Treatment of Ventricular Fibrillation Due to Ammonium Bifluoride Poisoning with Hemodialysis Andrew N
Treatment of Ventricular Fibrillation DueAndrew N. Farkas, to MD, Ammoniuma Michael S. Wolf, MD,b Elizabeth Landzberg, Bifluoride MD,c Michael J. Lynch, MD, a Kendra S. Woods, MDb
Poisoning With Hemodialysisabstract Ammonium bifluoride is an inorganic, fluoride-containing compound found in glass and metal etching products, as well as wheel cleaners. Fluoride toxicity is a common cause of preventable poisoning and has been reported to cause life-threatening ventricular dysrhythmias. Here, we report a case of recurrent ventricular fibrillation secondary to ingestion of ammonium Divisions of aMedical Toxicology and bPediatric Critical bifluoride. The patient presented with vomiting and coma. She was Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and cDepartment of Pediatrics, intubated for altered mental status and respiratory failure and subsequently Children’s Hospital of Pittsburgh of University of Pittsburgh had 5 episodes of ventricular fibrillation, each resolving with a single Medical Center, Pittsburgh, Pennsylvania defibrillation. She developed metabolic acidosis and hypocalcemia, which ’ Dr Farkas drafted the initial manuscript; were treated with sodium bicarbonate and calcium gluconate, respectively. Dr Landzberg prepared the figure; all authors During transfer to a tertiary care children s hospital, ventricular fibrillation reviewed and revised the original manuscript and participated equally in conceptualizing and recurred despite electrolyte correction. Hemodialysis (HD) was initiated organizing this case report and the final review emergently. No further dysrhythmia occurred after initiation of HD. The and revision of the manuscript; and all authors result of a basic urine drug screen was negative, and a comprehensive approved the final manuscript as submitted and agree to be accountable for all aspects of the work. drug screen (gas chromatography and mass spectroscopy) revealed only a DOI: https://doi.org/10.1542/peds.2018-0136 nonsignificant peak for diphenhydramine. Subsequent laboratory evaluation revealed an elevated serum fluoride level. Diagnostic laryngoscopy Accepted for publication May 29, 2018 and upper endoscopy did not reveal evidence of caustic injury. She was Address correspondence to Michael S. Wolf, MD, Division of Pediatric Critical Care Medicine, successfully extubated on hospital day 2 and discharged from the hospital Children’s Hospital of Pittsburgh of University of on day 4 with no neurologic sequelae. With this example, we demonstrate a Pittsburgh Medical Center, 4401 Penn Ave, Faculty potential therapeutic approach to this potentially lethal poisoning. Fluoride Pavilion, Suite 2000, Pittsburgh, PA 15224. E-mail: [email protected] toxicity is typically treated with calcium. However, dysrhythmia may result from calcium-independent direct myocardial toxicity. The kinetics of PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). fluoride are amenable to HD, and renal clearance is slow. The potential use Copyright © 2018 by the American Academy of of HD in cases of fluoride poisoning refractory to other therapies warrants Pediatrics further study. FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
Ammonium bifluoride is an inorganic of dysrhythmia is thought to be FUNDING: Dr. Wolf was supported by National 3 Institutes of Health grant T32 HD040686; however, no compound found in glass and metal secondary to hypocalcemia via funding was obtained for this case report. etching products, as well as wheel fluorapatite formation and/or binding 1 POTENTIAL CONFLICT OF INTEREST: The authors cleaners. Fluoride poisoning is of calcium leading to precipitation of 4 have indicated they have no potential conflicts of a common2 cause of preventable insoluble calcium fluoride into tissues. interest to disclose. poisoning. There are scant reports However, a direct cardiotoxic effect of ingestions of ammonium bifluoride of fluoride has also5,6 been implicated To cite: Farkas AN, Wolf MS, Landzberg E, et al. (or other common sources of in animal studies. We report a Treatment of Ventricular Fibrillation Due to Ammo fluoride such as hydrofluoric acid) rare case of ingestion of a product nium Bifluoride Poisoning With Hemodialysis. Pedi causing ventricular dysrhythmias containing ammonium bifluoride, atrics. 2018;142(3):e20180136 likely because of the rare incidence successfully treated with elimination of such ingestions. The mechanism via hemodialysis (HD) after recurrent Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 142, number 3, September 2018:e20180136 CASE REPORT
co o ventricular fibrillation occurred bicarbonate (25 mEq), and started 7.59, P 2 of 29 mmHg, P 2 of ∼ despite correction of hypocalcemia. on a bicarbonate infusion. Then, 236 mmHg, and a bicarbonate CASE REPORT 90 minutes after arrival, she had a level of 28 mmol/L. The patient brief ventricular fibrillation cardiac was also noted to have marked arrest, which was successfully hypophosphatemia (0.9 mg/dL) treated with a 50-J defibrillation. requiring aggressive repletion. A 21-kg 4-year-old girl with no Thereafter, a second bolus of 1.6 g A fluoride level obtained 90 minutes pertinent past medical history calcium gluconate was given; 110 into HD was 0.37 mg/L (reference presented to an emergency minutes after arrival, there were 2 range <0.2 mg/L). The result of department with vomiting and coma “ ” additional episodes of ventricular a basic urine drug screening was shortly after ingestion of reportedly ’ fibrillation treated with 50- and negative, and a comprehensive urine just a sip of a chemical being stored “ ’ 85-J defibrillation, respectively. drug screen (gas chromatography/ in her family s garage. This chemical ’ A continuous infusion of calcium mass spectroscopy) revealed was later identified as Meguiar s ” gluconate at 400 mg per hour was only a nonsignificant peak of Professional s Choice Detailer, ∼ then started, and she was treated diphenhydramine. Electrocardiogram Wheel Brightener, with the safety with a total of 4 g of magnesium that was obtained 6 hours after data sheet indicating the presence – sulfate. A repeated ionized calcium initial presentation revealed sinus of 5% to 10% ammonium bifluoride – level was 1.33 mmol/L. tachycardia at a rate of 123, QRS as well as water (70% 90%), – duration of 82 ms, and QT and sodium xylene sulfonate (1% 5%), The patient was then transported QTc intervals of 304 and 435, ethoxylated alcohols (0.5% 1.5%), via air ambulance with a pediatric respectively, without ST segment and ammonium fluoride (<0.5%). On ’ ° critical care transport team to a or T wave abnormalities; ionized arrival, the patient had vital signs of tertiary children s hospital and calcium was 1.39 mmol/L at temperature (35.9 C), blood pressure required 2 additional defibrillations that time. (75 over 39 mmHg), pulse (87 for ventricular fibrillation en route beats per minute), respiratory rate There were no further episodes despite the ongoing infusion of (6 breaths per minute), and pulse of dysrhythmia after initiation calcium gluconate (although no oximetry (98% on a nonrebreather of HD, and the patient remained additional bolus dosing was given). face mask). The physical examination hemodynamically stable (Fig 1). Immediately on arrival to our PICU, was notable for obtundation, the The patient underwent diagnostic a point-of-care ionized calcium was presence of vomitus, and recent fecal ’ laryngoscopy and upper endoscopy found to be 1.23 mmol/L. Five hours incontinence. The patient was given revealing no evidence of caustic after the patient s initial emergency intravenous normal saline boluses injury. She was successfully department arrival, the patient was for hypotension, with the lowest extubated on hospital day 2 and placed on HD; hemodynamics were measured pressure being 45 over discharged from the hospital on day 4 deemed sufficient for intermittent 31 mmHg. She was intubated for with no neurologic sequelae. HD (heart rate was 130 beats per respiratory depression and airway minute, and blood pressure was 95 DISCUSSION protection. Blood work obtained over 33 mmHg). The treatment was shortly after arrival revealed an provided with a Fresenius Optiplex arterial blood gas with a pH of co o 16NR dialyzer via a 9 French, 12-cm Ammonium bifluoride ingestions 7.156, P 2 of 44.3 mmHg, P 2 of catheter placed in the left femoral have been previously reported 115.7 mmHg, and bicarbonate level vein. The treatment was performed to cause central nervous system of 15.7 mmol/L. This metabolic with blood flow at 200 to 250 mL per depression, hypocalcemia, and acidosis occurred despite a normal 1 minute, dialysate flow at 800 mL per ventricular dysrhythmia. Although lactate (1.1 mmol/L). A point-of-care minute, and no ultrafiltration for 4 there were other ingredients present ionized calcium was 0.88 mmol/L. hours with dialysate concentrations within the wheel cleaner ingested in Serum chemistries were notable for of sodium 139 mmol/L, potassium this case, they were minimally toxic a potassium level of 3.4 mmol/L, ’ 4 mmol/L, bicarbonate 35 mmol/L, and unlikely to have contributed magnesium level of 2.2 mg/dL, – and calcium 3.5 mmol/L. Additional to the patient s presentation. This calcium level of 6.0 mmol/L (range: μ testing obtained on arrival included case of ammonium bifluoride 8.8 10.8), and bicarbonate level of – an ammonia level of 35 mol/L, poisoning is unique in that it reveals 18 mmol/L with an anion gap of lactate level of 4.2 mmol/L, at least 2 episodes of ventricular 16 mEq/L (range: 5 25). potassium level of 3.0 mmol/L, and a fibrillation that occurred despite The patient was given 1.6 g of negative toxic alcohol panel. A repeat normal serum values of ionized calcium gluconate, a bolus of sodium serum blood gas revealed a pH of calcium and magnesium (with Downloaded from www.aappublications.org/news by guest on September 26, 2021 2 FARKAS et al In this case, the 2 additional cardiac ’ arrest events after calcium repletion were likely due to fluoride s direct cardiotoxic effects. A canine model of fluoride toxicity has revealed
ventricular fibrillation6 despite normal calcium levels, and repletion of calcium and magnesium did not
prevent dysrhythmia and death from4 fluoride poisoning in a porcine model. The etiology of these dysrhythmias is thought to be related to intracellular hypocalcemia and direct inhibition
of the calcium-dependent6 potassium channel by fluoride.
Given the concern that our patient was experiencing potentially fatal dysrhythmias because of the direct effect of a xenobiotic rather than via electrolyte disturbance, HD was initiated to enhance elimination of the suspected offending agent. The efficacy of HD in this scenario is FIGURE 1 supported by the fact that no further Graph of serum ionized calcium level over time. Diamonds are used to indicate measured ionized ventricular dysrhythmia occurred calcium levels. “X” is used to indicate an episode of ventricular fibrillation. Triangles are used to after HD was initiated, although indicate calcium gluconate boluses. Horizontal bars are used to represent HD course and calcium the causality of this association gluconate infusion duration. is uncertain and is potentially attributable to the natural course of the illness. Nonetheless, the kinetic attributes of fluoride are favorable serum ionized calcium found to be hypophosphatemia via fluorapatite for extracorporeal removal via HD, 4 – above 1.2 mmol/L before and after formation. Alkalinization via with a low volume of distribution
2 cardiac arrests). In our patient, bicarbonate infusion can also cause (0.5 0.710 L/kg), lack of protein mild hypokalemia was present, hypophosphatemia9 as shown in a binding,11 and small molecular but the degree of hypokalemia is canine model and therefore could weight (19 g/mol). Because renal unlikely to have independently have been contributing because clearance of fluoride is only 50%11 in produced ventricular fibrillation. bicarbonate was given in this case; the 24 hours after ingestion, it is Hypophosphatemia was also however, it was probably not the plausible that even in the presence present, and authors of a small sole cause given the severity of the of normal renal function, high-flow study have shown an association abnormality that was observed. HD would significantly improve with dysrhythmia7 in adult septic Metabolic acidosis was identified clearance. Previously, the same patients. Hypophosphatemia may after initial laboratory studies approach has been used in cases of have contributed to the tendency despite a normal lactic acid level poisoning by 2 different fluoride- for dysrhythmia in this case but and before cardiac arrest indicating containing12,13 products, hydrofluoric14 was unlikely the sole cause of that acidosis was not a result of acid and sodium fluoride, which the dysrhythmias observed. The tissue hypoperfusion. Given that were successfully treated with HD. causality of the hypophosphatemia ammonium bifluoride is an acid Conversely, in a case of fluoride is unclear. Sodium fluoride infusions with a pH of 2, alternative etiologies poisoning from sodium silicofluoride, have been shown to increase, rather include the direct absorption of peritoneal dialysis was ineffective15 in than decrease serum phosphate8 acid with resulting circulating enhancing elimination of fluoride. levels in 1 animal model ; however, unmeasured acid and the release There is scant evidence regarding authors of an in vivo study implicated of free hydrogen ions through4 the ammonium bifluoride toxicity, that hydrofluoric acid induced formation of fluorapatite. and management with HD has not Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 142, number 3, September 2018 3 REFERENCES calcium, inorganic phosphate, and ionic fluoride. Calcif Tissue Int. 1. Maddry JK, Kester A, Heard K. previously been reported. Because 1987;41(2):105 111 Prolonged hypocalcemia refractory – HD offers higher clearance rates to calcium gluconate after 9. Fulop M, Brazeau P. The phosphaturic than continuous renal replacement ammonium bifluoride ingestion in a effect of sodium bicarbonate and therapy, it would also be expected pediatric patient. Am J Emerg Med. acetazolamide in dogs. J Clin Invest. to offer superior efficacy when rapid16 2017;35(2):378.e1–378.e2 1968;47(5):983–991 removal of a xenobiotic is desired. 2. Srisuma S, Cao D, Kleinschmidt 10. Ekstrand J, Ericsson Y, Rosell S. However, in cases of poisoning K, Heffner AC, Lavonas EJ. Missed Absence of protein-bound fluoride with persistent hemodynamic opportunities?: an evaluation of from human and blood plasma. Arch instability, extracorporeal potentially preventable poisoning Oral Biol. 1977;22(4):229–232 membrane oxygenation combined deaths. Clin Toxicol (Phila). 11. Martínez MA, Ballesteros S, Piga FJ, with continuous renal replacement17 2016;54(5):441–446 Sánchez de la Torre C, Cubero CA. therapy can be considered. The 3. Klasaer AE, Scalzo AJ, Blume C, The tissue distribution of fluoride in lack of a postdialysis fluoride level is Johnson P, Thompson MW. Marked a fatal case of self-poisoning. J Anal a limitation of this report; however, hypocalcemia and ventricular Toxicol. 2007;31(8):526–533 there is historical and theoretical fibrillation in two pediatric patients 12. Björnhagen V, Höjer J, Karlson- basis for the efficacy13 of fluoride exposed to a fluoride-containing Stiber C, Seldén AI, Sundbom M. wheel cleaner. Ann Emerg Med. CONCLUSIONSremoval via HD. Hydrofluoric acid-induced burns 1996;28(6):713–718 and life-threatening systemic 4. Coffey JA, Brewer KL, Carroll R, poisoning–favorable outcome after Bradfield J, Meggs WJ. Limited hemodialysis. J Toxicol Clin Toxicol. We describe a rare case of central efficacy of calcium and magnesium 2003;41(6):855–860 nervous system depression, in a porcine model of hydrofluoric 13. Antar -Shultz M, Rifkin SI, McFarren C. metabolic acidosis, and recurrent acid ingestion. J Med Toxicol. Use of hemodialysis after ingestion ventricular fibrillation arrest 2007;3(2):45–51 of a mixture of acids containing secondary to ingestion of ammonium 5. Strubelt O, Iven H, Younes M. The hydrofluoric acid. Int J Clin Pharmacol bifluoride confirmed by serum pathophysiological profile of the Ther. 2011;49(11):695–699 fluoride testing. Notably, there was acute cardiovascular toxicity 14. Berman L, Taves D, Mitra S, Newmark no hyperammonemia or caustic of sodium fluoride. Toxicology. K. Inorganic fluoride poisoning: injury observed. With this patient, 1982;24(3–4):313–323 treatment by hemodialysis. N Engl J correction of hypocalcemia did not 6. Cummings CC, McIvor ME. Fluoride- Med. 1973;289(17):922 prevent dysrhythmia, but no further induced hyperkalemia: the role of 15. Yolken R, Konecny P, McCarthy P. episodes of dysrhythmia occurred Ca2+-dependent K+ channels. Am J Acute fluoride poisoning. Pediatrics. after initiation of HD. Accordingly, Emerg Med. 1988;6(1):1–3 1976;58(1):90–93 HD should be considered in cases of 7. Schwar tz A, Brotfain E, Koyfman 16. Basu RK, Wheeler DS, Goldstein S, ammonium bifluoride poisoning if L, et al. Association between Doughty L. Acute renal replacement toxicity persists despite correction hypophosphatemia and cardiac therapy in pediatrics. Int J Nephrol. of hypocalcemia. Additionally, arrhythmias in the early stage of 2011;2011:785392 serum phosphate levels should be sepsis: could phosphorus replacement 17. Pu Q, Qian J, Tao W, Yang A, Wu J, closely monitored and corrected in treatment reduce the incidence of Wang Y. Extracorporeal membrane fluoride poisoning given the potential arrhythmias? Electrolyte Blood Press. oxygenation combined with continuous for arrhythmogenic effects from 2014;12(1):19–25 renal replacement therapy in hypophosphatemia. 8. Monsour PA, Smid JR, Kruger BJ. cutaneous burn and inhalation injury ABBREVIATION The effect of intravenous sodium caused by hydrofluoric acid and fluoride and synthetic salmon nitric acid. Medicine (Baltimore). calcitonin on plasma total 2017;96(48):e8972 HD: hemodialysis
Downloaded from www.aappublications.org/news by guest on September 26, 2021 4 FARKAS et al Treatment of Ventricular Fibrillation Due to Ammonium Bifluoride Poisoning With Hemodialysis Andrew N. Farkas, Michael S. Wolf, Elizabeth Landzberg, Michael J. Lynch and Kendra S. Woods Pediatrics 2018;142; DOI: 10.1542/peds.2018-0136 originally published online August 15, 2018;
Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/142/3/e20180136 References This article cites 17 articles, 1 of which you can access for free at: http://pediatrics.aappublications.org/content/142/3/e20180136#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Critical Care http://www.aappublications.org/cgi/collection/critical_care_sub Pharmacology http://www.aappublications.org/cgi/collection/pharmacology_sub Toxicology http://www.aappublications.org/cgi/collection/toxicology_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml
Downloaded from www.aappublications.org/news by guest on September 26, 2021 Treatment of Ventricular Fibrillation Due to Ammonium Bifluoride Poisoning With Hemodialysis Andrew N. Farkas, Michael S. Wolf, Elizabeth Landzberg, Michael J. Lynch and Kendra S. Woods Pediatrics 2018;142; DOI: 10.1542/peds.2018-0136 originally published online August 15, 2018;
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/142/3/e20180136
Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2018 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.
Downloaded from www.aappublications.org/news by guest on September 26, 2021