Clinical Toxicology (2014), 52, 584–593 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 1556-3650 print / 1556-9519 online DOI: 10.3109/15563650.2014.923903

REVIEW ARTICLE

Barium toxicity and the role of the potassium inward rectifier current B. S. BHOELAN,1* C. H. STEVERING,1* A. T. J. VAN DER BOOG,1* and M. A. G. VAN DER HEYDEN2

Clinical Toxicology Downloaded from informahealthcare.com by The University of Manchester on 10/21/14 For personal use only.

1Participant 2Division

in the Honours Program CRU2006 Bachelor, University Medical Center Utrecht, Utrecht, The Netherlands of Heart and Lungs, Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands

Introduction. Barium is a stable divalent earth metal and highly toxic upon acute and chronic exposure. Barium is present in many products and involved in a number of industrial processes. Barium targets the potassium inward rectifier channels (IRCs) of the KCNJx gene family. Extracellular barium enters and strongly binds the potassium selectivity filter region resulting in blockade of the potassium conducting pore. IRCs are involved in numerous physiological processes of the human body and the most barium sensitive IRCs are highly expressed in all muscle types. Objective. Our purpose was correlate to the clinical outcome of acute barium poisoning in man to current knowledge on IRC function. Methodology. The primary literature search was performed using Medline, Scopus and Google Scholar using search terms “barium AND poisoning”; “barium AND intoxication”; “barium AND case report” and retrieved publications from 1945 through 2012. Additional case reports were retrieved based on the reference lists of the primary hits. Duplicate publications, or publications presenting identical cases were omitted. A total of 39 case reports on acute barium poisoning containing 226 human subjects were identified for review. Results. BaCO3 was the most frequent source and food the most frequent mode of poisoning. Patients suffered from gastrointestinal (vomiting, diarrhea), cardiovascular (arrhythmias, hypertension), neuromuscular (abnormal reflexes, paralysis), respiratory (respiratory arrest/failure) and metabolic (hypokalemia) symptoms. Severe hypokalemia (⬍ 2.5 mM) was observed from barium serum concentrations greater than or equal to 0.0025 mM. Review of the ECG outcomes demonstrated ventricular extrasystoles, ST changes and profound U-waves to be associated strongly with poisoning. Most common treatment modalities were gastric lavage, oral sulfates, potassium i.v. and cardiorespiratory support. 27 patients (12%) died from barium poisoning. Conclusions. Barium is a potent, non-specific inhibitor of the potassium IRC current and affects all types of muscle at micromolar concentrations. Gastrointestinal symptoms frequently occur early in the course of barium poisoning. Hypokalemia resulting from an intracellular shift of potassium and the direct effect of barium at the potassium channels explain the cardiac arrhythmias and muscle weakness which commonly occur in barium poisoning. Treatment of barium poisoning is mainly supportive. Orally administered sulfate salts to form insoluble barium sulfate in the intestinal tract and potassium supplementation have potential but unproven benefit. Keywords

ECG; IK1; Poisoning; Ion channel; Paralysis; Arrhythmia

Introduction

barium, in the manganese oxide containing mineral magnesia nigra. In 1784, William Withering described barium carbonate containing minerals, known as “terra ponderosa” later called “Witherite”, from the mines of Cumberland.2 First scientific descriptions of barium in humans appeared shortly later. In 1790, barium containing minerals (terra ponderosa muriata (BaCl2)) have been described in clinical practice to treat cancer, ulcers and dropsy (edema).3 Interestingly, Dr. Crawford herein stated that the preparation only works when made with distilled or pure water, but not with “hard” water. It is tempting to speculate that “hard” water, which at those times also meant water with a high mineral content, resulted in the formation of insoluble barium salts that could not be absorbed. Furthermore, he stated that the preparation could be used as a laxative, diaphoretic and sudorific. The years after, clinicians have applied this preparation in a number of different diseases, such as reported in 1792 for the successful treatment of Scrophula (an old name encompassing tuberculous cervical lymphadenitis associated

Barium is a stable earth metal with an atomic weight of 137.3 and is highly toxic. In its compounds it is a divalent positive ion. Water solubility of its chloride and nitrate salts is relatively high, whereas its carbonate and sulfate salts are rather water insoluble, but their solubility increases in an acid environment. Barium is present in many products, like rodenticides, insecticides, depilatories and fireworks, and has important roles in many industrial processes.1 In the second half of the 18th century, Carl Scheele announced the existence of a new substance, later named

Received 6 January 2014; accepted 6 May 2014. *These authors contributed equally. Address correspondence to Dr. Marcel A. G. van der Heyden, Division of Heart and Lungs, Department of Medical Physiology, Yalelaan 50, 3584 CM Utrecht, The Netherlands. Tel: ⫹ 31-30-2538901, Fax: ⫹ 31-302539064. E-mail: [email protected]

584

Clinical Toxicology Downloaded from informahealthcare.com by The University of Manchester on 10/21/14 For personal use only.

Barium poisoning symptoms like ulcers), and leprosy.4 Soon afterwards, barium salts were used in a plethora of conditions as exemplified by Hufelands book published in 1794 who strongly advocated its use.5 However, soon after the first clinical application of barium salts, a case report on the dramatic effects of overdosing, including muscle paralysis, was reported by Mather, a surgeon in York, in 1795.6 In the beginning of 19th century, it became apparent that barium salts had only to be given with great caution as they had a number of adverse effects as indicated by Schwilgué in 1812.7 It was well known in 1888 that barium increased vascular contraction and blood pressure, and an editorial in the Lancet reported Professor R. Kobert’s efforts, although unsuccessful, to treat dilated cutaneous veins by an ointment containing BaCl2.8 In the early 20th century, BaCl2 was used by some clinicians to treat heart block in Adams-Stokes seizures described by Cohn and Levine in 1925.9 When reviewing the contemporary literature, Gilchrist concluded in 1934 that “barium chloride does appear to have some effect in reducing the frequency of seizures”, although the subsequent cases described by the author himself did not support the previous data.10 Currently, the insoluble BaSO4 is used in daily clinical practice as a contrast agent in gastro-intestinal imaging. For a comprehensive review on the use of barium salts in medicine we refer the readers to Schott.11 While barium toxicity had been recognized 230 years ago, insights into at least a part of its etiology had to wait on the discovery of the potassium inward rectifier current in the late 1940s and cloning of the underlying ion channels in the early 1990s.12 Inward rectifier channels (IRCs), encoded by the KCNJx gene family are involved in numerous physiological processes of the human body.12 For example they determine resting membrane potential in excitable cells and final repolarization in cardiac myocytes, are involved in processes like insulin secretion, cardioprotection during ischemia and they have a role in heart rhythm regulation and renal solute and water homeostasis. The seventeen KCNJx genes are grouped into seven different subfamilies, coding for KIR1.x to KIR7.x channel proteins, and each gene has its own specific, but partially overlapping, expression pattern. A common feature of the IRCs is their sensitivity for barium ion-dependent blockade. The purpose of this review is to summarize the known clinical features of barium poisoning and correlate them with the actions of barium at IRCs. Baritosis, resulting from the inhalation of barium containing particles, will not be discussed in this paper since it is unclear to which extent a role of IRCs in the pathophysiology is involved. We refer readers to Doig and Seaton et al. for informative papers on baritosis.13,14

Methods We screened Medline, Scopus and Google Scholar databases using the search terms “barium AND poisoning”; “barium AND intoxication”; “barium AND case report” and retrieved publications from 1945 through 2012. Additional case reports were retrieved on basis of the reference lists of the Copyright © Informa Healthcare USA, Inc. 2014

585

primary hit papers. Duplicate publications or publications presenting identical cases were omitted. Reports written in the non-English languages were read as such by the reviewing authors (German, French) and/or translated with Google translator and subsequently discussed line by line and vis-àvis with native speakers (French, Japanese, Chinese) from the department of Medical Physiology.

Results A total of 39 case reports on acute barium poisoning containing 226 human subjects were identified for review (Table 1). Four papers presented large cases series whereas the majority of publications described only one case. Sources of barium resulting in poisoning cases Most cases of barium poisoning were due to sources of barium in everyday life products. Figure 1 provides a distribution of the events leading to the studied poisoning cases. There is a large variety in sources of barium poisoning (Table 2). The high frequency of barium carbonate and barium chloride associated cases is probably due to their wide application. For many case reports describe the accidental use of barium carbonate, which was a common rodenticide in the past, instead of flour. Currently, barium carbonate is less used as a rodenticide since more efficient poisons, such as anticoagulants, have been developed and barium carbonate based poisons have been taken from the market in many countries. Barium chloride finds wide application in the laboratory and accidental (mistaken for NaCl) or purposely (suicide attempt) intakes have been reported from the chemical industry, the chemistry classroom or the pharmacy. Barium nitrate and barium chlorate are both components of fireworks and explosives, while barium styphnate is primarily used in priming compositions of bullets and explosives, and as a rocket propellant. Barium poisoning in these cases was often the result of an explosion or accidents with fireworks, even consuming the latter. Shaving powder and depilatory agents containing barium sulfide were ingested in five cases of attempted suicide. Barium acetate and barium stearate are commonly used in industry, for example in plastic fabrication. A barium polysulfide with the tradename Neopol™ is an insecticide and fungicide, still being produced in China. Finally, barium sulfate in suspension is frequently used clinically as a contrast agent for diagnostic procedures. The absorption of the metal is limited by the low solubility of barium sulfate. However, overdoses of barium sulfate or certain pathophysiological conditions,15,16 such as stasis of contrast material, can still result in poisoning. Beside the poisoning cases indicated above, an act of homicidal barium chloride poisoning is described recently.17 On first sight a remarkable gender disparity can be observed since 185 of the investigated barium poisonings concerned males (81%). This largely skewed distribution between the sexes can be partly attributed to two case reports containing large groups of males: eighty-five soldiers and twenty-seven police personnel were victim of food poisoning due to flour

586

B. S. Bhoelan et al. Table 1. Overview of case-reports reviewed.

Clinical Toxicology Downloaded from informahealthcare.com by The University of Manchester on 10/21/14 For personal use only.

Case 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39

# subjects

Origin of paper

85 7 1 19 2 2 1 1 1 1 1 1 1 1 1 7 1 1 1 1 1 1 1 2 1 1 1 44 1 1 2 1 27 1 1 1 1 1 1

UK South-Africa UK Israel Israel Hungary US Denmark US US Australia US US Japan Germany US France India US New Zealand India France France US Italy/UK US Belgium Brazil Taiwan Sweden India India Bangladesh US India China/Taiwan France India Egypt

Remarks

References

Detailed description of 3 illustrative cases

18 64 68 69 65 70 71 72 73 20 74 75 21 22 76 23 77 78 79 80 81 16 15 82 83 24 84 85 25 26 86 87 19 88 89 90 27 28 91

Detailed description of 2 illustrative cases Paper in German language Includes literature review of 131 subjects

Includes literature review of ⬎ 100 subjects Paper in Japanese language Paper in French language

Paper in French language

based products containing barium carbonate.18,19 Omitting these groups shifted the distribution into 64% males. Clinical symptoms The symptoms that appeared after poisoning were fairly consistent among the different case reports. Table 3 provides

an overview of symptom prevalence. Most notable are vomiting, diarrhea, arrhythmias, effects on pulse rate, muscle weakness, absent or abnormal reflexes, paralysis, respiratory arrest/failure and hypokalemia. Two large clusters of acute barium poisoning, each occurred after a single food-based Table 2. Sources of barium associated with acute poisoning cases.

10.6%

1.8%

0.9% Contaminated contrast

3.1% 22.6%

Number of eventsa

Number of pts.

12 8 5 3 2 2

156 8 5 3 2 2

1 1 1 4

1 1 1 47

Food poisoning Accident Suicidal ingestion

61.1%

Source of barium

Iatrogenic Unknown

Fig. 1. Events leading to barium poisoning among the 39 studied case reports. Food poisoning and contaminated contrast agents were major causes of poisoning events involving large patients groups. Suicidal ingestion was a third major cause of poisoning (colour version of this figure can be found in the online version at www.informahealthcare.com/ctx).

Barium carbonate Barium chloride Barium sulfide Barium sulfate Barium nitrate Barium polysulfide (Neopol™) Barium acetate Barium chlorate Barium styphnate Unknown or mixtures aOne

event may involve multiple patients (e.g. food poisoning). Clinical Toxicology vol. 52 no. 6 2014

Barium poisoning Table 3. Clinical symptoms associated with acute barium poisoing. Affected system General conditions

Clinical Toxicology Downloaded from informahealthcare.com by The University of Manchester on 10/21/14 For personal use only.

Cardiovascular

Respiratory

Gastro-intestinal

Neuromuscular

Sensory Metabolic Others

Symptoms Dizziness Headache Coma Speech problems Weakness Sweating Feeling cold Vision problems Consciousness (reduced) Drowsiness Arrythmias Effects on pulse rate Hypertension Hypotension ECG abnormalities Effects on heart rate Collapsed Cardiovascular failure Respiratory arrest/failure Dyspnea Effects on respiration rate Respiratory muscle weakness Respiratory muscle paralysis Cyanosed Vomiting Diarrhea Abdominal pain Abdominal colic Gastroenteritis Nausea Absent or abnormal reflexes Paralysis Muscle weakness Dilated pupils Dysarthria Quadriparesis Convulsions Heaviness in limbs Tenesmus Tingling Paresthesia Sensory diminished Hypokalemia Acidose Abnormal temperature Speech problems Shock

No. affected pts. (%) (n ⫽ 226) 88 (38.9) 52 (23.0) 48 (21.2) 44 (19.5) 17 (7.5) 7 (3.1) 5 (2.2) 4 (1.8) 3 (1.3) 1 (0.4) 134 (59.3) 96 (42.5) 38 (16.8) 14 (6.2) 28 (4.9) 7 (3.1) 5 (2.2) 3 (1.3) 59 (26.1) 46 (20.4) 32 (14.2) 6 (2.7) 5 (2.2) 5 (2.2) 213 (94.2) 177 (78.3) 95 (42.0) 87 (38.5) 86 (38.1) 59 (26.1) 130 (57.5) 125 (55.3) 95 (42.0) 89 (39.4) 9 (4.0) 9 (4.0) 4 (1.8) 3 (1.3) 3 (1.3) 86 (38.1) 21 (9.3) 1 (0.4) 39 (17.3) 9 (3.9) 5 (2.2) 4 (1.8) 2 (0.9)

exposure. The 1945 report of Morton18 describes poisoning of eighty-five British soldiers due to two different types of barium carbonate contaminated pastry with barium concentrations as high as 15 g per average portion in marmalade tart, and lower concentrations in treacle tart. The general clinical picture of all patients was similar, but symptoms occurred earlier in the thirteen marmalade tart victims (45–90 min) than in the seventy-two treacle tart victims (120 min). Based on this large cohort, the author distinguished three separate stages: (1) an acute gastro-enteritis with mild sensory disturbance; (2) loss of deep reflexes and the onset of muscle paralysis; (3) progressive muscular paralysis. Treatment of the patients was purely symptomatic since the cause of Copyright © Informa Healthcare USA, Inc. 2014

587

illness was unknown. Treatment consisted of rest, warmth, emetic of salt and water, potassium permanganate solutions as a gastric astringent, magnesium sulfate and enemata. By the fourth to eight day all affected soldiers regained full power and there were no deaths. The second large cluster, presented in 2009, consisted of twenty-seven policemen experiencing barium poisoning after consuming fried vegetables coated with barium carbonate-contaminated flour during the Iftar meal that concludes a day of fasting during the Ramadan period.19 Abdominal pain and vomiting followed by diarrhea started 1 to 2 h after the meal. Subsequently patients developed cramps, pains and general paresthesia in the limbs. On hospital admission, twenty patients showed respiratory problems and different grades of muscle weakness with areflexia. At this time ECG abnormalities, i.e. flat ST segments and U-waves, were observed. Patients received potassium i.v. and fluid and oxygen supplementation. Sixteen hours following admission twelve patients had died due to respiratory failure. The authors suggest that the high death rate may be related to the 12-h food and fluid fasting period prior to the meal, which may have increased food intake and barium absorbance. Review of the complete set of cases indicated that clinical symptoms occurred in a similar sequence of events as presented by Morton.18 However the clinical picture was rapidly altering and varied in time between individual patients. Earliest symptoms, typically appear 45–90 min after oral ingestion, and include nausea, vomiting, diarrhea, abdominal pain, and paresthesia around the mouth and neck. Two to three hours after the onset of illness tingling transfers to the hands and feet area. Also the vomiting and diarrhea continues for the next 24 h. From that point onwards, symptoms become more neuromuscular, reflexes are abnormal and even absent later. Varying degrees of muscle paralysis develops, in which the extensor groups of muscles become affected before the flexor, the arms before the legs. Sensation is unaffected. The cardiovascular effects of barium also become noticeable. Both sinus bradycardia and tachycardia can be observed as well as hypotension and hypertension. In almost half of the cases cardiac arrhythmias or other ECG abnormalities are apparent. In the reviewed cases, U-waves, ventricular extrasystoles, and ST flattening were observed in approximately 77%, 28% and 21% of the cases respectively (Fig. 2). Unfortunately, a characteristic order of succession in the appearance of the different ECG changes cannot be extracted from our reviewed cases. Typically, hypokalemia occurs in many cases. Ten of our studied cases provided both plasma/serum barium and potassium concentrations.16,20–28 Normal potassium concentrations in human plasma are between 3.7 and 5.2 mM (mEq/l). As shown in Fig. 3, plasma/serum barium concentrations as low as 0.0025 mM were associated with hypokalemia. Interestingly, higher barium concentrations did not result in a further dose-dependent decrease in plasma potassium levels. Subsequently, muscle paralysis proceeds. General muscle paralysis starts on the second day of the illness and lasts for another 24 h. A part of the patients suffer from paralysis of the respiratory muscles, which results in dyspnea and in a

588

B. S. Bhoelan et al. Sinus rhythm Sinus tachycardia Sinus bradycardia Ventricular extrasystoles Ventricular tachycardia Torsades des pointes Atrial fibrillation Ventricular fibrillation AV block Right bundle branch block QRS widening ST changes Flattened T waves T wave inversion U waves 0

10

20

30 40 50 Percentage of patients

60

70

80

Fig. 2. Classification of ECG readouts in barium poisoning patients. The appearance of profound U-waves is a major electrical characteristic of poisoning.

quarter of the patients in respiratory arrest. In our reviewed cases, 27 patients (12%) died as a result of barium poisoning. When recovery occurs, it happens surprisingly rapidly and, in general, within a week all affected muscles regain their full power. IRCs and barium blockade The IRC family, which includes 7 subfamilies, is encoded by the KCNJ-genes (KIR1–7).29 The KIR protein consist of two transmembrane domains, a short pore loop that harbours the potassium selectivity filter and intracellularly located N⫺ and C-termini. Each of the subfamily gene products display their own characteristics, some having strong, and others weak rectifying potential, some responding to metabolic stimuli or neurotransmitters directly. Strong rectifying channels like KIR2.x, KIR3.x and KIR6.x Potassium in plasma (mM)

Clinical Toxicology Downloaded from informahealthcare.com by The University of Manchester on 10/21/14 For personal use only.

QT prolongation

5

Serum

4

Plasma

3 2 1 0 0.001

0.01 0.1 Barium in plasma/serum (mM)

1

Fig. 3. Barium-Potassium relationships in plasma/serum from patients suffering barium poisoning. Severe hypokalemia is associated with barium concentrations as low as 0.0025 mM. Beyond this concentration, no dose-response effect can be observed.

are mostly expressed in excitable tissues, e.g. cardiac, skeletal and smooth muscle and neurons, whereas weak rectifiers like KIR1.x, KIR4, KIR5 and KIR7 are expressed in various other tissue types and organs and have a role in processes like potassium homeostasis (kidney), and insulin release (pancreas).30 The barium ion is bivalent with an atomic radius of 222 pm which is close to that of K⫹ (227 pm). Based on these properties it will fit into the potassium selectivity filter, but by its larger charge it probably binds too strong resulting in block of K⫹ flow.31 Only supraphysiological concentrations of extracellular potassium (500 mM and more) will “push” barium ion through the channel to become cytoplasmic. Obviously, barium plasma concentrations will depend, apart from the dose, on the source, absorbance and clearance. Akai et al. reported on a patient who ingested 0.1 g of BaCl2 resulting in a barium plasma concentration of 8.5 μM.22 Cases of unknown amounts of BaCO3 or Ba(NO3)2 intake resulted in plasma concentrations of 2.723 and 6026 μM respectively. All KIR ion channels are sensitive to extracellular applied barium, but differences in IC50 values have been found between the several subfamily members. High sensitivity is found in members of the KIR2.x class (IC50 KIR2.1: 0.15–30 μM, KIR2.2: 6–40 μM, KIR2.3: 13 μM, KIR2.4: 15 μM), intermediate sensitivity in the KIR1 class (KIR1.1: 70 μM), KIR3 (KIR3.1:10–95 μM, KIR3.4: 92 μM), KIR4 (KIR4.1: 99 μM) and low sensitivity in KIR6 and KIR7 classes (KIR7.1: 1000 μM).12,32 Barium block involves a number of residues lining the outer vestibule, the potassium selectivity filter and the region of the selectivity filter facing the cytoplasm.33–36 Subfamily specific alterations in these residues explain differences in sensitivity. Highly sensitive IRCs have an Arg residue at the 125 position, Clinical Toxicology vol. 52 no. 6 2014

Barium poisoning

Clinical Toxicology Downloaded from informahealthcare.com by The University of Manchester on 10/21/14 For personal use only.

while the insensitive KIR7.1 has a Met residue. Replacing Met in KIR7.1 for Arg at the 125 position resulted in lowering IC50 to a range similar to sensitive IRCs.37,38 Experimental and animal data In dogs, Roza and Berman observed that following infusion of BaCl2 (1 μmol kg⫺ 1 min⫺ 1) the chronological order of ECG abnormalities were: premature supraventricular and ventricular contractions, multiple premature ventricular contractions, ventricular tachycardia and finally ventricular fibrillation and death.39 In the rat, BaCl2 (10 mg kg⫺ 1 min⫺ 1) infusion resulted in time, as stated by the author, in evidence of coronary spasms (sliding ST, T-wave inversion or increased T-height, PQ and QT lengthening), onset of bradycardia within thirty seconds, AV block, ventricular extrasystoles and ventricular fibrillation.40 In the experimental dog study mentioned above39 all animals responded with a rapid decrease in plasma potassium concentrations (0.3–2.1 mM as final concentrations). There was no clear relation between the total dose and the degree of potassium decrease which is in agreement with the summarized human data in Fig. 3. Potassium loss was not due to increased urine flow or potassium urine concentration, but erythrocyte potassium concentrations were found to be increased, mirroring the decreased plasma potassium concentrations. Redistribution of potassium from the extra- to the intracellular compartment, known as potassium shift, is thought to be due to barium dependent inhibition of potassium outward flow through the IRC in the context of a persistent active Na⫹/K⫹ exchanger activity (Fig. 4).39,41 Explaining barium poisoning symptoms; hypokalemia, direct IK1 blockade or both? Hypokalemia is known as an underlying cause of cardiac arrhythmias and muscle weakness.42–44 In hypokalemic paralysis patients, skeletal muscle cell resting membrane potential paradoxically depolarizes which renders sodium channels inactive which counteracts action potential formation. Impaired resting membrane potential stability in cardiac muscle, normally enforced by IRCs, results in hyperexcitability. The most striking ECG abnormality seen in the barium poisoning cases is the presence of a large U-wave. In experimental models, induction of hypokalemia results in U-wave amplitude increase.45,46 In a recent observational study 24% of patients with severe hypokalemia (serum potassium ⬍ 2.6 mM) presented prominent U-waves, followed in incidence by ventricular extrasystoles (21%) and ST segment depression (21%).47 Whereas the latter two symptoms are reported in barium poisoning cases (Fig. 2) with reasonable similar incidence (approximately 29% and 21% respectively), the incidence of prominent U-waves is approximately three-fold higher (77%). Therefore, it is reasonable to assume that apart from the barium induced hypokalemia, direct cardiac IK1 inhibition contributes significantly to the appearance and size of U-waves by prolonging the action potential. Copyright © Informa Healthcare USA, Inc. 2014

normal

K+

K+

589

3 Na+

2 K+

〔K+〕in=150 mM 〔K+〕out=5 mM barium

3 Na+

2 K+

〔K+〕in=153 mM 〔K+〕out=2 mM

Fig. 4. Proposed origin of hypokalemia resulting from barium poisoning. Normally, potassium outflow through IRCs along its concentration gradient is balanced by the sodium-potassium transporter. Upon barium poisoning, potassium outflow through IRC is inhibited while the sodium-potassium transporter remains active. Intracellular potassium concentrations ([K⫹]in) rise at the expense of extracellular potassium concentrations ([K⫹]out).

Andersen-Tawil Syndrome, a rare genetic disorder with a loss-of-function mutation in the KIR2.1 protein, gives intriguing insights into the potassium channel. Andersen-Tawil syndrome 1 produces large U-waves which are out of proportion to the near normal potassium concentrations,48 which support our view on the U-wave origin in barium poisoning. Furthermore, in a tissue model of Andersen-Tawil syndrome, Morita et al. demonstrated an increased incidence of U-wave appearance under conditions of hypokalemia.49 Finally, in rats barium was found to accumulate in cardiac tissue to a greater extent than other tissues, probably to the prominent expression of KIR2.x channels in cardiomyocytes,50 and by this characteristic barium may relatively enhance its effect on direct IK1 blocking effects as compared to the global hypokalemia that contributes to the symptoms in the heart. The relative contribution of barium associated hypokalemia and direct IK1 block to skeletal muscle weakness and paralysis is less clear. Andersen-Tawil Syndrome patients present episodic paralysis also, which in the majority of cases (55%) is associated with hypokalemia, but potassium levels are normal (10%) or even increased (22%) in

Clinical Toxicology Downloaded from informahealthcare.com by The University of Manchester on 10/21/14 For personal use only.

590

B. S. Bhoelan et al.

other cases.51 Therefore it is likely that the symptoms due to loss of IK1 density may be aggravated by hypokalemia with respect to skeletal muscle function in many, but not all, cases. In Andersen-Tawil Syndrome patients, therapeutic or prophylactic oral potassium was often, but not always, effective to suppress paralysis episodes.52 In comparison to cardiac and skeletal myocytes, less is known with respect to IRC expression and function in smooth muscle cells.53 KIR2.1 channels are being expressed in arterial vascular smooth muscle cells and have been implicated in vascular dilation.54,55 Therefore, the observed hypo- and hypertension resulting from barium poisoning may well be related to IRC function in vascular smooth muscle. However, deciphering the underlying mechanisms into detail awaits further research. The same accounts for the gastrointestinal symptoms associated with barium poisoning (vomiting, diarrhea). Again it is tempting to speculate that these may be due to impaired IRC functioning in smooth muscle cells lining the gastrointestinal tract. Only a few studies demonstrate the expression of IRC channel proteins and/or function of various subtypes in smooth muscle cells from the gastrointestinal tract. Murine KIR6.2 mRNA was found in colonic smooth muscle cells, whereas no KIR6.1 expression was found.56 Canine KIR2.1, KIR3.1 and KIR3.2, but not KIR2.2, KIR2.3, KIR3.3 and KIR3.4, mRNA expression was found in circular muscle cells from colon, duodenum, jejunum and ileum.57,58 Mucosal cells may also be involved in the gastrointestinal response to barium poisoning. For

example, KCNJ15 is strongly expressed in rabbit and mouse gastric mucosal cells and the resulting channels are involved in acid secretion.59 Finally, it is important to notice that the presented gastro-intestinal findings here are common after ingestion of a wide variety of metal salts. Therefore, tremendous amounts of work have to be performed to functionally link symptoms to defined IRC dysfunction. Currently it is unknown whether all clinical symptoms of barium poisoning can be primarily attributed to IRC blockade. Especially at higher concentrations, barium may induce toxic effects via additional, currently unknown, targets. Treatment Because of the urgent character of the symptoms and the fact that in a vast majority of the cases the cause of illness at presentation is not clear, treatment of acute barium poisoning in the reviewed cases was based on a symptomatic approach. This explains the broad spectrum of treatment modalities shown in Fig. 5. In cases in which barium poisoning is evident or suspected, treatment aimed at reducing absorption and increasing barium excretion was indicated. Barium excretion is mainly by feces (90%), and only 2–7% by the urine.60,61 Total excretion in 14 days after exposure is between 77 and 91%.61 In general, main treatment modalities were rehydration, gastric lavage with or without sodium or magnesium sulfate, potassium supplementation and cardiorespiratory support. The procedure of gastric lavage

Rehydration oral Rehydration i.v. Gastric lavage Sulphate oral Diuretics Dialysis Enema Epsam salt Castor oil Potassium i.v. Potassium oral Correct electrolyte imbalances Glucose i.v. Anti-arhythmics Magnesium sulphate i.v. Cardiorespiratory support Blood transfusion Morphine Calcium Adrenaline Dopamine Sedatives Nikethamide Lypressine Hot drinks Brandy Warmth No treatment Treatment unknown

Recovery Death Unknown

0

10

20

30

40

50 60 70 80 Number of patients

90

100

110

120

Fig. 5. Frequencies of used treatment modalities used among the 226 patients. Most patients received multiple interventions. Colours within the bars depict the clinical outcome (colour version of this figure can be found in the online version at www.informahealthcare.com/ctx). Clinical Toxicology vol. 52 no. 6 2014

Clinical Toxicology Downloaded from informahealthcare.com by The University of Manchester on 10/21/14 For personal use only.

Barium poisoning following poisoning has largely fallen out of favor since the publication of the 1997 position paper on this subject.62,63 To prevent further uptake of the poisonous substance in the gastro-intestinal tract gastric lavage but also enema has been applied. In a number of cases, gastric lavage was combined with sodium or magnesium sulfate in order to form insoluble barium sulfate that cannot be absorbed through gastro-intestinal mucosa. From Fig. 5, it appears that enema was an often applied treatment modality, but numbers are biased due to the fact that enema was used in a case involving eighty-five soldiers.18 The same accounts for warmth and hot drinks. Laxatives such as castor oil and epsam salts were applied in two cases.18,64 Diuretics and dialysis have also been used to increase barium clearance. Rehydration is supposedly used to address the fluid depletion caused by vomiting that involves acute barium poisoning. The most imposing sign in barium poisoning is hypokalemia and therefore potassium supplementation was indicated. In the studied cases, potassium was administered both oral and i.v. but in such cases patients should be monitored closely to prevent rebound hyperkalemia resulting from backward shift of cellular potassium once direct channel block is relieved. Cardiac dysrhythmia has been treated with anti-arrhythmic drugs and magnesium sulfate. In the more critical cases,19,23,26 in which the respiratory and heart muscle function was severely impaired, cardiorespiratory support was indicated, but unfortunately not all patients could be saved by this intervention. Besides potassium, depletion of other electrolytes occurred also. This was addressed by supplementation of the concerning electrolytes. In three cases glucose was given,26,64,65 most likely indicated by the observed hypoglycaemia. Finally, the remaining treatment modalities, e.g. morphine, blood transfusion, nikethamide, were used because of additional pathologies that were barium poisoning unrelated. The majority of patients recovered without long term effects. Unfortunately, in 12% of the cases, barium poisoning was fatal. Most frequently occurring causes of death were respiratory failure due to respiratory muscles paralysis and cardiac arrhythmias. Chronic barium poisoning Chronic barium poisoning has been reported less frequently and is mostly occupation related. One detailed study was published by Meng and coworkers.66 The authors described forty people working in the plastic industry that suffered from chronic barium stearate poisoning. Exposure time to barium stearate was between 4 and 12 months. First symptoms became apparent between 5 and 20 days. Symptoms were largely similar to those in acute poisoning cases. All victims displayed hypokalemia, average serum potassium concentrations were 2.3 ⫾ 0.6 mM. All patients showed muscle weakness, but to different degrees, thirty-two patients suffered from neurological symptoms, like amnesia, dizziness, insomnia and speech problems. Two patients experienced respiratory muscle weakness. ECG analysis showed enlarged U-waves in 39 patients, premature ventricular contractions Copyright © Informa Healthcare USA, Inc. 2014

591

in 10, tachycardia in 8, bradycardia in 5, atrial fibrillation in 3, AV block in 4, and ST-changes in 10 patients. Cranial CT scans of 39 patients showed no lesions and none of the patients experienced thyroid gland abnormalities. Wang and Li described two male cases of chronic barium stearate poisoning.67 Victims were exposed for 30 days and suffered from muscle weakness, extreme hypokalemia (1.48 and 1.22 mM), sinus arrhythmia, displayed T-wave flattening and large U-waves. Both patients were treated with potassium supplementation for 7 and 8 days and were fully recovered and discharged after 10 and 12 days of hospitalization, respectively.

Conclusions Acute barium poisoning cases were mostly related to food poisoning with rodenticides and contaminated contrast agents in the past, but due to replacement, improved regulations and control on these substances, suicidal ingesting may become a more prevalent factor in poisoning cases. Most symptoms point to involvement of cardiac and skeletal muscle, either by direct IRC blockade or indirectly by hypokalemia. Gastrointestinal symptoms are to date mainly unexplained. The most apparent ECG abnormality was the presence of profound U-waves that can be explained by a combination of direct IRC blockade and hypokalemia. Treatment modalities were targeted at prevention of further intoxication by means of gastric lavage and oral sodium sulfate application. Furthermore, treatment was mainly based on a symptomatic approach involving potassium supplementation and cardiorespiratory support. Chronic barium poisoning showed a similar pattern of symptoms.

Acknowledgements We thank Hiroki Takanari, Yuan Ji and Alexandre Bossu for assistance in interpreting Japanese, Chinese and French language case reports respectively.

Declaration of interest The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

References 1. Oskarsson A, Reeves AL. Barium. In: Nordberg G, Nordberg M, Fowler B, Friberg L, eds. Handbook of the Toxicology of Metals. Boston: Academic Press, 2007:407–414. 2. Withering W. Experiments and observations on the Terra Ponderosa, etc. Philos Trans R Soc Lond 1784; 74:293–311. 3. Crawford A. Medical Commentaries. 1790; 4:433–436. 4. Clark J. Account of the good effects derived from the Terra ponderosa muriata, in a peculiar species of Scrophula, occurring among negrous in the West-Indies. Medical Commentaries 1792; 6:267–270. 5. Hufeland CW. Vollständige Darstellung der medicinischen Kräfte und des Gebrauchs der salzsauren Schwererde. Berlin: Rottman; 1794. 6. Mather A. An account of the effects of an over-dose of the Terra Ponderosa Muriata. Medical Commentaries 1795; 9:265–270.

Clinical Toxicology Downloaded from informahealthcare.com by The University of Manchester on 10/21/14 For personal use only.

592

B. S. Bhoelan et al.

7. Schwilgué CJA. Traité de Matière Médicale. 2nd ed. Paris: Brosson 1809–1812; 1:407–410. 8. Anonymous. Similarity of barium to digitalis. Lancet 1888; 131: 1311–1312. 9. Cohn AE, Levine SA. The beneficial effects of barium chlorid on Adams-Stokes disease. Report of three cases. Arch Int Med 1925; 36:1–2. 10. Gilchrist AR. Ephedrine sulphate and barium chloride in the prevention of Stokes- Adams seizures. Br Med J 1934; 1:610–613. 11. Schott GD. Some observations on the history of the use of barium salts in medicine. Med Hist 1974; 18:9–21. 12. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 2010; 90:291–366. 13. Doig AT. Baritosis: a benign pneumoconiosis. Thorax 1976; 31: 30–39. 14. Seaton A, Ruckley VA, Addison J, Brown WR. Silicosis in barium miners. Thorax 1986; 41:591–595. 15. Pélissier-Alicot A, Léonetti G, Champsaur P, Allain P, Mauras Y, Botta A. Fatal poisoning due to intravasation after oral administration of barium sulfate for contrast radiography. Forensic Sci Int 1999; 106:109–113. 16. Savry C, Bouche O, Lefrant JY, Saissy G, Allain P. Barium sulfate poisoning? Ann Fr Anesth Reanim 1999; 18:454–457. 17. Ananda S, Shaohua Z, Liang L. Fatal barium chloride poisoning: four cases report and literature review. Am J Forensic Med Pathol 2013; 34:115–118. 18. Morton W. Poisoning by barium carbonate. Lancet 1945; 246: 738–739. 19. Ghose A, Sayeed AA, Hossain A, Rahman R, Faiz A, Haque G. Mass barium carbonate poisoning with fatal outcome, lessons learned: a case series. Cases J 2009; 2:9327. 20. Stewart DW, Hummel RP. Acute poisoning by a barium chloride burn. J Trauma 1984; 24:768–770. 21. Shankle R, Keane JR. Acute paralysis from inhaled barium carbonate. Arch Neurol 1988; 45:579–580. 22. Akai Y, Tabei K, Amemiya M, Sakairi Y, Kusano E, Asano Y, Nakayama T. A case of barium chloride poisoning. Nihon Kyukyu Igakukai Zasshi 1990; 16:34–37. 23. Johnsen CH, VanTassell VJ. Acute barium poisoning with respiratory failure and rhabdomyolysis. Ann Emerg Med 1991; 20:1138–1142. 24. Jacobs IA, Taddeo J, Kelly K, Valenziano C. Poisoning as a result of barium styphnate explosion. Am J Ind Med 2002; 41:285–288. 25. Hung Y, Chung H. Acute self-poisoning by ingestion of cadmium and barium. Nephrol Dial Transplant 2004; 19:1308–1309. 26. Bahlmann H, Lindwall R, Persson H. Acute barium nitrate intoxication treated by hemodialysis. Acta Anaesth Scand 2005; 49:110–112. 27. Payen C, Dellinger A, Pulce C, Cirimele V, Carbonnel V, Kintz P, Descotes J. Intoxication by large amounts of barium nitrate overcome by early massive K supplementation and oral administration of magnesium sulphate. Hum Exp Toxicol 2011; 30:34–37. 28. Deepthiraju B, Varma PRK. Barium toxicity a rare presentation of fireworks ingestion. Indian Pediatr 2012; 49:762. 29. Sánchez-Chapula JA, Van der Heyden MAG. Molecular regulation of cardiac inward rectifier potassium channels by pharmacologic agents. In: Zipes DP, Jalife J, eds. Cardiac electrophysiology from cell to bedside. Philadelphia: Elsevier Saunders; 2014:129–137. 30. De Boer TP, Houtman MJ, Compier M, Van der Heyden MAG. The mammalian KIR2.x inward rectifier ion channel family: expression pattern and pathophysiology. Acta Physiol (Oxf) 2010; 199:243–256. 31. Clarke OB, Caputo AT, Hill AP, Vandenberg JI, Smith BJ, Gulbis JM. Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels. Cell 2010; 141:1018–1029. 32. Coetzee WA, Amarillo Y, Chiu J, Chow A, Lau D, McCormack T, et al. Molecular diversity of K⫹ channels. Ann N Y Acad Sci 1999; 868:233–285. 33. Shieh RC, Chang JC, Arreola J. Interaction of Ba2 ⫹ with the pores of the cloned inward rectifier K⫹ channels Kir2.1 expressed in Xenopus oocytes. Biophys J 1998; 75:2313–2322.

34. Lancaster MK, Dibb KM, Quinn CC, Leach R, Lee JK, Findlay JBC, Boyett MR. Residues and mechanisms for slow activation and Ba2⫹ block of the cardiac muscarinic K⫹ channel, Kir3.1/Kir3.4. J Biol Chem 2000; 275:35831–35839. 35. Murata Y, Fujiwara Y, Kubo Y. Identification of a site involved in the block by extracellular Mg2⫹ and Ba2⫹ as well as permeation of K⫹ in the Kir2.1 K⫹ channel. J Physiol 2002; 544.3:665–677. 36. Lee YM, Thompson GA, Ashmole I, Leyland M, So I, Stanfield PR. Multiple residues in the P-region and M2 of murine Kir2.1 regulate blockage by external Ba2⫹. Korean J Physiol Pharmacol 2009; 13:61–70. 37. Krapivinsky G, Medina I, Eng L, Krapivinsky L, Yang Y, Clapham DE. A novel inward rectifier K⫹ channel with unique pore properties. Neuron 1998; 20:995–1005. 38. Döring F, Derst C, Wischmeyer E, Karschin C, Schneggenburger R, Daut J, Karschin A. The epithelial inward rectifier channel Kir7.1 displays unusual K⫹ permeation properties. J Neurosci 1998; 18: 8625–8636. 39. Roza O, Berman LB. The pathophysiology of barium: hypokalemic and cardiovascular effects. J Pharmacol Exp Ther 1971; 177: 433–439. 40. Marmo E. Effects of different drugs with beta-adrenolytic activity on experimental models of arrhythmias. Naunyn Schmiedebergs Arch Pharmakol 1971; 269:231–247. 41. Sperelakis N, Schneider MF, Harris, EJ. Decreased K⫹ conductance produced by Ba⫹⫹ in frog sartorius fibers. J Gen Physiol 1967; 50:1565–1583. 42. Ahlawat SK, Sachdev A. Hypokalaemic paralysis. Postgrad Med J 1999; 75:193–197. 43. Diercks DB, Shumaik GM, Harrigan RA, Bradley WJ, Chan TC. Electrocardiographic manifestations: electrolyte abnormalities. J Emerg Med 2004; 27:153–160. 44. El-Sherif N, Turitto G. Electrolyte disorders and arrhythmogenesis. Cardiol J 2011; 18:233–245. 45. Watanabe Y. Purkinje repolarization as a possible cause of the U wave in the electrocardiogram. Circulation 1975; 51:1030–1037. 46. Tai Fu L, Kato N, Takahashi N. Hypopotassemia-induced U wave in electrocardiogram (an experimental study for possible mechanism). Basic Res Cardiol 1984; 79:494–502. 47. Marti G, Schwarz C, Leichtle AB, Fiedler GM, Arampatzis S, Exadaktylos AK, Lindner G. Etiology and symptoms of severe hypokalemia in emergency department patients. Eur J Emerg Med 2014; 21:46–51. 48. Postema PG, Ritsema van Eck HJ, Opthof T, van Herpen G, van Dessel PF, Priori SG, et al. IK1 modulates the U-wave: insights in a 100-year-old enigma. Heart Rhythm 2009; 6:393–400. 49. Morita H, Zipes DP, Morita ST, Wu J. Mechanism of U wave and polymorphic ventricular tachycardia in a canine tissue model of Andersen-Tawil syndrome. Cardiovasc Res 2007; 75:510–518. 50. McCauley PT, Washington IS. Barium bioavailability as the chloride, sulfate, or carbonate salt in the rat. Drug Chem Toxicol 1983; 6:209–217. 51. Tristani-Firouzi M, Jensen JL, Donaldson MR, Sansone V, Meola G, Hahn A, et al. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest 2002; 110:381–388. 52. Canún S, Pérez N, Beirana LG. Andersen syndrome autosomal dominant in three generations. Am J Med Genet 1999; 85:147–156. 53. Thorneloe KS, Nelson MT. Ion channels in smooth muscle: regulators of intracellular calcium and contractility. Can J Physiol Pharmacol 2005; 83:215–242. 54. Bradley KK, Jaggar JH, Bonev AD, Heppner TJ, Flynn ER, Nelson MT, Horowitz B. Kir2.1 encodes the inward rectifier potassium channel in rat arterial smooth muscle cells. J Physiol 1999; 515:639–651. 55. Zaritsky JJ, Eckman DM, Wellman GC, Nelson MT, Schwarz TL. Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K⫹ current in K⫹-mediated vasodilation. Circ Res 2000; 87:160–166. Clinical Toxicology vol. 52 no. 6 2014

Clinical Toxicology Downloaded from informahealthcare.com by The University of Manchester on 10/21/14 For personal use only.

Barium poisoning 56. Koh SD, Bradley KK, Rae MG, Keef KD, Horowitz B, Sanders KM. Basal activation of ATP-sensitive potassium channels in murine colonic smooth muscle cell. Biophys J 1998; 75:1793–1800. 57. Flynn ER, McManus CA, Bradley KK, Koh SD, Hegarty TM, Horowitz B, Sanders KM. Inward rectifier potassium conductance regulates membrane potential of canine colonic smooth muscle. J Physiol 1999; 518:247–256. 58. Bradley KK, Hatton WJ, Mason HS, Walker RL, Flynn ER, Kenyon JL, Horowitz B. Kir3.1/3.2 encodes an IKACh-like current in gastrointestinal myocytes. Am J Physiol Gastrointest Liver Physiol 2000; 278:G289–G296. 59. He W, Liu W, Chew CS, Baker SS, Baker RD, Forte JG, Zhu L. Acid secretion- associated translocation of KCNJ15 in gastric parietal cells. Am J Physiol Gastrointest Liver Physiol 2011; 301: G591–G600. 60. Schroeder HA, Tipton IH, Nason AP. Trace metals in man: strontium and barium. J Chronic Dis 1972; 25:491–517. 61. Newton D, Harrison GE, Kang C, Warner AJ. Metabolism of injected barium in six healthy men. Health Phys 1991; 61:191–201. 62. Vale JA. Position statement: gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35:711–719. 63. Benson BE, Hoppu K, Troutman WG, Bedry R, Erdman A, Höjer J; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila). 2013; 51:140–146. 64. Dean G. Seven cases of barium carbonate poisoning. Br Med J 1950; 2:817–818. 65. Diengott D, Rozsa O, Levy N, Muammark S. Hypokalemia in barium poisoning. Lancet 1964; 284:343–344. 66. Meng SJ, Lu QL, Max ZX. Clinical analysis of chronic barium poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2009; 27:370–371. 67. Wang CZ, Li BD. Two cases of hypokalemic paralysis caused by chronic barium poisoning. Clin Focus 2007; 22:1369. 68. Jolleys A. Death following a barium enema in a child with hirschsprung’s disease. Br Med J 1952; 1:692–693. 69. Lewi Z, Bar-Khayim Y. Food-poisoning from barium carbonate. Lancet 1964; 284:342–343. 70. Jobba G, Rengei B. Über die Neopol-Vergiftung. Arch Toxicol 1971; 27:106–110. 71. Gould DB, Sorrell MR, Lupariello AD. Barium sulfide poisoning. Some factors contributing to survival. Arch Intern Med 1973; 132:891–894. 72. Berning J. Hypokalemia of barium poisoning. Lancet 1975; 305:110. 73. Wetherill SF, Guarino MJ, Cox RW. Acute renal failure associated with barium chloride poisoning. Ann Intern Med 1981; 95:187–188.

Copyright © Informa Healthcare USA, Inc. 2014

593

74. Phelan DM, Hagley SR, Guerin MD. Is hypokalaemia the cause of paralysis in barium poisoning? Br Med J 1984; 289:882. 75. Tenenbein M. Severe cardiac dysrhythmia from barium acetate ingestion. Pediatr Emerg Care 1985; 1:34–36. 76. Schorn TF, Olbricht C, Schüler A, Franz A, Wittek K, Balks HJ, et al. Barium carbonate intoxication. Intensive Care Med. 1991; 17:60–62. 77. Fogliani J, Giraud E, Henriquet D, Maitrasse B. Intoxication volontaire par le baryum. Ann Fr Anesth Réanim 1993; 12:508–511. 78. Gupta S. Barium carbonate, hypokalaemic paralysis and trismus. Postgrad Med J 1994; 70:938–939. 79. Downs JC, Millig D, Nichols CA. Suicidal ingestion of barium-sulfide containing shaving powder. Am J Forensic Med Pathol 1995; 16: 56–61. 80. Thomas M, Bowie D, Walker R. Acute barium intoxication following ingestion of ceramic glaze. Postgrad Med J 1998; 74:545–546. 81. Kakar A, Anand I, Sethi PK. Barium carbonate intoxication: an electrophysiological study. J Neurol Neurosurg Psychiatr 1998; 64:606–607. 82. Sigue G, Gamble L, Pelitere M, Venugopal S, Arcement L, Tahseen Rab S, Thakur V. From profound hypokalemia to life-threatening hyperkalemia: a case of barium sulfide poisoning. Arch Int Med 2000; 160:548–551. 83. Jourdan S, Bertoni M, Pellegrino S, Petrarulo M, Rossi M. Suicidal poisoning with barium chloride. Forensic Sci Int 2001; 119:263–265. 84. Koch M, Appoloni O, Haufroid V, Vincent J, Lheureux P. Acute barium intoxication and hemodiafiltration. J Toxicol 2003; 41: 363–367. 85. CDC (Centers for Disease Control and Prevention). Barium toxicity after exposure to contaminated contrast solution–Goias State, Brazil, 2003. MMWR Morb Mortal Wkly Rep 2003; 52:1047–1048. 86. Talwar V, Mehndiratta N, Verma PK. Barium poisoning mimicking Guillain-Barre syndrome. J Assoc Physicians India 2007; 50: 658–660. 87. Chaudhary SC, Aggarwal A, Avasthi R. Acute severe poisoning by barium carbonate (Rat Poison). J Indian Acad Clin Med 2008; 9:133–135. 88. Rhyee SH, Heard K. Acute barium toxicity from ingestion of “snake” fireworks. J Med Toxicol 2009; 5:209–213. 89. Torka P, Sharma R, Sood R. Rodenticide poisoning as a cause of quadriparesis: a rare entity. Am J Emerg Med 2009; 27:625.e1–e3. 90. Tsai CY, Tseng CC, Liu SF, Lin MC, Fang WF. Acute barium intoxication following accidental inhalation of barium chloride. Intern Med J 2011; 41:293–295. 91. El Masry MK, Abdelhamid WG, Abdeklader SI, Elmorsi SA, Abdelaziz SA. Massive and sustain K therapy saves life in barium chloride intoxication: A case report. IJCRI 2012; 3:35–38.

Barium toxicity and the role of the potassium inward rectifier current.

Barium is a stable divalent earth metal and highly toxic upon acute and chronic exposure. Barium is present in many products and involved in a number ...
270KB Sizes 6 Downloads 3 Views