (+/-
0.41)
> >>
> > mmol/dl
> >
> >> after initiating LMWH therapy (p = 0.09). Similarly, the mean (+/- SD)
> >>
> > TKKG
> >
> >> calculated was 5.52 (+/- 2.33) before and 5.97 (+/- 3.06) after 4 days
of
> >>
> > LMWH
> >
> >> (p = 0.54). Conclusions: Unlike UFH, LMWH (**Lovenox in doses used for
> >> postoperative prophylaxis against deep venous thrombosis does not seem
to
> >>
> > have a
> >
> >> significant effect on potassium homeostasis.*_ Copyright 2002 S. Karger
> >>
> > AG, Basel
> >
> >> PMID: 12372922 [PubMed - indexed for MEDLINE]
> >>
> >> 9: Ann Ital Med Int. 2002 Jan-Mar;17(1):51-3.
> >>
> >> Heparin-induced life-threatening hyperkalemia.
> >>
> >> Gheno G, Savarino C, Vellar S, Cinetto L.
> >>
> >> Departimento di Medicina Interna, Ospedale Civile di Asiago, ASL 3
Regione
> >> Veneto di Bassano del Grappa (VI). giuseppe.gheno at tin.it
> >>
> >> Hyperkalemia may occur in many clinical settings and lead to serious
> >>
> > events.
> >
> >> Heparin-induced hyperkalemia is presumably less well recognized than
other
> >> untoward effects of heparin treatment and more frequent than commonly
> >>
> > perceived.
> >
> >> To draw attention to this clinically relevant occurrence, we report 2
> >>
> > cases of
> >
> >> life-threatening bradyarrhythmia associated with heparin prescription.
> >> _*Heparin-induced hyperkalemia is mediated by an enzymatic block in the
> >>
> > synthesis
> >
> >> of aldosterone; however, in most cases severe hyperkalemia occurs in
the
> >> presence of additional factors influencing potassium homeostasis.*_
> >>
> > Patients
> >
> >> treated with heparin should be stratified and adequately monitored
> >>
> > according to
> >
> >> the outlined risk profile.
> >>
> >> Publication Types:
> >>     Case Reports
> >>
> >> PMID: 11975115 [PubMed - indexed for MEDLINE]
> >>
> >> 10: Ann Pharmacother. 2000 May;34(5):606-10.
> >>
> >> Fludrocortisone for the treatment of heparin-induced hyperkalemia.
> >>
> >> Sherman DS, Kass CL, Fish DN.
> >>
> >> Department of Pharmacy Practice, School of Pharmacy, University of
> >>
> > Colorado
> >
> >> Health Sciences Center, Denver, USA.
> >>
> >> OBJECTIVE: To report the use of fludrocortisone for heparin-induced
> >>
> > hyperkalemia
> >
> >> and to briefly review the available literature relating to
heparin-induced
> >> hyperkalemia. CASE SUMMARY: A 34-year-old African-American man was
> >>
> > admitted to
> >
> >> the hospital for pneumococcal pneumonia and sepsis. His hospital course
> >>
> > was
> >
> >> complicated by the development of acute respiratory distress syndrome,
> >>
> > severe
> >
> >> sepsis, acute renal failure, placement of a tracheostomy, and recurrent
> >> nasopharyngeal bleeding. The patient also developed a subclavian vein
> >>
> > thrombosis
> >
> >> with extension to the cephalic and basilic veins secondary to placement
of
> >>
> > a
> >
> >> pulmonary artery catheter; anticoagulation with heparin was required.
On
> >>
> > day 9
> >
> >> of heparin therapy, the patient developed symptomatic hyperkalemia
> >>
> > refractory to
> >
> >> conventional therapies. Oral fludrocortisone 0.1 mg/d was initiated
with
> >> resolution of the hyperkalemia within 24 hours despite the continued
> >> administration of heparin. DATA SOURCES: A MEDLINE (1966-October 1999)
> >>
> > search
> >
> >> was performed to identify case reports and clinical trials discussing
> >> heparin-induced hyperkalemia or the use of fludrocortisone for
> >>
> > hyperkalemia.
> >
> >> DISCUSSION: _*Heparin has the potential to induce hyperkalemia by
several
> >> mechanisms, including decreased aldosterone synthesis, reduction in
number
> >>
> > and
> >
> >> affinity of aldosterone II receptors, and atrophy of the renal zona
> >>
> > glomerulosa.
> >
> >> Fludrocortisone promotes potassium excretion by its direct actions on
the
> >>
> > renal
> >
> >> distal tubules.*_ In this patient, fludrocortisone resulted in a
> >>
> > significant and
> >
> >> rapid decrease in serum potassium even with continued heparin
> >>
> > administration and
> >
> >> acute renal failure. CONCLUSIONS: This case suggests that
fludrocortisone
> >>
> > is a
> >
> >> reasonable alternative therapy for patients with hyperkalemia secondary
to
> >> heparin therapy when the continued administration of heparin is
necessary.
> >>
> >> Publication Types:
> >>     Case Reports
> >>
> >> PMID: 10852087 [PubMed - indexed for MEDLINE]
> >>
> >> 11: Clin Appl Thromb Hemost. 1999 Oct;5 Suppl 1:S7-15.
> >>
> >> Clinical aspects of heparin-induced thrombocytopenia and thrombosis and
> >>
> > other
> >
> >> side effects of heparin therapy.
> >>
> >> Bick RL, Frenkel EP.
> >>
> >> University of Texas Southwestern Medical Center, USA.
> >>
> >> Heparin, first used to prevent the clotting of blood in vitro, has been
> >> clinically used to treat thrombosis for more than 50 years. Although
> >>
> > several new
> >
> >> anticoagulant drugs are in development, heparin remains the
anticoagulant
> >>
> > of
> >
> >> choice to treat acute thrombotic episodes. The clinical effects of
heparin
> >>
> > are
> >
> >> meritorious, but side effects do exist. Bleeding is the primary
untoward
> >>
> > effect
> >
> >> of heparin. Major bleeding is of primary concern in patients receiving
> >>
> > heparin
> >
> >> therapy. However, additional important untoward effects o_*f heparin
> >>
> > therapy
> >
> >> include heparin-induced thrombocytopenia, heparin-associated
osteoporosis,
> >> eosinophilia, skin reactions, allergic reactions other than
> >>
> > thrombocytopenia,
> >
> >> alopecia, transaminasemia, hyperkalemia, hypoaldosteronism, and
> >>
> > priapism.*_ These
> >
> >> side effects are relatively rare in a given individual, but given the
> >>
> > extremely
> >
> >> widespread use of heparin, some are quite common, particularly HITT and
> >> osteoporosis. Although reasonable incidences of many of these side
effects
> >>
> > can
> >
> >> be "softly" deduced from current reports dealing with unfractionated
> >>
> > heparin, at
> >
> >> present the incidences of these side effects with newer low molecular
> >>
> > weight
> >
> >> heparins appear to be much less common. However, only longer experience
> >>
> > will
> >
> >> more clearly define the incidence of each side effect with low
molecular
> >>
> > weight
> >
> >> preparations.
> >>
> >> Publication Types:
> >>     Review
> >>
> >> PMID: 10726030 [PubMed - indexed for MEDLINE]
> >>
> >> 12: Am J Phys Med Rehabil. 2000 Jan-Feb;79(1):93-6.
> >>
> >> Heparin-induced hyperkalemia confirmed by drug rechallenge.
> >>
> >> Orlando MP, Dillon ME, O'Dell MW.
> >>
> >> Department of Internal Medicine, University of Cincinnatti College of
> >>
> > Medicine,
> >
> >> Ohio, USA.
> >>
> >> Subcutaneous heparin is commonly used as a prophylaxis against deep
venous
> >> thrombosis in a wide variety of hospitalized patients. As with most
> >>
> > medications,
> >
> >> _*heparin has a significant side effect profile; heparin-induced
> >>
> > hyperkalemia is
> >
> >> an unusual but well described side effect*_. To increase awareness of
> >> heparin-induced hyperkalemia and of those patients at greatest risk, we
> >>
> > present
> >
> >> two cases of documented hyperkalemia induced by heparin and reconfirmed
by
> >>
> > drug
> >
> >> rechallenge.
> >>
> >> PMID: 10678609 [PubMed - indexed for MEDLINE]
> >>
> >> 13: Am J Ther. 1998 Mar;5(2):125-32.
> >>
> >> University of Miami Division of Clinical Pharmacology therapeutic
rounds:
> >> drug-induced hyperkalemia.
> >>
> >> Preston RA, Hirsh MJ MD, Oster MD Jr, Oster HR MD.
> >>
> >> Department of Medicine, University of Miami School, 1500 NW 12th Ave,
15th
> >>
> > Floor
> >
> >> West, Miami, Florida 33136, USA.
> >>
> >> Drug-induced hyperkalemia is an important but often overlooked problem
> >> encountered commonly in clinical practice. It may occur in the
ambulatory
> >>
> > as
> >
> >> well as the impatient setting. Every evaluation of a hyperkalemic
patient
> >>
> > should
> >
> >> include a careful review of medications to determine if a drug capable
of
> >> causing or aggravating hyperkalemia is present. Medications generally
> >>
> > produce
> >
> >> hyperkalemia either by causing redistribution of potassium (beta2
> >>
> > -adrenergic
> >
> >> blockers, succinylcholine, digitalis overdose, hypertonic mannitol) or
by
> >> impairing renal potassium excretion. Drugs cause impaired renal
potassium
> >> excretion by (1) interfering with the production and/or secretion of
> >>
> > aldosterone
> >
> >> (nonsterodial anti-inflammatory drugs, angiotensin-converting enzyme
> >>
> > inhibitors,
> >
> >> angiotensin-II receptor antagonists, heparin, cyclosporine, and FK 506)
or
> >>
> > (2)
> >
> >> blocking the kaliuretic effects of aldosterone (potassium-sparing
> >>
> > diuretics,
> >
> >> trimethoprim, pentamidine, and nefamostat mesilate). Because severe
renal
> >> insufficeiency is generally required to cause hyperkalemia, an elevated
> >>
> > serum
> >
> >> potassium concentration in a patient with mild-to-moderate renal
failure
> >>
> > should
> >
> >> not be ascribed to renal failure alone._* A careful search for "hidden"
> >>
> > potassium
> >
> >> loads and for causes of impaired tubular secretion of potassium
(including
> >> drugs) is necessary. Finally, it is important to recognize that the
causes
> >>
> > of
> >
> >> hyperkalemia may be additive. Patients may have more than one cause of
> >> hyperkalemia at the same time. Therefore, all potential causes of
> >>
> > hyperkalemia,
> >
> >> including drugs, should be systematically evaluated in every
hyperkalemic
> >> patient.*_
> >>
> >> Publication Types:
> >>     Case Reports
> >>
> >> PMID: 10099101 [PubMed - indexed for MEDLINE]
> >>
> >> 14: Artif Organs. 1998 Jul;22(7):614-7.
> >>
> >> Heparin-induced hyperkalemia in chronic hemodialysis patients:
comparison
> >>
> > of low
> >
> >> molecular weight and unfractionated heparin.
> >>
> >> Hottelart C, Achard JM, Moriniere P, Zoghbi F, Dieval J, Fournier A.
> >>
> >> Service de Nephrologie, Medecine Interne, CHU Amiens, France.
> >>
> >> Aldosterone suppression and subsequent hyperkalemia are well described
> >> reversible side effects of prolonged treatment with heparin. This study
> >>
> > was
> >
> >> designed to examine whether the discontinuous use of heparin three
times a
> >>
> > week
> >
> >> to prevent thrombosis formation during hemodialysis sessions could also
> >>
> > induce
> >
> >> hypoaldosteronism and might contribute to increased predialysis kalemia
in
> >> hemodialysis patients. Two different heparinization regimens were
> >>
> > prospectively
> >
> >> compared in a crossover study of 11 chronic hemodialysis patients.
During
> >>
> > 2
> >
> >> consecutive weeks, the patients were dialyzed each week with either
their
> >>
> > usual
> >
> >> doses of unfractionated heparin (UH) (6,160 IU +/- 1,350 IU) or low
> >>
> > molecular
> >
> >> weight heparin (LMWH) (15 anti-Xa activity [aXa] U/kg + 5 aXa U/kg/h).
In
> >>
> > all
> >
> >> but 2 patients, the predialysis level of plasma K+ was higher with UH
than
> >>
> > with
> >
> >> LMWH, and the mean value was higher (5.66+/-0.83 versus 5.15+/-0.68 mM,
p
> >>
> > =
> >
> >> 0.01) while no differences in the predialysis plasma concentrations of
> >> creatinine, phosphate, urea, and bicarbonate were observed, excluding
the
> >> potential role of differences in diet and dialysis efficacy in
explaining
> >>
> > the
> >
> >> higher plasma K+ concentration with UH. The mean plasma aldosterone to
> >>
> > plasma
> >
> >> renin activity (pRA) ratio was higher with LMWH than with UH
> >>
> > (149.54+/-123.1
> >
> >> versus 111.91+/-86.22 pg/ng/ h, p < 0.05). Individual plasma
aldosterone
> >>
> > values
> >
> >> were found to be correlated to pRAs both during the UH period and the
LMWH
> >> period, and the slope of the positive linear relation between plasma
> >>
> > aldosterone
> >
> >> and pRA was lower during the UH treatment period (63 versus 105
pg/ng/h).
> >> Finally, a negative linear correlation was found between the
differences
> >>
> > in
> >
> >> individual predialysis plasma K+ observed during the 2 protocols and
the
> >> differences in the corresponding plasma aldosterone levels, suggesting
a
> >>
> > link
> >
> >> between the higher kalemia and the lower aldosterone responsiveness to
> >> angiotensin with unfractionated heparin. Although it cannot be
concluded
> >>
> > whether
> >
> >> or not LMWH inhibits aldosterone synthesis, _*should LMWH decrease
> >>
> > aldosterone
> >
> >> production, this side effect is 33% less marked than that of UH so that
> >>
> > the
> >
> >> predialysis plasma K+ levels are 10% lower. This property makes LMWH
use
> >> preferable to that of UH in patients with elevated predialysis
kalemia.*_
> >>
> >> Publication Types:
> >>     Clinical Trial
> >>     Controlled Clinical Trial
> >>
> >> PMID: 9684701 [PubMed - indexed for MEDLINE]
> >>
> >> 15: QJM. 1997 Nov;90(11):725.
> >>
> >> Comment on:
> >>     QJM. 1997 Jul;90(7):487-92.
> >>
> >> Heparin-induced disturbance of potassium homeostasis.
> >>
> >> Bacon NC.
> >>
> >> Publication Types:
> >>     Comment
> >>     Letter
> >>
> >> PMID: 9474355 [PubMed - indexed for MEDLINE]
> >>
> >> 16: Lancet. 1997 Jul 26;350(9073):292-3.
> >>
> >> Comment on:
> >>     Lancet. 1997 May 17;349(9063):1447-8.
> >>
> >> Effect of low-molecular-weight heparin on serum concentrations of
> >>
> > potassium.
> >
> >> Wiggam MI, Beringer TR.
> >>
> >> Publication Types:
> >>     Case Reports
> >>     Comment
> >>     Letter
> >>
> >> PMID: 9242823 [PubMed - indexed for MEDLINE]
> >>
> >> 17: Postgrad Med J. 1997 Jul;73(861):433-4.
> >>
> >> Hospital-acquired hyperkalaemia.
> >>
> >> Bacon NC.
> >>
> >> Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK.
> >>
> >> Publication Types:
> >>     Case Reports
> >>
> >> PMID: 9338034 [PubMed - indexed for MEDLINE]
> >>
> >> 18: Miner Electrolyte Metab. 1997;23(1):58-61.
> >>
> >> A case of 'reverse' pseudohyperkalemia.
> >>
> >> Singh PJ, Zawada ET, Santella RN.
> >>
> >> Department of Internal Medicine, University of South Dakota School of
> >>
> > Medicine,
> >
> >> Sioux Falls 57105-1570, USA.
> >>
> >> Pseudohyperkalemia is diagnosed when the serum potassium level exceeds
the
> >> plasma potassium level by 0.4 mmol/l. This is commonly encountered in
> >>
> > settings
> >
> >> of high leukocyte or platelet counts, since under these conditions,
> >>
> > potassium,
> >
> >> an intracellular cation, is released in supranormal amounts during the
> >>
> > process
> >
> >> of clotting. We report an unusual case wherein the reverse was true,
i.e.,
> >>
> > the
> >
> >> plasma potassium concentrations was higher than that found in the
serum.
> >> Heparin, which is known to cause cell lysis, was used as the
> >>
> > anti-coagulant in
> >
> >> the plasma tubes. We propose that the underlying mechanism in this
> >>
> > particular
> >
> >> case is a heightened sensitivity to heparin-induced membrane damage in
the
> >>
> > face
> >
> >> of a hematological malignancy.
> >>
> >> Publication Types:
> >>     Case Reports
> >>
> >> PMID: 9058371 [PubMed - indexed for MEDLINE]
> >>
> >> 19: JPEN J Parenter Enteral Nutr. 1996 Nov-Dec;20(6):429-32.
> >>
> >> Hyperkalemia secondary to concurrent pharmacotherapy in a patient
> >>
> > receiving home
> >
> >> parenteral nutrition.
> >>
> >> Brown RO, Hamrick KD, Dickerson RN, Lee N, Parnell DH Jr, Kudsk KA.
> >>
> >> Department of Clinical Pharmacy, University of Tennessee, Memphis
38163,
> >>
> > USA.
> >
> >> We report a case of probable combined octreotide- and heparin-induced
> >> hyperkalemia. The patient had been receiving home parenteral nutrition,
> >> enoxaparin, and octreotide for 10 months. She required very little
> >>
> > potassium in
> >
> >> her PN solution to maintain serum potassium concentrations in the
normal
> >>
> > range.
> >
> >> The patient reportedly did not receive other medications or have
clinical
> >> conditions that, to our knowledge, cause hyperkalemia. She maintained
> >>
> > normal
> >
> >> renal function throughout the hospitalization and did not appear to
have
> >>
> > any
> >
> >> significant acid-base disorders. _*Practitioners should be aware of the
> >>
> > potential
> >
> >> for octreotide and heparin to cause hyperkalemia*_. Regular monitoring
of
> >>
> > serum
> >
> >> potassium concentrations should be done for patients receiving
octreotide
> >>
> > and
> >
> >> heparin to avoid hyperkalemia.
> >>
> >> Publication Types:
> >>     Case Reports
> >>
> >> PMID: 8950745 [PubMed - indexed for MEDLINE]
> >>
> >> 20: Am J Med. 1995 Jun;98(6):575-86.
> >>
> >> Heparin-induced aldosterone suppression and hyperkalemia.
> >>
> >> Oster JR, Singer I, Fishman LM.
> >>
> >> Medical Service, Department of Veterans Affairs Medical Center, Miami,
> >>
> > Florida
> >
> >> 33125, USA.
> >>
> >> PURPOSE: To review the effects of heparin and heparinoid compounds on
> >> aldosterone physiology and associated induction of hyperkalemia.
MATERIALS
> >>
> > AND
> >
> >> METHODS: A comprehensive literature search (of human and animal data)
was
> >> carried out by computer and by using reference citations from primary
> >>
> > sources.
> >
> >> RESULTS: *_Heparin and its congeners are predictable, potent inhibitors
of
> >> aldosterone production. This inhibitory effect is specific for the zona
> >> glomerulosa; other corticosteroids are not affected. Aldosterone
> >>
> > suppression
> >
> >> occurs within a few days of initiation of therapy, is reversible, and
is
> >> independent of either anticoagulant effect or route of administration.
> >>
> > Decreases
> >
> >> in aldosterone levels may occur with heparin dosages as low as 5,000 U
> >>
> > BID. The
> >
> >> most important, but probably not the only mechanism of aldosterone
> >>
> > inhibition
> >
> >> appears to involve reduction in both the number and affinity of the
> >> angiotensin-II receptors in the zona glomerulosa. Prolonged use of
heparin
> >> causes marked reduction in the width of the adrenal zona glomerulosa.
> >> CONCLUSIONS: Aldosterone suppression results in natriuresis and less
> >>
> > predictably
> >
> >> in decreased excretion of potassium. Greater than normal serum
potassium
> >>
> > levels
> >
> >> occur in about 7% of patients, but marked hyperkalemia generally
requires
> >>
> > the
> >
> >> presence of additional factors perturbing potassium balance (in
> >>
> > particular,
> >
> >> renal insufficiency, diabetes mellitus, or the use of certain
> >>
> > medications).
> >
> >> Heparin-induced increases in serum potassium need to be better
anticipated
> >>
> > by
> >
> >> clinicians. Serum potassium levels should be monitored periodically in
> >>
> > patients
> >
> >> being given heparin for 3 or more days, and in patients at relatively
high
> >>
> > risk
> >
> >> for hyperkalemia, the monitoring interval should probably be no greater
> >>
> > than 4
> >
> >> days._
> >> *
> >> Publication Types:
> >>     Review
> >>
> >> PMID: 7778574 [PubMed - indexed for MEDLINE]
> >>
> >> 1: Am J Med. 1995 Jun;98(6):575-86.
> >>
> >> Heparin-induced aldosterone suppression and hyperkalemia.
> >>
> >> Oster JR, Singer I, Fishman LM.
> >>
> >> Medical Service, Department of Veterans Affairs Medical Center, Miami,
> >>
> > Florida
> >
> >> 33125, USA.
> >>
> >> PURPOSE: To review the effects of heparin and heparinoid compounds on
> >> aldosterone physiology and associated induction of hyperkalemia.
MATERIALS
> >>
> > AND
> >
> >> METHODS: A comprehensive literature search (of human and animal data)
was
> >> carried out by computer and by using reference citations from primary
> >>
> > sources.
> >
> >> RESULTS: Heparin and its congeners are predictable, potent inhibitors
of
> >> aldosterone production. This inhibitory effect is specific for the zona
> >> glomerulosa; other corticosteroids are not affected. Aldosterone
> >>
> > suppression
> >
> >> occurs within a few days of initiation of therapy, is reversible, and
is
> >> independent of either anticoagulant effect or route of administration.
> >>
> > Decreases
> >
> >> in aldosterone levels may occur with heparin dosages as low as 5,000 U
> >>
> > BID. The
> >
> >> most important, but probably not the only mechanism of aldosterone
> >>
> > inhibition
> >
> >> appears to involve reduction in both the number and affinity of the
> >> angiotensin-II receptors in the zona glomerulosa. Prolonged use of
heparin
> >> causes marked reduction in the width of the adrenal zona glomerulosa.
> >> CONCLUSIONS: Aldosterone suppression results in natriuresis and less
> >>
> > predictably
> >
> >> in decreased excretion of potassium. _*Greater than normal serum
potassium
> >>
> > levels
> >
> >> occur in about 7% of patients, but marked hyperkalemia generally
requires
> >>
> > the
> >
> >> presence of additional factors perturbing potassium balance (in
> >>
> > particular,
> >
> >> renal insufficiency, diabetes mellitus, or the use of certain
> >>
> > medications).
> >
> >> Heparin-induced increases in serum potassium need to be better
anticipated
> >>
> > by
> >
> >> clinicians. Serum potassium levels should be monitored periodically in
> >>
> > patients
> >
> >> being given heparin for 3 or more days, and in patients at relatively
high
> >>
> > risk
> >
> >> for hyperkalemia, the monitoring interval should probably be no greater
> >>
> > than 4
> >
> >> days.
> >> *_
> >> Publication Types:
> >>     Review
> >>
> >> PMID: 7778574 [PubMed - indexed for MEDLINE]
> >>
> >> 2: Thromb Res. 1992 Jun 1;66(5):467-73.
> >>
> >> Dose dependent suppression of mineralocorticoid metabolism by different
> >>
> > heparin
> >
> >> fractions.
> >>
> >> Siebels M, Andrassy K, Vecsei P, Seelig HP, Back T, Nawroth P, Weber E.
> >>
> >> Department Medicine, University Hospital, Heidelberg, Germany.
> >>
> >> One neglected side effect of heparin therapy is the inhibition of
adrenal
> >> aldosterone production leading to occasionally life-threatening
> >>
> > hyperkalaemia.
> >
> >> This is only reported with (therapeutic) high doses (greater than or
equal
> >>
> > to
> >
> >> 20.000 IU). The complex interplay of mineralocorticoid metabolites was
> >>
> > studied
> >
> >> in 29 subjects with unfractionated (UFH) and low molecular weight
heparin
> >> (LMWH). Both heparins altered mineralocorticoid metabolism in a dose
> >>
> > dependent
> >
> >> manner. Whereas no effect was observed with UFH 2 x 5000 IU sc/day or
LMWH
> >>
> > 2500
> >
> >> a FXa U sc/day, higher doses significantly suppressed aldosterone and
> >> 18-hydroxycorticosterone production in plasma and urine. Three out of
> >>
> > seven
> >
> >> patients receiving UFH 3 x 7500 IU sc/day developed hyperkalaemia. This
> >>
> > study
> >
> >> shows the _*threshold dosage of UFH leading to suppression of
> >>
> > mineralocorticoid
> >
> >> metabolism in man and provides information that LMWH as well as UFH can
> >>
> > suppress
> >
> >> mineralocorticoid production*_. With respect to therapeutic
implications
> >>
> > it is
> >
> >> important that LMWH at 2500 a FXa U sc/d had no effect on
> >>
> > mineralocorticoid
> >
> >> metabolism in contrast to UFH at a dosage currently used for prevention
of
> >> thromboembolism (3 x 5000 IU sc/d).
> >>
> >> PMID: 1326134 [PubMed - indexed for MEDLINE]
> >>
> >> 3: Eur J Clin Pharmacol. 1992;43(2):185-7.
> >>
> >> A low molecular weight heparin decreases plasma aldosterone in patients
> >>
> > with
> >
> >> primary hyperaldosteronism.
> >>
> >> Cailleux N, Moore N, Levesque H, Courtois H, Godin M.
> >>
> >> Department of Nephrology, CHU de Rouen, Boisguillaume, France.
> >>
> >> Four patients with primary hyperaldosteronism were treated with
nadroparin
> >>
> > 4100
> >
> >> or 6150 antiXa IU daily for 4 days. Plasma and urine sodium and
potassium,
> >>
> > and
> >
> >> plasma aldosterone and renin were monitored before, during and after
the
> >>
> > study.
> >
> >> After four days of treatment, and for the following two days, plasma
> >>
> > aldosterone
> >
> >> was decreased (by a mean of 49% on Day 6), and urinary Na/K was
increased
> >> (3.7-fold). The direction of the changes was reversed on Day 8. The
study
> >>
> > has
> >
> >> confirmed t_*he effect of low molecular weight heparin on aldosterone,
and
> >>
> > makes
> >
> >> it unlikely that it is related to inhibition of angiotensin II
stimulation
> >>
> > in
> >
> >> these patients, as renin could not be detected in their plasma.*_
> >>
> >> PMID: 1330575 [PubMed - indexed for MEDLINE]
> >>
> >> 4: Ter Arkh. 1985;57(6):78-81.
> >>
> >> [Hypotensive and diuretic effect of heparin in patients with
> >>
> > glomerulonephritis]
> >
> >> [Article in Russian]
> >>
> >> Kutyrina IM, Nikishova TA, Tareeva IE.
> >>
> >> The hypotensive and diuretic properties of heparin were evaluated in 95
> >>
> > patients
> >
> >> with different clinical and morphological varieties of chronic
> >> glomerulonephritis (CGN). The arterial blood pressure dropped in all
the
> >> patients treated with heparin. The maximal effect was attained toward
the
> >>
> > end of
> >
> >> heparin treatment (by the 35th-50th day). In patients with hypertonic
and
> >>
> > mixed
> >
> >> nephritis associated with renal failure, (the glomerular filtration
rate
> >>
> > under
> >
> >> 35 ml/min), the BP lowering induced by heparin was accompanied by the
> >> deterioration of renal function. The diuretic and natriuretic effects
were
> >> recorded in 81 out of the 95 patients. The maximal values of diuresis
and
> >>
> > sodium
> >
> >> excretion were detected on the 14th-16th day of the treatment during
the
> >>
> > use of
> >
> >> the maximal doses of heparin. It was established that heparin-induced
> >>
> > inhibition
> >
> >> of aldosterone synthesis plays the key role in the genesis of the
> >>
> > diuretic,
> >
> >> natriuretic and hypotensive action of the drug. It is concluded that
> >>
> > diuretic
> >
> >> and hypotensive properties of heparin can be made use of in the
treatment
> >>
> > of
> >
> >> nephrological patients.
> >>
> >> PMID: 4071420 [PubMed - indexed for MEDLINE]
> >>
> >> 5: Acta Med Scand. 1975 Jan-Feb;197(1-2):99-108.
> >>
> >> Inhibition of adrenal function in man by heparin or heparinoid Ro
1-8307.
> >>
> >> Kloppenborg PW, Casparie AF, Benraad TJ, Majoor CL.
> >>
> >> _*Heparin and the heparinoid Ro 1-8307 inhibited the secretory rate of
> >>
> > aldosterone
> >
> >> in physiological or pathological aldosteronism to the level found in
> >>
> > normal
> >
> >> subjects on liberal sodium intake. In addition, these compounds
inhibited
> >> corticosterone biosynthesis, although less markedly than that of
> >>
> > aldosterone.
> >
> >> Indications of interference with cortisol production have not been
found.
> >>
> > During
> >
> >> drug treatment angiotensin, in doses of 5-10 ng/kg b.wt./min, did not
> >>
> > stimulate
> >
> >> aldosterone secretion. ACTH responsiveness of the adrenals--indicated
by
> >>
> > the
> >
> >> fractional increases of both aldosterone and corticosterone secretory
> >> rates--remained unchanged. In two studies heparin had no consistent
effect
> >>
> > on
> >
> >> plasma renin activity.*_
> >>
> >> Publication Types:
> >>     Clinical Trial
> >>     Controlled Clinical Trial
> >>
> >> PMID: 47702 [PubMed - indexed for MEDLINE]
> >>
> >> 6: Metabolism. 1966 Jun;15(6):542-7.
> >>
> >> Mechanism of heparin inhibition of adrenal steroid A ring reduction.
> >>
> >> Troop RC, Krzanowski PT, Biggs JT Jr.
> >>
> >> PMID: 4379864 [PubMed - indexed for MEDLINE]
> >>
> >>
> >>
> >>
> >>
> >>
> >> _______________________________________________
> >> OpenHeart-L mailing list
> >>
> >> Send postings to:
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> >>
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> >>
> > and
> >
> >> disclaimers posted at:
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> >> -----------------------------------------
> >>
> >
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> >
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