This article was downloaded by: [Wallace, Erik A.] On: 13 April 2009 Access details: Access Details: [subscription number 909751137] Publisher Informa Healthcare Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK Clinical Toxicology Publication details, including instructions for authors and subscription information: http://www.informaworld.com/smpp/title~content=t713597279 Methanol toxicity secondary to inhalant abuse in adult men Erik A. Wallace a; Adam S. Green b Department of Internal Medicine, University of Oklahoma College of Medicine, Tulsa, OK, USA b Department of Radiology, Worcester Medical Center, St. Vincent Hospital, Worcester, MA, USA a First Published:March2009 To cite this Article Wallace, Erik A. and Green, Adam S.(2009)'Methanol toxicity secondary to inhalant abuse in adult men',Clinical Toxicology,47:3,239 — 242 To link to this Article: DOI: 10.1080/15563650802498781 URL: http://dx.doi.org/10.1080/15563650802498781 PLEASE SCROLL DOWN FOR ARTICLE Full terms and conditions of use: http://www.informaworld.com/terms-and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, re-distribution, re-selling, loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Clinical Toxicology (2009) 47, 239–242 Copyright © Informa UK, Ltd. ISSN: 1556-3650 print / 1556-9519 online DOI: 10.1080/15563650802498781 Methanol toxicity secondary to inhalant abuse in adult men LCLT ERIK A. WALLACE1 and ADAM S. GREEN2 Methanol toxicity secondary to inhalant abuse 1 Downloaded By: [Wallace, Erik A.] At: 15:00 13 April 2009 2 Department of Internal Medicine, University of Oklahoma College of Medicine, Tulsa, OK, USA Department of Radiology, Worcester Medical Center, St. Vincent Hospital, Worcester, MA, USA Background. The purpose of this report is to evaluate the presentation, treatment, and outcomes of adults with methanol toxicity from inhalation of carburetor cleaning fluid fumes. Methods. Retrospective chart review of adults with positive serum volatile screen for methanol and history of carburetor cleaning fluid fume inhalation. Results. Sixteen patients were admitted 68 times. Eleven Native American patients accounted for 90% of admissions. Sixty-five cases presented with nausea/vomiting; 27 with intoxication or altered mental status; 21 with specific visual complaints. About 93% had a pH <7.35, 96% had serum bicarbonate <20 mEq/L, 81% had osmolal gap ≥10 mOsm/L, and 69% had anion gap >16. Ten had an initial serum methanol level <20 mg/dL, 29 cases 20–49 mg/dL, 19 cases ≥50 mg/dL. Six patients had a measurable serum ethanol level. Of the 29 patients with a methanol level of 20–49 mg/dL, 20 received intravenous antidote (ethanol or fomepizole); three received an antidote and hemodialysis. All who presented with a serum methanol level ≥50 mg/dL received intravenous ethanol or fomepizole. All visual symptoms resolved before discharge and all patients survived without sequelae. Discussion. This is the largest reported number of cases of methanol toxicity from the inhalation of carburetor cleaning fluid fumes and demonstrates a problem with recurrent abuse among some older Native American men. Conclusion. Intentional inhalation of methanol fumes may produce toxicity. Clinicians need to question patients, especially older Native American men, regarding the possible inhalation of carburetor cleaning fluid fumes in those who present with an unexplained metabolic anion gap acidosis. Keywords Methanol toxicity; Carburetor; Inhalant abuse; Native American Introduction Methods Inhalant abuse continues to be a problem in the United States. More than one million people abuse inhalants each year, the majority of whom are Caucasian and Hispanic adolescents.1–4 However, inhalant abuse among adults is uncommon.1 More than 1,000 products, some of which contain methanol, are available for abuse as inhalants and can produce varying degrees of toxicity, although methanol toxicity is uncommon.5 Treatment guidelines that include the use of intravenous ethanol, fomepizole, and hemodialysis are based primarily on the patient’s serum methanol level on presentation.6,7 However, outcomes associated with inhalational methanol toxicity have not been studied since the vast majority of methanol cases are a result of ingestion. In this report, we describe the presentation, treatment, and outcomes of adults who presented to a community hospital with methanol toxicity from the inhalation of carburetor cleaning fluid fumes. The medical records of adults (age ≥18 years old) who were admitted to St. John Medical Center in Tulsa, Oklahoma from January 1, 2000 through December 31, 2006, with a positive serum volatile screen for methanol were reviewed. The inclusion and exclusion criteria are shown in Fig. 1. Variables identified and analyzed were age, sex, race, number of admissions per patient, location of admission, treatment received, clinical outcome, and the admission arterial pH, serum bicarbonate (mEq/L), anion gap, serum osmolality (mOsm/L), serum methanol (mg/dL), and serum ethanol (mg/dL). Serum osmolal gap was reported as calculated serum osmolality (mOsm/L) minus measured serum osmolality (mOsm/L) where calculated serum osmolality = (2 × (Na + K)) + (BUN/2.8) + (glucose/18). Statistical analyses were carried out using StatsDirect statistical software (http://www.statsdirect.com) (StatsDirect Ltd, England) in 2008. Values are reported as percentage or mean (SD), with p < 0.05 considered statistically significant. The institutional review boards of The University of Oklahoma and St. John Medical Center approved this study. Received 26 June 2008; accepted 23 September 2008. Address correspondence to Erik A. Wallace, Department of Internal Medicine, University of Oklahoma College of Medicine, 4502 E. 41st Street, Tulsa, OK 74135, USA. E-mail: erik-wallace@ouhsc.edu Results Sixty-nine patients were identified (Fig. 1). One patient who had a positive serum volatile screen for methanol was Clinical Toxicology vol. 47 no. 3 2009 240 E.A. Wallace and A.S. Green Patients identified with positive serum volatile screen for methanol (n = 69) Patients admitted with diagnosis of inhalant abuse or methanol toxicity (n = 69) Patients who inhaled products that did not contain methanol by history (n = 1) Patients who inhaled carburetor cleaning products containing methanol by history (n = 68) Downloaded By: [Wallace, Erik A.] At: 15:00 13 April 2009 No serum methanol level measured on admission (n = 10) Patients with measured serum methanol level on admission (n = 58) Serum methanol <20 mg/dL (n = 10) Treatment with antidote (n = 20) Serum methanol ≥50 mg/dL (n = 19) Serum methanol ≥20 and <50 mg/dL (n = 29) Treatment with antidote and hemodialysis (n = 3) Treatment without antidote or hemodialysis (n = 6) Treatment with antidote and hemodialysis (n = 12) Treatment with antidote and no hemodialysis (n = 7) Antidote = intravenous ethanol or fomepizole Fig. 1. Study flow diagram and treatment record. excluded because the inhalant used by this patient did not contain methanol by history and the serum methanol concentration was negative. Ten patients were included who did not have a serum methanol concentration measured on admission. The inhalation of carburetor cleaning fluid containing methanol was confirmed by history in the 68 admissions. Sixteen patients were admitted 68 times for methanol toxicity from the inhalation of carburetor cleaning fluid containing methanol (Table 1). All 16 patients were men, and 11 patients (69%) were Native Americans. The mean age at first admission during this time period was 38 years (SD 9, range 22–49). The mean number of admissions per patient was four (SD 3, range 1–12). Native American patients accounted for more admissions per patient compared with non-Native American patients (chi-square, p < 0.0001). In 21 of the 68 cases, patients reported specific visual complaints; in 20 of the 68 cases, patients specifically denied any visual complaints; and in the remaining 27 of 68 cases, patients were “intoxicated” or a review of systems was “unobtainable” because of their altered mental status. Although none of the patients received a formal ophthalmology exam, all visual symptoms resolved before discharge regardless of the severity of methanol toxicity or treatment received. Sixty-five cases presented with nausea and vomiting. Only 3 of the 68 cases denied nausea and vomiting on presentation. The laboratory values obtained on admission are shown in Table 2. Most patients presented with pH <7.35 (92%), serum bicarbonate <20 mEq/L (96%), osmolal gap ≥10 mOsm/L (81%), and anion gap >16 (69%). Measured serum methanol levels were obtained in only 58 of the 68 admissions (85%). Of these 58 admissions, 10 cases (17%) had an initial serum methanol level <20 mg/dL, 29 cases (50%) between 20 and 49 mg/dL, and 19 cases (33%) had an initial serum methanol level ≥50 mg/dL. Only six patients (9%) presented with a measurable serum ethanol level. Serum formic acid levels were not measured. Clinical Toxicology vol. 47 no. 3 2009 Methanol toxicity secondary to inhalant abuse 241 Table 1. Patient demographics Number of patients 16 Gender Age at first admission, years (mean (SD)) Race Men Native American Caucasian Hispanic Unknown Number of admissions Native American Non-Native American Number of admissions per patient (mean (SD)) Native American Non-Native American 16 (100%) 38 (9), range 22–49 11 (69%) 3 (19%) 1 (6%) 1 (6%) 68 61 (90%)* 7 (10%) 4 (4), range 1–12 6 (4), range 1–12 1 (1), range 1–3 Downloaded By: [Wallace, Erik A.] At: 15:00 13 April 2009 *Chi-square, p < 0.0001. Table 2. Laboratory values on admission HCO−3 (mEq/L) Anion gap Osmolal gap (mOsm/L) Serum methanol (mg/dL) Serum ethanol (mg/dL) All patients (n = 68) Mean (SD) 7.23 (0.11) Range 6.95–7.47 10 (5) 2–25 21 (7) 9–42 25 (17) 0–62 48 (33) 0–164 8 (32) 0–189 Serum methanol <20 mg/dL (n = 10) Mean (SD) 7.32 (0.10) Range 7.18–7.47 13 (5) 9–25 19 (8) 11–36 7 (6) 0–15 9 (5) 0–16 0 0 Serum methanol ³20 and<50 mg/dL (n = 29) Mean (SD) 7.23 (0.09) 10 (5) Range 6.95–7.39 4–21 20 (7) 9–39 19 (10) 19–38 35 (8) 21–49 14 (43) 0–189 Serum methanol ³ 50 mg/dL (n = 19) Mean (SD) 7.20 (0.10) Range 7.02–7.33 24 (7) 15–42 44 (11) 27–62 86 (28) 56–164 5 (20) 0–85 pH 8 (4) 2–15 Forty-six admissions (68%) were to the medical intensive care unit. All patients were treated with intravenous fluids and bicarbonate. Of the 29 patients who presented with a serum methanol level between 20 and 49 mg/dL, 20 patients (69%) were treated with an intravenous antidote (ethanol or fomepizole) and three patients (10%) received an antidote and hemodialysis. Six patients (21%) did not receive treatment with intravenous ethanol, fomepizole, or hemodialysis (Fig. 1). All 19 patients who presented with a serum methanol level ≥50 mg/dL received intravenous ethanol or fomepizole; however, seven patients (37%) did not receive hemodialysis. No patients received folic acid or folinic acid. All patients survived without permanent sequelae. Discussion Although inhalation abuse among adults is uncommon, we identified methanol toxicity from inhalation of carburetor cleaning fluid as a recurrent problem among the Native American adult men studied. Sixty-nine percent of the patients admitted with methanol toxicity from inhaling carburetor cleaning fluid fumes were Native Americans; however, they accounted for 90% of the admissions with an average of six admissions per patient. In addition, the average patient age in this population is higher than previously reported (Table 3) with initial laboratory values on Table 3. Comparison of patient demographics with other case series Study McCormick et al. (8) Frenia and Schauben (9) LoVecchio et al. (10) Bebarta et al. (11) Wallace et al. (12) Patients Cases 1 4 22 7 16 1 7 22 7 68 Men Mean age, years (range) 100% 100% 72.7% 95.7% 100% 17.0 27.6 (26–29) 17.0 (14–41) 29.0 (15–58) 38.4 (22–49) Clinical Toxicology vol. 47 no. 3 2009 Downloaded By: [Wallace, Erik A.] At: 15:00 13 April 2009 242 E.A. Wallace and A.S. Green admission that were similar to previous reports.8–11 Although inhalant use by race is well described in adolescents,2 data on inhalant use by race in adults are not available. In addition, lifetime inhalant abuse among Native American adolescents is unknown as use by race is only provided for white, black, and Hispanic adolescents.2 We believe that the increased age of these patients is significant since it is unlikely that their substance abuse started late in life. Treatment recommendations for methanol toxicity include intravenous sodium bicarbonate and folic or folinic acid. Guidelines indicate that an antidote, preferably fomepizole (rather than ethanol) should be given when the serum methanol concentration is ≥20 mg/dL. Hemodialysis along with an antidote should be initiated when the serum methanol concentration is ≥50 mg/dL.6,7 Previous reports on inhalational methanol toxicity describe outcomes ranging from benign to more serious sequelae including death5,8–11,13 Other authors have suggested that lower levels of serum methanol are achieved through inhalation versus ingestion, thus resulting in lower rates of complications.10,11 However, serum methanol levels ≥50 mg/dL were seen in 19 admissions (28%). No permanent sequelae were observed in these patients despite the fact that seven patients did not receive hemodialysis, which was indicated according to current treatment guidelines.6,7 Because ethanol has a higher affinity for alcohol dehydrogenase than methanol, concurrent abuse of ethanol can delay methanol metabolism into formic acid and subsequent complications of metabolic acidosis. Only 6 out of 68 cases had measurable serum ethanol levels with no difference in outcomes. It is difficult to identify the timeline between the patient’s ingestion/inhalation and their presentation to a health-care facility.14 Although the clinical course between inhalation and ingestion of methanol may differ, current guidelines do not differ between treating these two groups of patients. It is also not known whether pharmacogentics affects morbidity and mortality from methanol toxicity. Limitations Our retrospective chart review has several limitations. Medical records are often incomplete so historical and physical data may have been missing. Data regarding methanol concentration of carburetor cleaning fluids and the quantity of each product inhaled to produce a given methanol level were unavailable. Similarly, the time between inhalation of the carburetor cleaning fluid fumes and admission could not be determined. View publication stats Conclusion Methanol toxicity from inhalation of carburetor cleaning fluid is a recurrent problem among some Native American men. These patients are older than those reported previously, and this represents a patient group in whom the suspicion of methanol ingestion must be entertained when the patient presents with an unexplained metabolic acidosis. Although many clinicians question patients about oral ingestion of methanol, we believe that the suspicion for inhalation of methanol should be high in older Native American men. Future research is needed to determine which factors lead to recurrent inhalant abuse among adults. References 1. Office of Applied Studies, Substance Abuse and Mental Health Services Administration. The national survey on drug use and health report; Patterns and trends in inhalant use by adolescent males and females: 2002–2005; 2007. http://www.oas.samhsa.gov/2k7/inhalants/ inhalants.cfm. Accessed 6 June 2008. 2. Eaton DK, Kann L, Kinchen S, Shanklin S, Ross J, Hawkins J, Harris WA, Lowry R, McManus T, Chyen D, Lim C, Brener ND, Wechsler J. Youth risk behavior Surveillance – United States, 2007. Department of Health and Human Services, Centers for Disease Control and Prevention, 2008. http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5704a1.htm. Accessed 6 June 2008. 3. Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE. Monitoring the future: national results on adolescent drug use. University of Michigan News Service, Ann Arbor, 2008. http://monitoringthefuture.org/ pubs/monographs/overview2007.pdf. Accessed 6 June 2008. 4. The Partnership for Drug Free America. Partnership attitude tracking study: teens 2004. The Partnership for Drug Free America, 2005. http:// www.rwjf.org/files/research/Full%20Report%20PATS%20TEENS% 207th-12th%20grades%202004.pdf. Accessed 6 June 2008. 5. Davis LE, Hudson D, Benson BE, Jones EasomLA, Coleman JK. Methanol poisoning exposures in the United States: 1993–1998. Clin Toxicol 2002; 40:499–505. 6. Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. Clin Toxicol 2002; 40:415–446. 7. Kraut JA, Kurtz I. Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol 2008; 3:208–225. 8. McCormick MJ, Mogabgab E, Adams SL. Methanol poisoning as a result of inhalational solvent abuse. Ann Emerg Med 1990; 19:639–642. 9. Frenia ML, Schauben JL. Methanol inhalation toxicity. Ann Emerg Med 1993; 22:1919–1923. 10. LoVecchio F, Sawyers B, Thole D, Beuler MC, Winchell J, Curry SC. Outcomes following abuse of methanol-containing carburetor cleaners. Hum Exp Toxicol 2004; 23:473–475. 11. Bebarta VS, Heard KH, Dart RC. Inhalational abuse of methanol products: elevated methanol and formate levels without vision loss. Am J Emerg Med 2006; 24:725–728. 12. Wallace EA, Green AS, Methanol toxicity secondary to inhalant abuse in adult men. Clin Toxicol (forthcoming). 13. Liu JJ, Daya MR, Carrasquillo O, Kales SN. Prognostic factors in patients with methanol poisoning. Clin Toxicol 1998; 36:175–181. 14. Kostic MA, Dart RC. Rethinking the toxic methanol level. J Toxicol Clin Toxicol 2003; 41:793–800.