Lung injury and renal failure caused by potassium cyanide poisoning

Abstract

Our objective is to show that cyanide poisoning presents with various symptoms, and that recognition of these symptoms is required for appropriate management of the condition. A 54-year-old man drank about 2.5 times the normal fatal dose of potassium cyanide in a suicide attempt. On arrival at hospital (day 0), the patient was restless and in a state of shock. We administered 100% oxygen and performed immediate detoxification. Ground-glass attenuation appeared on the evening of day 1 and lung injury due to cyanide was suspected. Inflammation improved slowly with the use of artificial ventilation, but anuria continued and sudden renal failure occurred on day 2. We suspected that renal failure was due to cyanide metabolites, and continuous haemodiafiltration (CHDF) was initiated. Renal function improved slowly and CHDF was discontinued on the sixth day. Symptoms of cyanide poisoning may include lung injury and renal damage, in addition to disturbance of consciousness.

Background

Cyanide is used for chemical synthesis, plating and metalwork.¹ The rapid reactivity and high toxicity of cyanide has made it a compound of choice for suicide and murder for many years. Treatment of cyanide poisoning is difficult due to the immediacy of the effect, but modern emergency medicine is changing this situation. In the case reported here, the patient ingested about 2.5 times the normal fatal dose of potassium cyanide and developed acute lung injury and renal failure, but recovered following intensive care. This case is of interest since cyanide poisoning is rare and information on the extended clinical course of this condition is limited.

Case presentation

A 54-year-old man with no hospital history mixed potassium cyanide (0.5 g) with coffee (100 ml) and drank this mixture in an attempt to commit suicide at 22:00 h. Frequent vomiting, diarrhoea and a feeling of illness developed 2 h later and his family noticed these changes at 8:00 h the next morning (day 0) and requested an ambulance. On arrival, the patient was restless and his Glasgow Coma Scale was E(3) V(4) M(6). His vital signs were blood pressure 75/50 mm Hg, pulse 120/min (tachycardia) and respiratory rate 30/min. The radial artery was not palpable and limbs were cold.

Investigations

Blood gas analysis revealed pH 7.44, pco₂ 24.3 mm Hg, po₂ 78 mm Hg (O₂ 10-litre reservoir mask, Fio₂ 1.0), K⁺ 3.3 mmol/l (normal, 3.7–4.8 mmol/l), Na⁺ 141 mmol/l (normal, 140 mmol/l), Ca²⁺ 1.10 mmol/l (normal, 8.8–10.2 mmol/l), Cl^– 106 mmol/l (normal, 98–108 mmol/l), lactate 144 mg/dl (normal, 4–15 mg/dl) and anion gap 18.5 mEq/l (normal, 12±4 mEq/l). Laboratory tests revealed BUN 17 mg/dl (normal, 8–22 mg/dl), creatinine 1.81 mg/dl (normal, 0.6–1.10 mg/dl), AST 102 U/l (normal, 13–33 U/l), ALT 50 U/l (normal, 6–30 U/l), C-reactive protein 0.56 mg/dl (normal, <0.1 mg/dl), LDH 536 U/l (normal, 119–229 U/l), white blood cell count 25010/μl (normal, 3500–9000/μl) and neutrophils 90% (normal, 40–70%).

Treatment

The patient showed disturbed consciousness, tachycardia and low blood pressure, and was treated with 100% oxygen, sodium bicarbonate for acidosis, and sodium nitrite 300 mg and sodium thiosulfate 14 g for immediate detoxification. This treatment was repeated 6 h later. Activated carbon 50 g was administered and the digestive organs were decontaminated with laxative 7 h after admission.

Outcome and follow-up

Hypovolemic shock and lung oedema

Thirst and cold limbs were apparent on arrival (day 0) and the patient was dehydrated with Hb 19.7 mg/dl. Blood pressure was maintained at 70 mm Hg by means of a large infusion while dopamine 10 μg/kg/min and noradrenaline 0.05 μg/kg/min were administered. Intravenous fluids totalling 9500 ml were given over the 24 h after arrival, but inferior vena cava diameter collapse persisted and the volume of urine was also insufficient. Body weight had increased by 5.5 kg on the morning of day 2, and bilateral pleural effusion was apparent in a chest radiograph with lung oedema evident on echography. We attempted to maintain respiration with a non-invasive positive pressure ventilation mask, but endotracheal intubation was required because Spo2 deteriorated to below 90%.

Lung injury caused by cyanide

The white blood cell count had increased to 20 300/μl by the morning of day 1 and consolidation appeared in the left middle lung field, which had not been detected on a chest radiograph on day 0. Ground-glass attenuation appeared in both lung fields on the evening of day 1 (figure 1) and body temperature rose to 38.5°C. Lung injury due to cyanide poisoning was suspected because the progression was rapid and specific bacteria were not detected in blood culture or sputum culture. The inflammation improved slowly as the patient continued under artificial ventilation. Consolidation in both lung fields had almost resolved on chest radiograph on day 7 and the patient was extubated since breathing was stable.

Figure 1.

(A) Chest radiograph after hospital arrival showing no abnormality in the lung fields. (B) Left lung consolidation appeared 34 h after the patient took potassium cyanide. (C) Bilateral consolidation appeared after 40 h.

Acute renal failure caused by cyanide

A large volume of intravenous fluid was given for shock, but anuria continued and sudden renal failure developed on day 2 with BUN 76 mg/dl and Cr 4.33 mg/dl. Since progression was rapid, we suspected renal damage due to cyanide metabolites and started continuous haemodiafiltration (CHDF) to promote excretion of cyanide.² Renal function improved slowly and urine increased gradually during fluid removal by CHDF. CHDF was discontinued on day 6, after which renal function improved rapidly and the patient was discharged from the ICU on day 15.

Discussion

Cyanide poisoning should be suspected in cases with significant unexplained metabolic acidosis and rapid development of disturbed consciousness, or cases without cyanoses but with respiratory depression (tachypnoea), and the detailed medical history should be checked.³ In our case, the family discovered cyanide beside the patient who worked in a factory that used organic solvents, which allowed easy diagnosis of cyanide poisoning.^4,5

The fatal oral dose of potassium cyanide in adults is 200–300 mg and this dose is absorbed in a few minutes.^6,7 A lack of instrumentation in our hospital prevented measurement of the cyanide concentration in blood. However, in patients with a clinical history consistent with cyanide poisoning, the plasma lactate concentration has been found to correlate with the blood cyanide concentration before antidote treatment⁸ and in our patient the plasma lactate value was consistent with a fatal dose of cyanide. The basis of cyanide toxicity is thought to be inhibition of activation of cytochrome C oxidase (COX), which is the final mitochondrial membrane enzyme involved in the transfer of an electron to oxygen from an electron donor generated in the TCA cycle. This inhibitory action decreases energy production by blocking ATP production through oxidative phosphorylation, which then leads to brain and heart damage. Concrete symptoms include dizziness, unsteadiness, tachypnoea, a feeling of nausea, vomiting, reduced consciousness, and restlessness. Tachycardia, bradycardia, arrhythmia and a fall in blood pressure occur as ATP is produced through anaerobic glycolysis, and significant metabolic acidosis occurs due to accumulation of lactic acid in the blood. Cyanide poisoning may also cause respiratory symptoms of bronchitis, lung oedema and pneumonia, and digestive symptoms of vomiting and stomach pain.^5,9

In our patient, lung injury and renal damage occurred in addition to disturbed consciousness.¹⁰ Potassium cyanide reacts with gastric acid and generates hydrogen cyanide gas, which has a particularly early toxic effect since it is absorbed rapidly by the lungs and skin.^1,2 In our case, left lung consolidation appeared 34 h after taking potassium cyanide and bilateral consolidation was evident at 40 h. There have been no previous descriptions of the course of lung injury caused by cyanide, but in this case the lung injury was reversible and consolidation improved gradually during artificial respiration. In addition, renal damage suddenly appeared on day 2 after taking cyanide. This may have been due to cyanide metabolites and resolved rapidly following CHDF for promotion of excretion of cyanide. Renal failure caused by cyanide can be fatal and CHDF may be a useful approach after detoxification with 100% oxygen, which reactivates mitochondrial enzyme activity and is thought to enhance the effect of the antidote (thiosulfate).^2,9

Cyanide detoxification can be achieved through three pathways: dissociation of CN⁻ from COX by methaemoglobin and thiocyanate; CN⁻ uptake by hydroxocobalamin (vitamin B12a) with conversion to cyanocobalamin (vitamin B12); and chelation by cobalt (Co₂EDTA). The first of these pathways takes advantage of the interaction of CN⁻ with trivalent Fe^III for detoxification through the following mechanism. Iron in haemoglobin is bivalent (Fe²⁺) and is oxidised by nitrous acid (nitrite administration) to Fe³⁺; that is, haemoglobin is converted to methaemoglobin. Methaemoglobin binds to CN⁻ to form cyanomethaemoglobin and displaces CN⁻ from COX. However, this pathway also causes haemoglobin to lose its oxygen-binding capacity and less than 30% of the total haemoglobin should be converted to methaemoglobin. CN⁻ gradually dissociates from cyanomethaemoglobin and is converted to thiocyanate through a reaction with thiosulfuric acid (catalysed by rhodanese) and excreted from the kidney.

In our patient, the methaemoglobin level rose to 6.4% after antidote administration, indicating the effectiveness of the treatment. For acute cyanide poisoning, administration of 100% oxygen and antidote immediately after arrival at hospital improves outcome and may be life-saving.^11,12 Our patient took about 2.5 times the dose of potassium cyanide that is thought to be fatal, but was saved by these procedures and subsequent intensive care.

The course included lung injury and renal failure, in addition to disturbed consciousness, and recognition of these symptoms is of importance in cases with suspected cyanide poisoning.

Learning points

• Early administration of an antidote with 100% oxygen may result in improved outcome in a case of cyanide poisoning.

• The course of cyanide poisoning may include lung injury and renal failure, in addition to disturbed consciousness.

• Cyanide poisoning presents with various symptoms, and recognition of these symptoms allows for appropriate management of this condition in an intensive care unit.