Case report
Fatal methaemoglobinaemia in a dental nurse. A case of sodium nitrite poisoning W J GOWANS SUMMARY Methaemoglobinaemia may be caused by ingestion of a number of drugs, among them nitrites, some of which are remarkably toxic. This was tragically highlighted by the death of a 17 year old dental nurse after taking a single 1 g tablet of sodium nitrite. These tablets are widely used in the medical and dental profession to prevent rusting of instruments while immersed in disinfectant solutions. The toxicity of this chemical should be more widely recognized and its storage made correspondingly more secure. Methaemoglobinaemia should be considered as a diagnosis in any patient with significant central cyanosis in whom there is no obvious cardiorespiratory cause.
Case history M ISS H, a 17 year old dental nurse, was admitted to the casualty department at 18.30 hours after being found at home in an hysterical condition and bright blue. On admission she had central cyanosis, tachycardia and tachypnoea. Her chest was clear and she had a systolic blood pressure of 90 mmHg. No history was obtainable from her but her boyfriend reported that she had been fit and well earlier in the day and that he had not seen any evidence of drug ingestion at her house. Fifteen minutes after admission she vomited, aspirated and suffered a respiratory arrest. She was intubated and ventilated. Despite her cyanosis her arterial blood gases were normal. Apart from recent aspiration there was no other indication that her cyanosis was of cardiorespiratory origin. A venous blood sample was noted to be chocolate brown in colour. Methaemoglobinaemia was suspected and spectroscopy of a blood sample confirmed 'severe methaemoglobinaemia'. Forty five minutes after admission, methylene blue was administered intravenously (2 mg kg-' over 10 minutes). However, by 19.30 hours her blood pressure was unrecordable, a series of cardiac arrythmias ensued and, despite the insertion of a temporary pacing wire together with standard resuscitation measures, she failed to recover. She was certified dead at 20.30 hours, two hours after admission. Postmortem findings confirmed a normal cardiorespiratory system apart from evidence of minor aspiration into the upper lobe of the right lung. Biochemical analysis after death revealed that the level of methaemoglobinaemia was 35%, implying a much higher level on admission to hospital. The serum nitrite ion level was 13 mg 1-'. This level is consistent with death from nitrite poisoning following the ingestion of a single 1 g tablet of sodium nitrite.
Discussion The haemoglobin molecule is made up of four haem molecules each of which contains one iron atom in the Fe(II) state. Methaemoglobinaemia is caused by oxidation of one or more of the iron atoms to the Fe(III) state. Oxidation of a single haem changes the conformation of the haemoglobin molecule such W J Gowans, MRCP, MRCGP, medical registrar, Watford General Hospital. Submitted: 14 November 1989; accepted: 26 June 1990.
© British Journal qf General Practice, 1990, 40, 470-471.
470
that the oxygen affinity of the remaining three haem molecules is increased. The oxygen dissociation curve of methaemoglobin is shifted to the left compared with that for haemoglobin, resulting in impaired oxygen unloading to the tissues. The clinical effect of 30% methaemoglobinaemia is therefore much greater than an equivalent reduction in haemoglobin level. In more severe cases of acquired methaemoglobinaemia a haemolytic anaemia may ensue. A characteristic feature of methaemoglobinaemia is the chocolate brown appearance of whole blood which is said to be present at methaemoglobin concentrations as low as 15-20%. Acquired methaemoglobinaemia is caused by ingestion of or exposure to various oxidant drugs or chemicals. Chronic exposure to a low dose of oxidant may produce minimal methaemoglobinaemia and no symptoms whereas the acute ingestion of the same total dosage may be lethal. Treatment of chronic acquired methaemoglobinaemia involves withdrawal of the offending drug or chemical. If continued therapy is indicated then the dose of oxidant to which the patient is exposed should be reduced. Acute methaemoglobinaemia, if life threatening, should be treated with oxygen and intravenous methylene blue; both reduce levels of methaemoglobin. If there is intravascular haemolysis then plasmapheresis or exchange transfusion is indicated. The list of drugs which cause methaemoglobinaemia is long. It includes organic and inorganic nitrites, nitrates, local anaesthetics, dapsone, aniline dyes and sodium chlorate. Numerous cases of infant methaemoglobinaemia have resulted from consumption of rural well water high in nitrates which are converted into nitrites in the gut. Amyl or butyl nitrite is often abused as an inhalation intoxicant and to heighten orgasm and several cases of severe poisoning and deaths have been reported. 1-5 Serum nitrite levels in cases where death has followed accidental or intentional ingestion of sodium or potassium nitrite have varied from 0.5 to 340 mg 1-1.67 Serum nitrite levels vary widely between individuals who have ingested roughly equivalent doses of the same nitrite preparation. There are several reported cases of fatal sodium or potassium nitrite overdose in which the chemical has been identified in gastric contents but not in other body fluids or tissues.8-'2 The correlation between serum methaemoglobin concentrations and symptoms is more consistent. Cyanosis is detectable at serum methaemoglobin concentrations of 15%, 407o causes severe headache with weakness and ataxia while levels above 70% will cause severe cyanosis, tachycardia and dyspnoea with the risk of cardiovascular collapse and death.'3 Sodium nitrite tablets (1 g) are supplied as an adjunct to disinfectant fluids such as chlorhexidine. When dissolved in the fluid sodium nitrite acts as a strong oxidizing agent preventing rusting of the instruments being disinfected. The label on a sodium nitrite container indicates that the material is toxic by ingestion both in text and using the standard symbol of a skull and crossbones in black on an orange background. In the case just cited the dental nurse almost certainly obtained the tablet(s) from the practice in which she was employed. They were routinely left by the side of the disinfectant bath in which they were used. Furthermore, she probably took only one tablet; this being enough to produce a serum nitrite level that was lethal despite active treatment. The toxicity of sodium nitrite
British Journal of General Practice, November 1990
Case report
W J Gowans tablets is not widely known, despite their widespread use in the medical and dental professionis. If they are to be kept on surgery premises at all then secure storage must be guaranteed. This case serves to remind general practitioners to consider methaemoglobinaemia as a diagnosis in any patient with significant central cyanosis in whom there is no obvious cardiorespiratory cause.
References 1. Smith M, Stair T, Rolmick MA. Butyl nitrite and a suicide attempt. Ann Intern Med 1980; 92: 719. 2. Shesser R, Mitchell J, Edelstein S. Methaemoglobinaemia from isobutyl nitrite preparation. Ann Emerg Med 1981; 10: 262. 3. Home MK, Waterman MR, Simon LM, et al. Methaemoglobinaemia from sniffing butyl nitrite. Ann Intern Med 1979; 91: 417. 4. Shesser R, Dixon D, Allen Y, et al. Fatal methaemoglobinaemia from butyl nitrite ingestion. Ann Intern Med 1980; 92: 131. 5. Wason S, Detsky AS, Platt OS, Lovejoy FH. Isobutyl nitrite toxicity by ingestion. Ann Intern Med 1980; 92: 637.
6. Naidu S, Rao P. Case of nitrite poisoning. Br Med J 1936; 1: 1300. 7. Standefer J, Jones J, Street E, Insera R. Death associated with nitrite ingestion: report of a case. J Forensic Sci 1979; 24: 768-771. 8. McQuiston T. Fatal poisoning by sodium nitrite. Lancet 1936; 2: 1153-1154. 9. Padberg L, Martin T. Three fatal cases of sodium nitrite poisoning. JAMA 1939; 113: 1733. 10. Manley C. A fatal case of sodium nitrite poisoning. Analyst 1945; 70: 50. 11. Barton G. A fatal case of sodium nitrite poisoning. Lancet 1954; 1: 190-191. 12. Blunt S. Rapid death of a child following sodium nitrite ingestion. Bull Int Asso For Tox 1973; 12(3): 15-17. 13. Hall AH, Kulig KW, Rumack BH. Drug- and chemical-induced methaemoglobinaemia: clinical features and management. Med Toxicol 1986; 1: 253-260.
Address for correspondence W J Gowans, 74 The Mount, Shrewsbury SY3 8PN.
College Publications
Il |EDUCATION FOR GENERAL PRACTICE iA Il*I_l The Future General Practitioner- Learning and Teaching M
.
A
A
A
A
Undergraduate Medical Education in General Practice
One of the RCGP's all-time best sellers. 'This stimulating and provocative book has been written by six outstanding general practitioners. It deserves to be read not only by teachers in general practice, but also by teachers in other fields of medicine' - British Medical Journal. £9.50 (£10.50 non-members)
(Occasional Paper 28) An AUTGP working group analyses the GMC recommendations on undergraduate medical education and the contribution which general £3.50 practice can make.
A System of Training for General Practice (Occasional Paper 4)
The Contribution of Academic General Practice to
Pereira Gray's 'best seller' describes the philosophy and aims of one department of general practice and outlines a practical method of £3.00 organizing training for gqeneral practice. Some Aims for Training for General Practice (Occasional Paper 6) Sets out the objectives for care agreed by the RCGP for trainees on the care of children, the elderly and the mentally ill. £2.75
Undergraduate Medical Education (Occasional Paper 42) The result of a questionnaire sent to all academic departments of general practice in the British Isles. Gives information on curricula, assessment
Fourth National Trainee Conference (Occasional Paper 18) This important survey of 1680 trainees describes how much teaching they £3.75 get, what they think of trainers and how to rate a trainer.
The Influence of Trainers on Trainees in General Practice (Occasional Paper 21) Reports a study in the north of England comparing two groups of trainees with the characteristics of their trainers. Useful for all involved in £3.25
training.
Priority Objectives for General Practice Vocational Training
(Occasional Paper
30)RaigSae
Sets out the Oxford region's priority objectives for training: primary care communication, organization, professional values and personal and professional growth.
£3.50
Course Organizers General Practce Practice (ccasonalPape (Occasional Paper 34) Cours OrgnizesiinnGeneal This report of a major national survey of course organizers provides the most comprehensive and up-to-date information available on the
£4.50 subject. Towards a Curriculum for General Practice Training (Occasional Paper 44) Examines several topical issues, including educational assessment, and
procedures, staff training and teaching methods.
£6.50
A What Sort of Doctor? (Report 23) Describes the most radical system so far published on the assessment of performance review by GPs in their own practices. £5.00
Practice Assessment and Quality of Care (Occasional Paper 39) An extensive review of the literature of assessment and quality in general
practice with special reference to practice visiting.
£5.00
erlPcte Practice in General for VoainlTann Vocational Training inG Rating Scales fo 1988 (Occasional Paper 40) A new set of 23 rating scales, with subscales, produced by the Department of General Practice at Manchester to enable trainers to monitor progress £5.00 of vocational trainees during their general practice year.
Practice Activity Analysis (Occasional Paper 41)
Describes the results of practice activity analysis undertaken by the RCGP Birmingham Research Unit over a number of years and discusses its role
as a practical approach to audit and assessment of quality.
£6.50
does not shirk from tackling some of the major problems about current £6.00 systems.
Section 63 Activities (Occasional Paper 11)
Education for Co-operation in Health and Social Work (Occasional Paper 14)
Tackles controversial topics, such as the effectiveness of activities provided under Section 63 and what the doctors responsible for them think.£3.75
Reports an interdisciplinary conference of social workers, nurses, health visitors and GPs: how they can co-operate and the difficulties
Continuing Education for General Practitioners (Occasional Paper 38) This investigation of the patterns of attendance at continuing education
involved.
meetings compares the characteristics of general practitioners who attend £5.00 regularly with those who attend occasionally or not at all.
£3.00
Working Together-Learning Together (Occasional Paper 33)
This reports the successes and failures of courses run over several years £3.00 to promote teamwork in general practice.
All the above can be obtained from the Sales Office, Royal College of General Practitioners, 14 Princes Gate, London SW7 1PU (Enquiries, Tel: 071-823 9698). Prices include postage. Payment should be made with order. Cheques should be made payable to RCGP Enterprises Ltd. Access and Visa welcome (Tel: 071-225 3048, 24 hours).
British Journal of General Practice, November 1990
471
Fatal methaemoglobinaemia in a dental nurse. A case of sodium nitrite poisoning W J GOWANS SUMMARY Methaemoglobinaemia may be caused by ingestion of a number of drugs, among them nitrites, some of which are remarkably toxic. This was tragically highlighted by the death of a 17 year old dental nurse after taking a single 1 g tablet of sodium nitrite. These tablets are widely used in the medical and dental profession to prevent rusting of instruments while immersed in disinfectant solutions. The toxicity of this chemical should be more widely recognized and its storage made correspondingly more secure. Methaemoglobinaemia should be considered as a diagnosis in any patient with significant central cyanosis in whom there is no obvious cardiorespiratory cause.
Case history M ISS H, a 17 year old dental nurse, was admitted to the casualty department at 18.30 hours after being found at home in an hysterical condition and bright blue. On admission she had central cyanosis, tachycardia and tachypnoea. Her chest was clear and she had a systolic blood pressure of 90 mmHg. No history was obtainable from her but her boyfriend reported that she had been fit and well earlier in the day and that he had not seen any evidence of drug ingestion at her house. Fifteen minutes after admission she vomited, aspirated and suffered a respiratory arrest. She was intubated and ventilated. Despite her cyanosis her arterial blood gases were normal. Apart from recent aspiration there was no other indication that her cyanosis was of cardiorespiratory origin. A venous blood sample was noted to be chocolate brown in colour. Methaemoglobinaemia was suspected and spectroscopy of a blood sample confirmed 'severe methaemoglobinaemia'. Forty five minutes after admission, methylene blue was administered intravenously (2 mg kg-' over 10 minutes). However, by 19.30 hours her blood pressure was unrecordable, a series of cardiac arrythmias ensued and, despite the insertion of a temporary pacing wire together with standard resuscitation measures, she failed to recover. She was certified dead at 20.30 hours, two hours after admission. Postmortem findings confirmed a normal cardiorespiratory system apart from evidence of minor aspiration into the upper lobe of the right lung. Biochemical analysis after death revealed that the level of methaemoglobinaemia was 35%, implying a much higher level on admission to hospital. The serum nitrite ion level was 13 mg 1-'. This level is consistent with death from nitrite poisoning following the ingestion of a single 1 g tablet of sodium nitrite.
Discussion The haemoglobin molecule is made up of four haem molecules each of which contains one iron atom in the Fe(II) state. Methaemoglobinaemia is caused by oxidation of one or more of the iron atoms to the Fe(III) state. Oxidation of a single haem changes the conformation of the haemoglobin molecule such W J Gowans, MRCP, MRCGP, medical registrar, Watford General Hospital. Submitted: 14 November 1989; accepted: 26 June 1990.
© British Journal qf General Practice, 1990, 40, 470-471.
470
that the oxygen affinity of the remaining three haem molecules is increased. The oxygen dissociation curve of methaemoglobin is shifted to the left compared with that for haemoglobin, resulting in impaired oxygen unloading to the tissues. The clinical effect of 30% methaemoglobinaemia is therefore much greater than an equivalent reduction in haemoglobin level. In more severe cases of acquired methaemoglobinaemia a haemolytic anaemia may ensue. A characteristic feature of methaemoglobinaemia is the chocolate brown appearance of whole blood which is said to be present at methaemoglobin concentrations as low as 15-20%. Acquired methaemoglobinaemia is caused by ingestion of or exposure to various oxidant drugs or chemicals. Chronic exposure to a low dose of oxidant may produce minimal methaemoglobinaemia and no symptoms whereas the acute ingestion of the same total dosage may be lethal. Treatment of chronic acquired methaemoglobinaemia involves withdrawal of the offending drug or chemical. If continued therapy is indicated then the dose of oxidant to which the patient is exposed should be reduced. Acute methaemoglobinaemia, if life threatening, should be treated with oxygen and intravenous methylene blue; both reduce levels of methaemoglobin. If there is intravascular haemolysis then plasmapheresis or exchange transfusion is indicated. The list of drugs which cause methaemoglobinaemia is long. It includes organic and inorganic nitrites, nitrates, local anaesthetics, dapsone, aniline dyes and sodium chlorate. Numerous cases of infant methaemoglobinaemia have resulted from consumption of rural well water high in nitrates which are converted into nitrites in the gut. Amyl or butyl nitrite is often abused as an inhalation intoxicant and to heighten orgasm and several cases of severe poisoning and deaths have been reported. 1-5 Serum nitrite levels in cases where death has followed accidental or intentional ingestion of sodium or potassium nitrite have varied from 0.5 to 340 mg 1-1.67 Serum nitrite levels vary widely between individuals who have ingested roughly equivalent doses of the same nitrite preparation. There are several reported cases of fatal sodium or potassium nitrite overdose in which the chemical has been identified in gastric contents but not in other body fluids or tissues.8-'2 The correlation between serum methaemoglobin concentrations and symptoms is more consistent. Cyanosis is detectable at serum methaemoglobin concentrations of 15%, 407o causes severe headache with weakness and ataxia while levels above 70% will cause severe cyanosis, tachycardia and dyspnoea with the risk of cardiovascular collapse and death.'3 Sodium nitrite tablets (1 g) are supplied as an adjunct to disinfectant fluids such as chlorhexidine. When dissolved in the fluid sodium nitrite acts as a strong oxidizing agent preventing rusting of the instruments being disinfected. The label on a sodium nitrite container indicates that the material is toxic by ingestion both in text and using the standard symbol of a skull and crossbones in black on an orange background. In the case just cited the dental nurse almost certainly obtained the tablet(s) from the practice in which she was employed. They were routinely left by the side of the disinfectant bath in which they were used. Furthermore, she probably took only one tablet; this being enough to produce a serum nitrite level that was lethal despite active treatment. The toxicity of sodium nitrite
British Journal of General Practice, November 1990
Case report
W J Gowans tablets is not widely known, despite their widespread use in the medical and dental professionis. If they are to be kept on surgery premises at all then secure storage must be guaranteed. This case serves to remind general practitioners to consider methaemoglobinaemia as a diagnosis in any patient with significant central cyanosis in whom there is no obvious cardiorespiratory cause.
References 1. Smith M, Stair T, Rolmick MA. Butyl nitrite and a suicide attempt. Ann Intern Med 1980; 92: 719. 2. Shesser R, Mitchell J, Edelstein S. Methaemoglobinaemia from isobutyl nitrite preparation. Ann Emerg Med 1981; 10: 262. 3. Home MK, Waterman MR, Simon LM, et al. Methaemoglobinaemia from sniffing butyl nitrite. Ann Intern Med 1979; 91: 417. 4. Shesser R, Dixon D, Allen Y, et al. Fatal methaemoglobinaemia from butyl nitrite ingestion. Ann Intern Med 1980; 92: 131. 5. Wason S, Detsky AS, Platt OS, Lovejoy FH. Isobutyl nitrite toxicity by ingestion. Ann Intern Med 1980; 92: 637.
6. Naidu S, Rao P. Case of nitrite poisoning. Br Med J 1936; 1: 1300. 7. Standefer J, Jones J, Street E, Insera R. Death associated with nitrite ingestion: report of a case. J Forensic Sci 1979; 24: 768-771. 8. McQuiston T. Fatal poisoning by sodium nitrite. Lancet 1936; 2: 1153-1154. 9. Padberg L, Martin T. Three fatal cases of sodium nitrite poisoning. JAMA 1939; 113: 1733. 10. Manley C. A fatal case of sodium nitrite poisoning. Analyst 1945; 70: 50. 11. Barton G. A fatal case of sodium nitrite poisoning. Lancet 1954; 1: 190-191. 12. Blunt S. Rapid death of a child following sodium nitrite ingestion. Bull Int Asso For Tox 1973; 12(3): 15-17. 13. Hall AH, Kulig KW, Rumack BH. Drug- and chemical-induced methaemoglobinaemia: clinical features and management. Med Toxicol 1986; 1: 253-260.
Address for correspondence W J Gowans, 74 The Mount, Shrewsbury SY3 8PN.
College Publications
Il |EDUCATION FOR GENERAL PRACTICE iA Il*I_l The Future General Practitioner- Learning and Teaching M
.
A
A
A
A
Undergraduate Medical Education in General Practice
One of the RCGP's all-time best sellers. 'This stimulating and provocative book has been written by six outstanding general practitioners. It deserves to be read not only by teachers in general practice, but also by teachers in other fields of medicine' - British Medical Journal. £9.50 (£10.50 non-members)
(Occasional Paper 28) An AUTGP working group analyses the GMC recommendations on undergraduate medical education and the contribution which general £3.50 practice can make.
A System of Training for General Practice (Occasional Paper 4)
The Contribution of Academic General Practice to
Pereira Gray's 'best seller' describes the philosophy and aims of one department of general practice and outlines a practical method of £3.00 organizing training for gqeneral practice. Some Aims for Training for General Practice (Occasional Paper 6) Sets out the objectives for care agreed by the RCGP for trainees on the care of children, the elderly and the mentally ill. £2.75
Undergraduate Medical Education (Occasional Paper 42) The result of a questionnaire sent to all academic departments of general practice in the British Isles. Gives information on curricula, assessment
Fourth National Trainee Conference (Occasional Paper 18) This important survey of 1680 trainees describes how much teaching they £3.75 get, what they think of trainers and how to rate a trainer.
The Influence of Trainers on Trainees in General Practice (Occasional Paper 21) Reports a study in the north of England comparing two groups of trainees with the characteristics of their trainers. Useful for all involved in £3.25
training.
Priority Objectives for General Practice Vocational Training
(Occasional Paper
30)RaigSae
Sets out the Oxford region's priority objectives for training: primary care communication, organization, professional values and personal and professional growth.
£3.50
Course Organizers General Practce Practice (ccasonalPape (Occasional Paper 34) Cours OrgnizesiinnGeneal This report of a major national survey of course organizers provides the most comprehensive and up-to-date information available on the
£4.50 subject. Towards a Curriculum for General Practice Training (Occasional Paper 44) Examines several topical issues, including educational assessment, and
procedures, staff training and teaching methods.
£6.50
A What Sort of Doctor? (Report 23) Describes the most radical system so far published on the assessment of performance review by GPs in their own practices. £5.00
Practice Assessment and Quality of Care (Occasional Paper 39) An extensive review of the literature of assessment and quality in general
practice with special reference to practice visiting.
£5.00
erlPcte Practice in General for VoainlTann Vocational Training inG Rating Scales fo 1988 (Occasional Paper 40) A new set of 23 rating scales, with subscales, produced by the Department of General Practice at Manchester to enable trainers to monitor progress £5.00 of vocational trainees during their general practice year.
Practice Activity Analysis (Occasional Paper 41)
Describes the results of practice activity analysis undertaken by the RCGP Birmingham Research Unit over a number of years and discusses its role
as a practical approach to audit and assessment of quality.
£6.50
does not shirk from tackling some of the major problems about current £6.00 systems.
Section 63 Activities (Occasional Paper 11)
Education for Co-operation in Health and Social Work (Occasional Paper 14)
Tackles controversial topics, such as the effectiveness of activities provided under Section 63 and what the doctors responsible for them think.£3.75
Reports an interdisciplinary conference of social workers, nurses, health visitors and GPs: how they can co-operate and the difficulties
Continuing Education for General Practitioners (Occasional Paper 38) This investigation of the patterns of attendance at continuing education
involved.
meetings compares the characteristics of general practitioners who attend £5.00 regularly with those who attend occasionally or not at all.
£3.00
Working Together-Learning Together (Occasional Paper 33)
This reports the successes and failures of courses run over several years £3.00 to promote teamwork in general practice.
All the above can be obtained from the Sales Office, Royal College of General Practitioners, 14 Princes Gate, London SW7 1PU (Enquiries, Tel: 071-823 9698). Prices include postage. Payment should be made with order. Cheques should be made payable to RCGP Enterprises Ltd. Access and Visa welcome (Tel: 071-225 3048, 24 hours).
British Journal of General Practice, November 1990
471
