CASE REPORT


https://doi.org/10.5005/jp-journals-11006-0132
Indian Journal of Critical Care Case Report
Volume 3 | Issue 5 | Year 2024

Presentation and Management of Acute Toluene Intoxication: A Case Report


Gursharan Singh1https://orcid.org/0000-0002-2413-4535, Aman Shukla2https://orcid.org/0009-0005-2434-7564, Priyanka H Chhabra3https://orcid.org/0000-0001-9436-6123, Santvana Kohli4https://orcid.org/0000-0003-1410-6933

1–4Department of Anesthesia and Intensive Care, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India

Corresponding Author: Santvana Kohli, Department of Anesthesia and Intensive Care, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India, Phone: +91 7838434398, e-mail: dr.santvana.kohli@gmail.com

Received: 07 July 2024; Accepted: 12 August 2024; Published on: 27 August 2024

ABSTRACT

Aim and background: Commonly found in glues, paints, varnishes and industrial solvents, toluene is a widely abused drug due to its acute neurologic effects including euphoria and subsequent depression. However, its abuse is also associated with dangerous electrolyte and metabolic abnormalities, rhabdomyolysis, acute kidney injury (AKI) and cardiac abnormalities.

Case description: A young lady, chronic inhalational abuser of toluene, presented to our hospital with acute intoxication secondary to ingestion of whitener solution in an unconscious state. She was found to have severe acidemia and hypokalemia, progressing to acute kidney injury (AKI). The patient was admitted in ICU for mechanical ventilation, and correction of electrolyte and metabolic abnormalities. Thereafter, she made a complete recovery and was successfully discharged.

Conclusion: The hallmark of toluene intoxication is a normal anion gap hyperchloremic metabolic acidosis with severe hypokalemia or distal renal tubular acidosis (RTA) type 1. Patients may also develop AKI, rhabdomyolysis and cardiac abnormalities (arrhythmias and ST-T segment changes due to severe hypokalemia), but rarely respiratory depression. Management involves adequate resuscitation, intensive care admission and aggressive correction of acid base and electrolyte abnormalities, as there is no specific antidote.

Clinical significance: Early recognition and management of clinical features and complications like AKI and arrythmias is of utmost importance in patients with toluene intoxication.

Keywords: Acute kidney injury, Case report, Hypokalemia, Poisoning, Renal tubular acidosis, Rhabdomyolysis

How to cite this article: Singh G, Shukla A, Chhabra PH, et al. Presentation and Management of Acute Toluene Intoxication: A Case Report. Indian J Crit Care Case Rep 2024;3(5):133–135.

Source of support: Nil

Conflict of interest: None

Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.

INTRODUCTION

Toluene, an aromatic hydrocarbon is frequently used in paints, varnishes, glues, and industrial solvents. Being a commonly abused drug, it is known to cause intense euphoria followed by neurological depression. Intoxication can be environmental, accidental, or intentional via inhalational, enteral, or dermal routes.1,2 Acute toluene intoxication is typically characterized by hyperchloremic metabolic acidosis with inappropriate urinary potassium excretion. Excess excretion of benzoic and hippuric acids can lead to raised anion gap metabolic acidosis. Toluene exposure can also lead to acute kidney injury (AKI) due to muscular injury and rhabdomyolysis.3 Patients usually present with severe neuromuscular weakness due to severe hypokalemia, which can result in life-threatening respiratory failure. Severe hypokalemia may precipitate ventricular arrhythmias due to prolongation of QTc interval.4 It can also be accompanied by proteinuria, excess excretion of phosphate, and Fanconi’s syndrome. Delay in diagnosis and management can prove to be fatal, with mortality rate of up to 15%.1 A confirmatory diagnosis is made by demonstrating the presence of hippuric acid in urine.

Our case report highlights accidental toluene intoxication as an important cause of hyperchloremic metabolic acidosis with hypokalemia and neurological compromise.

CASE DESCRIPTION

A 30-year-old unconscious female patient was rushed to the casualty by relatives with chief complaints of generalized muscular weakness and altered breathing pattern with drooling of saliva followed by a drop in consciousness for the past 4 hours. Muscular weakness was sudden in onset, ascending in nature, and was rapidly progressive. The patient’s husband provided a history of frequent glue and varnish sniffing, with occasional ingestion of whitener solution for the past 5 to 6 months. No psychiatric consultation had been sought for the same. There were no previous hospitalizations with similar complaints. When examined, the Glasgow Coma Scale (GCS) score was 3 (E1V1M1), with dilated and sluggishly reacting pupils. A distinct fruity odor was emanating from the patient’s mouth. The patient was hemodynamically stable throughout her stay in casualty. Intravenous access was secured, and point-of-care investigations and arterial blood gas (ABG) analysis were sent. A note was made of hesitation cut marks on the left forearm (Fig. 1).

Fig. 1: Self-inflicted hesitation marks on our patient’s forearm, possibly signifying previous suicidal attempts

Airway management took precedence, and the trachea was intubated with cuffed endotracheal tube #7.5 mm. On auscultation, coarse crepitations were present on the right side, suggesting possible aspiration. A forensic medicine consultation was sought for possible acute toluene intoxication, which advised against gastric lavage. Patient’s 12-lead electrocardiogram (ECG) revealed prolongation of corrected QT (QTc) interval to 556 MS with ST depression and T-wave inversion. The chest X-ray and computed tomography of the head were normal. Blood investigations showed hemoglobin concentration of 11.4 g/dL, white cell count of 11,700 cells/mm3, serum sodium 125 mEq/L, serum potassium 1.7 mEq/L, serum magnesium 0.8 mg/dL, blood urea 54 mg/dL, serum creatinine 0.6 mg/dL, and normal liver function tests. ABG analysis revealed severe metabolic acidosis [pH = 6.78, arterial partial pressure of carbon dioxide (PaCO2) = 47.1, bicarbonate (HCO3) = 6.4, arterial partial pressure of oxygen (PaO2) = 102, lactate = 3.6 on fraction of inspired oxygen (FiO2) of 0.5] with normal anion gap. The patient was thereafter transferred to the intensive care unit (ICU) for mechanical ventilation and further correction of metabolic parameters.

In the ICU, internal jugular central venous access was secured, and crystalloid infusion (around 3 L in the first 24 hours) was started. Acidosis correction was started with a bolus of inj. sodium bicarbonate 150 mEq over 2 to 3 hours followed by 20 mEq/h infusion for 24 hours via a central line with ABG monitoring. Potassium replacement was started at the rate of 40 mEq/h (total 600 mEq replacement in 24 hours). A bolus dose of 4 gm of magnesium was given followed by 500 mg/h infusion for 8 hours, making a total of 8 gm of magnesium. Frequent ABG analyses as well as blood and urine biochemistry were performed during her ICU stay (Tables 1 and 2). The patient had inappropriate kaliuresis as demonstrated by the calculated transtubular potassium gradient (TTKG) of over 7 (normal < 3). After the first 24 hours, serum lactate normalized to 1.5 mmol/L, and acid–base abnormalities showed an improving trend. However, serum creatinine increased to 1.4 mg/dL [Kidney Disease Improving Global Outcomes (KDIGO) stage 2—AKI]. This, however, improved spontaneously over the next few days. By day 3 of ICU stay, the patient’s GCS recovered fully, and she was conscious and obeying commands. Trachea was extubated, and by day 4, muscle power in all four limbs had recovered completely (5/5). Oral intake was started. A psychiatry consultation was sought for the patient, following which the patient was transferred out of ICU.

Table 1: Arterial blood gases, serum electrolytes, and laboratory investigations during the first 24 hours measured sequentially
0 hour 6 hours 12 hours 18 hours 24 hours
pH 6.82 7.05 7.13 7.27 7.39
PaCO2 (mm Hg) 39 32.4 31.8 33.6 31.6
HCO3 (mmol/L) 9.8 10.4 11.4 14.6 19.8
Na+ (mmol/L) 125 129 132 135 138
K+ (mmol/L) 1.7 2.2 2.5 2.6 2.8
Mg2+ (mg/dL) 0.8 1.0 2.2
Hb (g/dL) 10.9 10.7
TLC (/mm3) 5500 6000
Platelet (lakh/mm3) 2.44 1.98
Urea (mg/dL) 46 44
Creatinine (mg/dL) 0.7 0.8

Hb: hemoglobin; HCO3: bicarbonate; K: potassium; Mg: magnesium; Na: sodium; PaCO2: arterial partial pressure of carbon dioxide; TLC: total leukocyte count

Table 2: Specialized investigations performed on day 1 of ICU stay. Simultaneous plasma and urine potassium values are required to determine whether kaliuresis is occurring and is causing hypokalemia
Special investigations At 24 hours
S. CPK (U/L) 129
Procalcitonin (ng/mL) 5.6
NT-proBNP (pg/mL) 4698
Plasma osmolality (mOsm/L) 280
Urine osmolality (mOsm/L) 582
Urine pH 6.5
Urine potassium (mmol/L) 26
Urine sodium (mmol/L) 42
Urine creatinine (mg/dL) 13.6

CPK: creatine phosphokinase; NT-proBNP: N-terminal pro b-type natriuretic peptide

DISCUSSION

Toluene intoxication most commonly presents with severe hypokalemia-induced rapidly progressive, ascending neuromuscular paralysis, occasionally resulting in respiratory compromise.1,2 This is accompanied by distal renal tubular acidosis (RTA) type I (traditionally a hyperchloremic metabolic acidosis with hypokalemia) and AKI. Toluene-induced distal RTA type I is characterized by an inability to reduce urinary pH despite severe acidemia because of a reduced ability of the distal tubule to excrete hydrogen ions as ammonium. This is accompanied by an overproduction of hippuric acid by toluene metabolism.1,5

Transtubular potassium gradient is calculated to demonstrate inappropriate excretion of potassium in urine or kaliuresis.6

Where,

UK is urine potassium concentration.

PK is plasma potassium concentration.

Uosm is urine osmolality.

Posm is plasma osmolality.

Our patient had an increased TTKG value of 7.59 (normally <3), suggestive of excess potassium release in urine. We also calculated urine potassium to serum creatinine ratio in our patient (UK/UCr = 26/13.6 = 1.9), which was above a cutoff value of 1.5, suggesting excessive potassium excretion in urine.7 This highlights the importance of measuring urine electrolytes in the management of a patient with severe hypokalemia and gives a clue regarding the etiology.

Both glomerular and tubular damage have been associated with toluene intoxication, causing acute oliguric renal failure and at times progressing to end-stage renal disease. This is associated with an adverse patient outcome. Rhabdomyolysis is another cause of tubular injury and renal failure in toluene poisoning.3 Dyselectrolytemias such as hypokalemia (especially when serum potassium levels are <2.0 mmol/L) as well as hypophosphatemia are known to result in rhabdomyolysis.8

Cardiac manifestation such as acute myocardial infarction, as well as arrhythmia and ST-T segment changes related to hypokalemia may be observed in these patients.3 Chronic toluene abusers also exhibit longer QT and QTc intervals compared to normal population. The primary cause of death in acute intoxication is commonly cardiac arrhythmias. Severe acidosis also results in refractory cardiac arrest.4

Management of a patient of acute toluene toxicity starts with airway control, oxygenation, ventilation, and circulatory support. Gastric lavage is usually not indicated, and there is no specific antidote. Patients may preferentially be admitted to ICU, and frequently a multidisciplinary input is essential for successful recovery. Treatment usually involves hydration, aggressive correction of electrolyte and acid–base abnormalities under close monitoring of the cardiac rhythm. Early placement of a central venous catheter may be essential for adequate potassium replacement. Rhabdomyolysis should be suspected and looked for. Acute oliguric renal failure should be recognized and treated early, and in case of nonreversal, renal replacement therapy might be promptly considered. Cardiac evaluation and monitoring are equally important and may require a cardiologist input. After stabilization, special attention should be given to institute future preventive measures, including psychiatry consultation, patient education, rehabilitation, and follow-up.1

CONCLUSION AND CLINICAL SIGNIFICANCE

Toluene is a common drug of abuse, and patients with acute toluene intoxication may present to casualty. These patients present with generalized weakness, reduced consciousness, acid–base imbalance, and severe electrolyte disturbances. They may also progress to develop AKI with or without rhabdomyolysis. The hallmark pathology is hyperchloremic metabolic acidosis with severe hypokalemia (distal RTA type I). Such patients benefit from an early ICU admission, appropriate fluid therapy to prevent AKI, and aggressive management of acid–base and electrolyte abnormalities.

AUTHORS’ CONTRIBUTION

Gursharan Singh: Patient management, manuscript preparation; Aman Shukla: Patient management; Priyanka H Chhabra: Patient management; Santvana Kohli: Manuscript preparation and review.

ORCID

Gursharan Singh https://orcid.org/0000-0002-2413-4535

Aman Shukla https://orcid.org/0009-0005-2434-7564

Priyanka H Chhabra https://orcid.org/0000-0001-9436-6123

Santvana Kohli https://orcid.org/0000-0003-1410-6933

REFERENCES

1. Camara-Lemarroy CR, Rodriguez-Gutierrez R, Monreal-Robles R, et al. Acute toluene intoxication—clinical presentation, management and prognosis: a prospective observational study. BMC Emerg Med 2015;15:19. DOI: 10.1186/s12873-015-0039-0

2. Taher SM, Anderson RJ, McCartney R, et al. Renal tubular acidosis associated with toluene “sniffing”. N Engl J Med 1974;290(14):765–768. DOI: 10.1056/NEJM197404042901403

3. Streicher HZ, Gabow PA, Moss AH, et al. Syndromes of toluene sniffing in adults. Ann Intern Med 1981;94(6):758–762. DOI: 10.7326/0003-4819-94-6-758

4. Carder JR, Fuerst RS. Myocardial infarction after toluene inhalation. Pediatr Emerg Care 1997;13(2):117–119. DOI: 10.1097/00006565-199704000-00009

5. Carlisle EJ, Donnelly SM, Vasuvattakul S, et al. Glue-sniffing and distal renal tubular acidosis: sticking to the facts. J Am Soc Nephrol 1991;1(8):1019–1027. DOI: 10.1681/ASN.V181019

6. Lin SH, L in YF, Chen DT, et al. Laboratory tests to determine the cause of hypokalemia and paralysis. Arch Intern Med 2004;164(14):1561–1566. DOI: 10.1001/archinte.164.14.1561

7. Groeneveld JH, Sijpkens YW, L in SH, et al. An approach to the patient with severe hypokalemia: the potassium quiz. QJM 2005;98(4):305–316. DOI: 10.1093/qjmed/hci046

8. Knochel JP, Schlein EM. On the mechanism of rhabdomyolysis in potassium depletion. J Clin Invest 1972;51(7):1750–1758. DOI: 10.1172/JCI106976

________________________
© The Author(s). 2024 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.