N-acetylcysteine infusion in preventing hepatotoxicity secondary to intravenous injection of household bleach

Abstract

We present a case of non-accidental injection of 40 ml of domestic bleach through a long-term central venous catheter (CVC) with subsequent AKI, and for the first time in the literature severe coagulopathy and acute liver injury. We detail the clinical course of events and our management plan which adds to the body of evidence for prognosis and treatment in these unusual cases.

Introduction

Sodium hypochlorite (NaOCl) based bleach solutions are widely available to the general public for domestic use in addition to their use in industry. Accidental exposure and intentional abuse by a variety of routes including ingestion, inhalation of vapour, topical application and intravenous injection have been reported in the literature.^1,2 Most instances reported have resulted in minor or transient damage without permanent consequence. However, there are also several reports of permanent damage and even some of death.¹ With particular reference to the intravenous route, there is a paucity of literature detailing serious complications following injection. There are case reports detailing local pain, oedema, thrombosis and acute kidney injury (AKI).^2–5

Presentation

A 54-year-old woman presented to the emergency department 1 h after injecting 40 ml of domestic bleach through a long-term CVC (Hickman line). She had sought medical assistance only after having noticed the development of bruises over her abdomen, in addition to dark coloured urine. Her past medical history was particularly notable for severe depression and episodes of self-harm. In a previous admission she presented having ingested a large quantity of bleach, ultimately resulting in significant small bowel resection and leaving her with short bowel syndrome. As a result she had a left subclavian vein Hickman line sited for long-term nutritional support, which she used for intravenous access during this current episode of self-harm.

Progress

On admission, the patient was fully conscious with vital observations within acceptable limits. Her heart rate was 79 bpm in sinus rhythm, with a blood pressure of 152/101 mmHg. Her respiratory rate was 17/min and oxygen saturations 100% on room air. Physical examination was only remarkable for abdominal wall bruising and the presence of a Hickman line in her left subclavian vein. Initial management consisted of fluid therapy with 1 l of normal saline and blood sampling for routine biochemistry, haematology and clotting studies. She was transferred to the acute medical admissions unit for further assessment and monitoring.

It became apparent over a time period of approximately 6 h that she was developing a large haematoma over her antecubital fossa at the site of blood sampling, and despite fluid resuscitation with a further 2 l of normal saline had become anuric. On discussion with the biochemical and haematological laboratories it became evident that further electrolyte and haematological analyses were proving technically impossible as a result of severe haemolysis and incoagulability. Further toxicology screening to rule out mixed overdose was not possible due to the severity of the haemolysis, but further history taking from the patient and her family revealed no evidence of any other substance overdose. Despite this deterioration her vital signs remained within normal values; however, the decision was made to admit her to the intensive care unit (ICU) for supportive therapy and consideration of continuous veno-venous haemofiltration (CVVHF).

The patient’s unmeasurable international normalised ratio (INR) and an initial thromboelastogram which showed a flat line, suggested a complete lack of fibrin clot formation. We therefore made the decision to transfuse a combination of 4 g of fibrinogen, 4 units of fresh frozen plasma and 10 mg of intravenous Vitamin K. In conjunction with correction of her coagulopathy, a femoral vascular access dialysis catheter and a femoral CVC were inserted with extreme caution under ultrasound scan guidance. CVVHF was commenced using citrate-calcium regional anticoagulation, using a standard weight-based protocol.⁶ Aggressive intravenous fluid hydration with normal saline at a rate of 250 ml/h was also initiated. We performed a literature search of bleach-induced kidney injury, suggestive that oxidative damage is thought to play a significant role in its pathogenesis.^4,5 We commenced an infusion of N-acetylcysteine to counteract any further damage and to pre-emptively treat, by extrapolation of oxidative injury to other systems, possible hepatotoxicity. We used, as a default, a dose similar to that used in paracetamol-induced hepatotoxicity⁷ (first dose: 150 mg/kg over 1 h, second dose: 50 mg/kg over 4 h, third dose: 100 mg/kg over 16 h, and further infusions at 100 mg/h for the remainder of the duration). The NAC infusion was continued for the duration of her ICU stay. The patient did not require respiratory or cardiovascular system support during her ICU admission.

When her blood chemistry became analysable (14 h after admission) these confirmed AKI and acute liver injury in addition to a coagulopathy. The blood tests showed a doubling of her baseline creatinine to 119 µmol/l, urea of 13 mmol/l, sodium 144 mmol/l, potassium 3.8 mmol/l. Her initial ALT was raised at 80 iu/l, with a bilirubin of 81 µmol/l and Alk Phos 263 iu/l. Haematology and clotting studies revealed an INR of 1.4, PT 15 s, APPT ratio 1.5, fibrinogen 0.8 g/l, haemoglobin 92 g/l and platelets of 208 × 10⁹/l. Despite the severity of the haemolysis and biochemical derangement, over the course of the next 24 h her urine output improved to an average of greater than 0.5 ml/kg/h. In addition, her acidosis corrected to normal values and therefore CVVHF was discontinued. Following administration of clotting products, her coagulopathy also rapidly improved without any residual derangement. Her liver function test (LFT) derangements in contrast to her other biochemical markers continued to deteriorate, peaking on day four of her hospital admission with values of ALT 553 iu/l, Alk Phos 1040 iu/l, bilirubin 172 µmol/l. They had previously been within normal limits six weeks prior to admission.

Two days later she was de-escalated to the acute medical ward as no organ support was required. Following a review by the acute liaison psychiatry team, she was deemed fit for discharge home several days later, with an outpatient appointment arranged for repeat LFTs and a liver ultrasound scan one week later. The follow-up outpatient liver ultrasound scan and blood tests were unremarkable and she had therefore suffered no permanent sequelae from this episode.

Discussion

The postulated mechanism of cell damage or death by sodium hypochlorite involves the generation of superoxide radicals and subsequent oxidative injury. These radicals form when sodium hypochlorite, a strong alkali (pH ∼ 11), forms hypochlorous acid (HOCl) on contact with water-based solutions and account for its use as a household disinfectant.⁴

There was one similar case report detailing the injection of 100 ml of bleach by tunnelled line intravenously. The patient developed AKI, transient haemolysis and mild coagulopathy. Prothrombin time and activated partial thromboplastin time were 28.5 (9.6–12.5) and 46 (22.3–34) s, respectively. That case was treated with intravenous fluid therapy and haemodialysis.⁴

Because of its disinfectant properties sodium hypochlorite-based solutions were used by intravenous drug abusers to sterilise syringes, particularly to kill the human immunodeficiency virus. It was by this mechanism that two case reports detailing the injection of less than 1 ml of bleach causing pain and vomiting exist.² By and large, the injection of small volumes of bleach appears relatively safe.⁸ For the same reasons, sodium hypochlorite solutions are the most widespread irrigation solution used in dentistry during root canal procedures as a disinfectant. It is very effective in killing the bacteria and other pathogens to prepare the root canal before the filling. There are few case reports of inadvertent injection of small volumes of the solution into the periapical tissues causing local tissue damage and severe tissue necrosis.^9,10 There are two case reports involving a more significant volume of injection including 20 ml causing pain, oedema and superficial vein thrombosis³ and 100 ml causing haemolysis and AKI.⁴

In our case the predominant physiological disturbances were haemolysis, acute renal failure, coagulopathy and acute liver failure. Haemolysis is thought to occur by oxidative injury when sodium hypochlorite comes into contact with plasma in addition to the protein degradation effects of the hypertonic solution. As a result nephrotoxic haem breakdown products are released, compounding kidney injury from direct toxicity (probably oxidative damage to the renal tubular epithelium⁵), rhabdomyolysis, hypotension and volume depletion.^4,5 We postulate that the acute liver injury suffered was of a similar nature to the renal insults, with oxidative injury playing an important role and other systemic factors as mentioned earlier compounding these effects. As for the coagulopathy, its rapid reversal with clotting products does hint at a similar mechanism to the haemolysis detailed earlier.

In another case involving similar volumes of intravenous bleach, it was interesting to note the similarities in sequence and timing of events. Black urine was one of the early presenting features also occurring within hours of injection,⁴ anuria developed in each instance despite fluid resuscitation over a period of 6–8 h from injection and blood became analysable 12–14 h after injection. Furthermore, renal impairment which required renal support resolved over a period of days. In each instance despite markedly deranged biochemistry, there were no permanent sequelae, with improvements over a period of days.

TOXBASE® recommendations for the treatment of intravenous bleach do not exist, and there is certainly no well recognised antidote. Supportive care should therefore be the mainstay of treatment with fluid resuscitation being at the forefront to prevent ischaemic injury and increase in renal tubular flow. Specific therapies from other cases include bicarbonate infusion to prevent the precipitation of haem casts and decrease in the production of free iron from myoglobin in rhabdomyolysis,⁴ and sodium thiosulphate acting as a reducing agent for neutralising NaoCL.¹¹ However, it is important to note that these therapies are not evidence based.⁴ Exchange transfusion has also been mentioned as a means of ameliorating haemolysis but again there is no record of this being performed. The role of dialysis is largely limited to supportive care; however, the sodium hypochlorite molecule by virtue of its small molecular weight and low volume of distribution should be dialyzable.^4,5 As the toxic effects are likely to occur upon contact with plasma, the role of dialysis in preventing direct harm may well be limited.

We instituted an infusion of N-acetylcysteine on the basis that this would theoretically help to prevent further oxidative injury of which we were conscious, having read of the mechanism of injury of bleach. N-acetylcysteine has multiple uses in medicine with varying levels of evidence supporting its efficacy with the management of paracetamol toxicity probably being the most popular and proven. Most of these clinical applications stem from its theoretical ability to support the body’s antioxidant and nitric oxide systems during stress, infections, toxic assault and inflammatory conditions. This is predominantly through the increase of glutathione the body’s major antioxidant that exerts a profound protective effect on cells.¹² Internal and external toxic insults can rapidly deplete glutathione reservoirs, which if not replaced may result in severe damage or even cell death. NAC to a lesser extent also exhibits a direct antioxidant action in which its thiol group combines with reactive oxidant species to form a harmless compound.¹² We instituted the N-acetylcysteine infusion for the duration of her ICU stay (48 h in total) and at this point with evidence of normalising liver synthetic function and clinical improvement we decided to stop it. In the future we would be more inclined to perform this earlier on to attempt to prevent or at least dampen renal impairment and other oxidative injury. We do however understand that there is only at present theoretical benefit from this.

On the basis of this and other similar cases, it appears that intravenous injection of sodium hypochlorate-based solutions carry a reasonable prognosis despite wide ranging systemic and biochemically severe effects. Interestingly, the two cases of large volume injection caused similar effects over similar time periods. On the basis of this, we would advocate aggressive fluid resuscitation in a critical care area on presentation in addition to preparation for renal supportive therapies. Blood and coagulation product replacement, and early institution on N-acetylcysteine infusions would also form part of our management recommendations.

Consent

Written consent for publication was provided by the patient.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.