Hypermagnesemia* A Potential Complication Theophyfline Intoxication Charcoal Charles’ During Treatment with Oral Activated and Magnesium-Containing A. Weber, It!. D. t and Rafael Al. of Cathartics Santiago, M. D. Toxic reaction to theophylline compounds is common. Oral activated charcoal (OAC) is a widely accepted mode of therapy for management of moderate to severe cases of theophylline toxicity. Magnesium-containing cathartics are generally recommended in conjunction with OAC in the treatment of drug or toxin ingestions. We report two cases of hypermagnesemia complicating the treatment of theo- , F. C. C. P phylline patients, toxicity with OAC and magnesium citrate. In both the hypermagnesemia contributed significantly to morbidity or mortality. In light of these cases and after review of the literature, we suggest that sorbitol be considered the cathartic agent of choice in the treatment of theophylline toxicity with OAC. (Chest 1989; 95:56-59) = oral OAC activated charcoal MAT multifocal atrial tachy- cardia T heophvlliiie toxicity remains a common occurrence recently been . clearance rate fully utilized of several drugs and in the management Oral shown intoxicated work n”2 by adsorbing gastrointestinal absorption.3 Activated the charcoal remaining a concentration gradient agent along generally recommended decrease the through adsorbed gradient with . transit time of the charcoal theoretically activated common efficacy use, as of theophylline it A 61-year is charcoal toxicity unaware applies or of their for treatment to the April bated Hall USAF Medical Center admitted in which tachycardia arrival in the tube, also given pam, 1edicine, Texas. tFellov; Staff, Pulmonary and Wilford Pulmonary Pulmonary Hall Critical USAF Care Division, During Medical Center, Disease Service. Disease Service, and Medicine, Uniformed Services University The opinions expressed are those of necessarily represent official USAF plicy. Manuscript Reprint Texas received requests: March Dr 24; Santiago, revision [TSAF Lackland Assistant Professor of AFB, artery occlusion sq and of the Health Sciences. the authors and do not accepted Hospital, 78236-5.300 56 Downloaded From: http://publications.chestnet.org/ on 09/09/2014 May 23. Lackland AFB, fell therapy pressure of2O blood rate and mm level artery was found to be 6.9 serum creatinine was 0.6 after admission. The patient well as six enterally, for a total of 55 g of magnesium pressure remained low various left vasopressor ventricle with agents. with diffuse relative An 1.8 Hg, IJmin! dynes’s associated admission, however, had was pulmonary Initial BUN 2 g of of magnesium over an 8-h echocardiogram revealed A Hypermagnesemia head citrate period. while CT (Webe a was oliguria received bradycardia hypokinesis. catheter after mg/dl; doses charcoal! dopamine of mm mg/dl. soon as the of 2,431 hours and IV index 90/60 Several Serum hemoperfusion mean index occurred sulfate after IV diaze- (PA) Hg, cardiac 6 mg/dl, magnesium Soon and mm Hg, pressure was were requiring resistance of 80 beats/mm. magnesium each sulfate control. anticonvulsants of 31/25 vascular citrate, MAT for for 30 g via a required phenobarbital A pulmonary a PA pressure a systemic a sinus and magne- Treatment of IV magnesium ensued, hypoafter serum charcoal, to 24. 1 p.g/ml, with was of multifocal g) of magnesium hypotension p.gfkg/min. Systemic with serum of 30 at revealing m, and mixture, initial which a intu- Shortly mg/dl). activated on an admission The (8.7 was patient reported developed, quickly She beat/mm. hypomagnesemia epilepticus levels 150 with ml diphenylhydantoin, theophylline following 1.8 to 2.4 1-g boluses of status placed Department 150 because admission, of p.g/ml. begun 2 h. Two Center arrest findings laboratory (normal, was and every the of 42.4 mg/dl 1.5 toxicity repeated at a rate EGG On Medical The and 3- captopril. activity. ventilation. and inhaled and Hall seizure pulse ICU, level was nasogastric mcm’. the *From or outpatient therapy, daily, a respiratory irregular (MAT) Her oxygen twice at Wilford mechanical theophylline level Room medical was deferred. of ca- of hypertension disease. of generalized a rapid, atrial orally experienced received theophylline to Wilford treatment she a history home mg Emergency with had pulmonary ofcontinuous period and support recently magnesium REPORTS woman 300 1987, questionable sium pro- white TheoDur arrival 10 and hypermagnesemia, to the morbidity involved. obstructive magnesium ducing hypermagnesemia. We present two cases patients consisted agonists, serum of any data on to the treatment potential old chronic tensive agents, magnesium citrate are commonly used in the of drug toxicities. Despite we are specifically of the CASE severe the OAC 1 the lumen of the to charcoal the use of a activated agents with in iatrogenic significantly to systemic of thefrom toxicity resulted contributed mortality the gut, prevent reabsorption of charcoaldrug, and help maintain a concentration across the gut wall that favors further drug excretion. Among cathartic and magnesium sulfate management of a variety their their the These thartics which CASE within further movement intestinal mucosal circulation into the gut.4 Since the binding of theophylline within the gut is potentially reversible,5 cathartic appears drug , down theophylline has the has been successof theophylline- (CI) tract preventing and by promoting the ophylline clinical activated charcoal (OAC) to enhance significantly Blood receiving a dilated scan was Santiago) unremarkable. Intravenous apparent creatinine on 4 of magnesium level level and to Following variables. The cardiac CASE 24 36 index lowering improved changes h patient the During ranged remains hospitalized first from 1 .8 to magnesium to values of 2.9 other six was the serum of a serum magnesium ofthe index the serum agents. cardiac and cognitive to the with performed lower the significant patient to moderate next the without to without lov; was attempt vasopressor dialysis normal, m mild all of hospitalization, m. Hemodialysis an the from were remained hemodialysis, over weaned Limin!sq was Following decreased, days in boluses output of < 10 ml!min. level. LJsq chloride Urine hospitalization successfully 2.2 benefit. clearance day four calcium hemodynamic to 3.6 later A 77-year admitted Medical old woman with to the Medical Center prolonged on 29 May hospital congestive Eventually course day serum cellulitus, was extubated and 52, theophylline level charcoal 300-ml dose of magnesium patient was blood pressure found dopamine and trates on chest Laboratory 3.1 mm, glucose, 304 7.8 mg/dl albumin, 1.6 magnesium BUN, g/dl. of 2.0 Llmin, mg/dl, occlusion with broad-spectrum namic response to patients the hemodynamic pursued. The theophylline diffuse cultures grew and died within An autopsy alveolar dopamine patient was Blood recognized, no study of revealed damage, Staphylococcus h and hemody- to this was not recognition evidence of of charcoal tubular by hypoactive sepsis, course. in the the myocardial made the failure,9 bowel and bradycardia, paralysis CN S depression, muscle with secondary respiratory kidneys are responsible homeostasis. Seventy-five plasma is unbound and and refractory hypocalcemia.6”#{176} for maintaining magnesium percent of magnesium freely filtered at the level intracranial effectively excluded. following hemodialysis level further in our 1)atients pattern as clear, played As with and clinical course but suggests that a significant the first patient, was present susceptible role iii the underlying and may have to the effects of our knowledge only two previously reported describe symptomatic hypermagiiesemia as a result of treatment with OAC and magnesium-containing cathartics.9,16 Both of those cases occurred in patients The in of without renal disease and resulted in either respiratory failure or prolongation of ventilatory support. In one case, diminished bowel function due to tricyclic overdose may have contributed to magnesium toxicity. 16 CHEST Downloaded From: http://publications.chestnet.org/ on 09/09/2014 elevated were absorpproblem. signifiand sinus in partic- To profound hypomotility, and toxicity dysfunction patient more cases include sounds magnesium course. The may bowel of serum hypermagnesia hypermagnesemia. be rate been was the dominant cause for hypotension. it is difficult to determine to what extent hypermagnesemia contributed to the refractory hypotension ohserved in this case. However, with serum magnesiuni levels greater than 10 mg/dl, it is reasonable to assume dis- can disease role ofmagnesiuin The hemodynamic second case is not an iatrogenic hypotension,7’8 weakness and infarction, hypovolemia, of hypotensiori normalization supports order resulting from the use of magnesium-containing medications in the setting of renal impairment.6 effects renal glomerular filtration the magnesium had to absent myocardial pressure and The resolution patient’s aureus. is frequently preexisting effective zero after and hypotension with associated derenal perfusion and oliguria had ensued. patients developed diminished bowel activity judged that necrosis. DISCUSSION Hypermagnesemia or ‘#{176} ‘ sepsis were rod. the acute was cultures hemodialysis 48 occur excretory hypermagof normal absence of stools) shortly into their courses. While likely multifactoral in etiology, hypermagnesemia was probably a contributing factor. Further, the absence of and of 900 with by hypermagnesemia was and cardiac Hg, a Gram-negative contribution status patient toxicity. aspiration, aureus possible mg/dl, revealed the There gluconate. renal ular of a serum resistance and antibiotics. calcium for Staphylococcus Although persisted, renal function.9 cases we described, the and symptomatic in the setting normal creatiniiie large serum had 10 mm infusions 6 g/day), the Moreover, serum and 1.5 vascular when clear- ofa serum measurement during may near-normal In the (as occurs nil/ruin. overcome nesemia creased Both setting mg/dl); had of may (about creatiniiie iii (in the magnesium intake) falls below 30 the levels and, of parathyroid mEq/L; count creatinine, mg/dl; creatinine, a systemic taken IV 3.3 to decreases even reabvaries Serum inagnesiu in levels in a physiologic range, l)ut to excrete a magnesium load hypermagnesemia loads is then of Inagilesium in serum magnesium with the effects capacity administered of which catharsis may have led to further magnesium tion from the gut, thereby compounding the In case 1 it appears that hypermagneseinia cantly contributed to refractory hypotension bradycardia. Other causes for hypotension, infil- ventilated. 10.3 pressure re- bilateral patient catheter and ensued a WBC 5.3 the the to the 44 mg/dl; to serum artery Hypotension treated transferred potassium, before later administration BUN, increasing was a systolic mechanically phosphate, and levarterenol). positive serum (later week hours values: shift; A by a single developed and On patient with was following left serum the followed fluid subsequently (measurement 5) Lung and was absent, but likely approached nausea. tachyarrhythmias the artery of 3.5 (desscm to Pulmonary pulmonary output patient was intubated One level 24 mg/dl. a mean and mWdl; and A a day. and g). Several The mg/dl; twice tachycardic responded a marked mg/dl; 7.6 (17.5 and Hg. included magnesium, calcium, tube film, with orally noted She x-ray Maintenance anorexia Supraventricular data 7,200/cu p.g/ml citrate cardioversion. pneumotho- to a ward. was mm failure. by right dependence. 30 g via an enteral initially infusion. quiring of44 respiratory ventilator mg developed unresponsive of 65 ICU and 300 patient activated acute moved TheoDur, the given Medical with pulmonary disease Unit at Wilford Hall complicated failure, included hospital 1987 ensued heart she medications chronic obstructive Intensive Care majority excretn)n proportionally magnesium 2 rax, falls dietary clearance with deficits. the fractional changes extent, hormone and are normally maintained the ability ofthe kidneys ance, hemodynamic months glomerulus, sorbed. The greatly with to a minimal I 95 I 1 I JANUARY, 1989 57 There is little ing the OAC.’7” ticularly ingestions, practice. ages evidence the literature iii demonstratof par- in the setting of sustained-release tablet and it will likely continue to be a common While firm guidelines delineating the dos- of these cathartics amount of magnesium in case 1 exceeded limit. magnesium developed ‘ have not been established, citrate received by the the generally The second magnesium of 17.5 dosage recommended patient, after which intoxication g of magnesium recommendations. citrate, the patient In a study of normal charcoal, sulfate sorbitol was or magnesium transit time Goldberg combination OAC alone and a single is within in Studies on to be effective balance We are and marked We nesemia in this setting may occur of regularity, but may go unrecognized with to the serum toxicity of the ingested magnesium levels are Review regarding of the clinical and the use of cathartic with OAC leads sorbitol should us to conclude, be considered choice in the treatment including those caused not recom- degree of the associated many attributed drug or toxin because routinely obtained. as have others,’24 that the cathartic agent of of drug toxicities compounds. If 58 Downloaded From: http://publications.chestnet.org/ on 09/09/2014 Cooper of theophylline Crit Jf KR. Care J Treatment Chest Med 1984; J Pediatr clearance Med 1982; 94:314-16 drugs with activated 307:676-78 Cliii WE. 87:325-29 of theophylline 1979; of pharinacokinetics \Vacker of theophylline 1985; M. Inhibition charcoal. intoxications. JR Swartz of oral Pharmacokinet Excess R, Arky ofrefractory Bourgeois activated 1982; magnesium. BA. char- 7:465-89 Pharmacol Extreme Ann hypotension. FJ, Thaigarajah hypotetision 1986; 9 Fassler CA, Rev hyperinagnesensia Med Intern tioii. as 1975; 83:657- 11 Med 1985; FR Magnesium 1981. BS, Coburn RE, jW J Med Cohen in renal I 15 Pollack WJ, and deficiency Spray JJ. Marini hypoventila- and the CC, excess. Annu mimic/antagonist Rossmeisl Intern C, and HH. Stone Med Oh T. EC. 1964; Hart J Br Med 1984; Hyperinag- 61:73-87 C, hypophosphatemia Aspiration of 310:1253-54 Ann Bhagat sulfate. 1986; DB, Magnesium, MD, Hyperinagnesemia 14 Harsch Obstet 145:1604-96 1984; failure. Garcia-Webb magnesium J 32:245-59 N Engl Randall C. Profound Am of hypotension Singer Levine Med Badesch a cause Intern nesernia 13 as RK, calcium. 12 RM, toxicity Med DiFazio therapy. 154:919-20 Arch Rude GM, Harbert magnesium Rodriguez Magnesium 10 S. complicating Gynecol Thompson after W ingestion of 288(6149):759 ofactivated charcoal [Letter]. J N Engl 314:318 MM, of activated Dunbar BS, Holbrook charcoal and gastric PR, Fields contents. Al. Ann Aspiration Emerg Med 1981; 10:528-29 J, 16 Jones Heiselman magnesium Med 17 D, 1986; 18 Effects of tract Toxicol Clin Van Graaff de Eddy overdose A. Cathartic-induced management. Ann Emerg 15:1214-18 JJ. Stewart J, Dougherty during toxicity gastrointestinal Leickly F, enteral drug emetic and Toxicol 1983; WB, and the H. of agents toxic on the J ingestion. 20:199-253 Thompson Dayton cathartic treatment WL, J absorption. Sunshine and Adsorbent Pharmacol 1, Fretthold cathartic Exp D, of inhibition Ther 1982; 221:656- 63 19 experimental literature agents in conjunction of a variety by theophylline to 58 8 hypermag- some because nonspecific nature of symptoms and signs with elevated magnesium levels. Furthermore, of the clinical findings may be incorrectly due 29:273-300 Rev The that occur Treatment charcoal. PJ. Clinical in acute a cause of suspension were toxicity resulting CK. L, Weinberger N Engi 7 Mordes two when FL, Gastrointestinal 6 Mordes hypernatremia. suspect not charcoal. activated by activated C. 1978; ofonly’ oral C, Hendeles coal the thais sus- Mahutte activated Clauser 5 Neuvonen CI oral with charcoal. mean JM, CN, absorption to of the san#{236}e charcoal dosage (1 gfkg) mixed in 4.3 ml! kg body weight of35 percent sorbitol.2 We described two cases in which the treatment of theophylline intoxication with OAC and magnesiumcontaining cathartics resulted in or contributed to hypotension. does also are 14 3 Sintek mended dosage in adults is 1 g/kg ofactivated charcoal in 4.3 mI/kg body weight of 70 percent sorbitol every four hours. The recommendation in children consists refractory catharsis Berman toxicity Furthermore, a prerequisite.2 should agents toxicity function. with 2 Sessler adults show activated charcoal-sorbitol and safe, although appropriate attention is still in the REFERENCES RJ, 12:113’ activated aware use magnesium-containing but bowel 1 rrue magnesium fullowing administration in pediatric patients of charcoal-sorbitol treatment of drug for dehydration to fluid receiving to either in reducing their Magnesium when administered dose the charcoal 2 efkcts occurred doses severe volunteers superior citrate theophylline. administered toxicity. 4 Levy inducing reports of’ adverse sorbitol.2’ 2.5 Both excessive activated employed, 30-g however, and colleagues demonstrated that ofsorbitol and OAC is more effective in enhanciiig elimination of ingested tamed-release magnesium be anticipated toxicity It can be mixed with a more palatable slurry ingestion. are hemodynainically unstable, intoxicated patient should be judicious, with close monitoring of serum magnesium levels and observation for clinical evidence of decreased A therapeutic alternative to magnesium-containing cathartics is the use of soi’bitol, a poorly absorbed sugar which acts as an effective osmotic agent following produce cathartics magnesium efficacy of adding a cathartic to a regimen Nonetheless, their use appears logical, Flomenbauin N, toxicologic Schwartz CR, ed. 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Toxicity 1987; of sorbitol-charcoal suspension. [Letter]. J 111:307-08 Plan to Attend 55th Annual Scientific AssemblyXVI World Congress on Diseases of the Chest Boston . October 30-November 2, 1989 CHEST Downloaded From: http://publications.chestnet.org/ on 09/09/2014 I 95 I 1 I JANUARY, 1989 59
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