Toxicity after intermittent inhalation of nitrous oxide for analgesia
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《英国医生杂志》
1 Wrexham Maelor Hospital, Wrexham LL13 7TD
Correspondence to: M Doran mark.doran@thewaltoncentre.nhs.uk
Introduction
A 21 year old man presented with a short history of being unable to stand. He had had a series of serious operations for the treatment for inflammatory bowel disease over a four year period—colectomy, ileostomy, and laparotomy with the formation of an ileoanal pouch. He developed pelvic sepsis requiring the laying open of an extensive perineal abscess.
The provision of postoperative analgesia for a perineal abscess proved difficult, during daily changes of packs to the cavity. Doctors gave paracetamol, diclofenac, regular oral slow release opioids, morphine tablets, and a 50:50 mixture of nitrous oxide and oxygen for managing the incident pain while changing dressings.
The hospital gave the man a 300 litre cylinder of the mixture as a short term arrangement over the Christmas period to provide analgesia for dressing changes. The man was to be readmitted after two weeks for review. When he was not readmitted as planned, his family arranged for replacement with larger cylinders. The hospital issued increasing amounts during four months, resulting in the weekly consumption of 1280 litres of nitrous oxide mixture. The district nurses contacted the hospital's pain team to express concern about the amount of mixture that the patient was using.
The man had had progressive severe difficulty in walking for six weeks, so his general practitioner referred him to a neurologist with no reference to the use of nitrous oxide. The neurologist diagnosed him as having a spinal cord disorder and admitted him to hospital for more detailed investigation.
On admission, the patient weighed 60 kg; he had a drain in the rectal pouch and reported severe pain in his perineum. He was unable to hold a cup or put on his glasses owing to severe lack of coordination and was unable to stand independently owing to severe ataxia.
The patient reported that his only drugs at that time were the standard analgesics, vitamin and mineral supplements, iron sulphate, citalopram, zinc, and paracetamol. Neurological examination showed severe pseudo-athetosis of the fingers and arms, and motor examination of his arms and legs, brisk reflexes and bilateral flexor plantar responses was normal. Sensory examination found severe loss of joint position sense in the hands and feet and loss of vibration sense in all four limbs with no spinothalamic sensory loss or trunkal sensory level.
He was diagnosed as having a dorsal column spinal syndrome (probably subacute combined degeneration), and doctors gave 1000 μg hydroxocobalamine (vitamin B-12) after taking blood for vitamin B-12 and other haematological and biochemical estimations.
Concentration of vitamin B-12 was slightly below the normal range (269 ng/l; normal > 300 ng/l). Serum and red cell folate were normal. The patient denied having taken folate or vitamin B-12 antagonists.
A long lesion of the dorsal column, typical of subacute combined degeneration, was evident in a magnetic resonance imaging scan of the cervical spinal cord (figure).
Magnetic resonance image showing dorsal column lesion (arrow) of the spinal cord
Transverse myelitis was a possible differential radiological diagnosis in view of the normal vitamin B-12 concentration. Viral and atypical bacterial organism serological tests were negative. Because of pelvic sepsis and the man's evident rapid improvement, a lumbar puncture was not done.
After his discharge the neurological team learnt that the man had been taking nitrous oxide, explaining the paradoxical clinical picture of subacute combined degeneration with normal vitamin B-12 and folate concentrations. Appropriate aftercare was arranged with further injections of vitamin B-12 and to provide psychological support to manage his evident addiction.
On follow up at three months the man had no gait ataxia and normal hand function and was independent in all activities of daily living. The case illustrates the need to be aware of adverse effects of all drugs—even those considered to be among the safest.
Discussion
Filippo TS, Holder WD. Neurologic degeneration associated with nitrous oxide anaesthesia in patients with vitamin B12 deficiency. Arch Surg 1993;128: 1391-5.
Schilling RF. Is nitrous oxide a dangerous anaesthetic for vitamin B12 deficient subjects? JAMA 1986;255: 1605-6.
Small DH, Carnegie PR, Anderson R McD. Inhibition of protein methylation in myelin mimics lesions due to vitamin B12 deficiency. Proc Aust Biochem Soc 1980;13: 113.
Ilniczky S, Jelencsik I, Kenez J, Szirmai I. MR findings in subacute combined degeneration of the spinal cord caused by nitrous oxide anaesthesia—two cases. Eur J Neurol 2002;9: 101-4.
Iwata K, O'Keefe GB, Karanas A. Neurologic problems associated with nitrous oxide abuse in a non-healthcare worker. Am J Med Sci 2001;322: 173-4.
Louis-Ferdinand RT. Myelotoxic, neurotoxic and reproductive adverse effects of nitrous oxide. Adverse Drug React Toxicol Rev 1994;13: 193-206.
Koblin DD, Everman BW. Vitamin B12 and folate status in rats after chronic administration of ethanol and acute exposure to nitrous oxide. Alcohol Clin Exp Res 1991;15: 543-8.
Abdul-Kareen HS, Sharma RP, Drown DB. Effects of repeated intermittent exposures to nitrous oxide on central neurotransmitters and hepatic methionine synthetase activity in CD-1 mice. Toxicol Ind Health 1991;7: 97-108.(Mark Doran, consultant ne)
Correspondence to: M Doran mark.doran@thewaltoncentre.nhs.uk
Introduction
A 21 year old man presented with a short history of being unable to stand. He had had a series of serious operations for the treatment for inflammatory bowel disease over a four year period—colectomy, ileostomy, and laparotomy with the formation of an ileoanal pouch. He developed pelvic sepsis requiring the laying open of an extensive perineal abscess.
The provision of postoperative analgesia for a perineal abscess proved difficult, during daily changes of packs to the cavity. Doctors gave paracetamol, diclofenac, regular oral slow release opioids, morphine tablets, and a 50:50 mixture of nitrous oxide and oxygen for managing the incident pain while changing dressings.
The hospital gave the man a 300 litre cylinder of the mixture as a short term arrangement over the Christmas period to provide analgesia for dressing changes. The man was to be readmitted after two weeks for review. When he was not readmitted as planned, his family arranged for replacement with larger cylinders. The hospital issued increasing amounts during four months, resulting in the weekly consumption of 1280 litres of nitrous oxide mixture. The district nurses contacted the hospital's pain team to express concern about the amount of mixture that the patient was using.
The man had had progressive severe difficulty in walking for six weeks, so his general practitioner referred him to a neurologist with no reference to the use of nitrous oxide. The neurologist diagnosed him as having a spinal cord disorder and admitted him to hospital for more detailed investigation.
On admission, the patient weighed 60 kg; he had a drain in the rectal pouch and reported severe pain in his perineum. He was unable to hold a cup or put on his glasses owing to severe lack of coordination and was unable to stand independently owing to severe ataxia.
The patient reported that his only drugs at that time were the standard analgesics, vitamin and mineral supplements, iron sulphate, citalopram, zinc, and paracetamol. Neurological examination showed severe pseudo-athetosis of the fingers and arms, and motor examination of his arms and legs, brisk reflexes and bilateral flexor plantar responses was normal. Sensory examination found severe loss of joint position sense in the hands and feet and loss of vibration sense in all four limbs with no spinothalamic sensory loss or trunkal sensory level.
He was diagnosed as having a dorsal column spinal syndrome (probably subacute combined degeneration), and doctors gave 1000 μg hydroxocobalamine (vitamin B-12) after taking blood for vitamin B-12 and other haematological and biochemical estimations.
Concentration of vitamin B-12 was slightly below the normal range (269 ng/l; normal > 300 ng/l). Serum and red cell folate were normal. The patient denied having taken folate or vitamin B-12 antagonists.
A long lesion of the dorsal column, typical of subacute combined degeneration, was evident in a magnetic resonance imaging scan of the cervical spinal cord (figure).
Magnetic resonance image showing dorsal column lesion (arrow) of the spinal cord
Transverse myelitis was a possible differential radiological diagnosis in view of the normal vitamin B-12 concentration. Viral and atypical bacterial organism serological tests were negative. Because of pelvic sepsis and the man's evident rapid improvement, a lumbar puncture was not done.
After his discharge the neurological team learnt that the man had been taking nitrous oxide, explaining the paradoxical clinical picture of subacute combined degeneration with normal vitamin B-12 and folate concentrations. Appropriate aftercare was arranged with further injections of vitamin B-12 and to provide psychological support to manage his evident addiction.
On follow up at three months the man had no gait ataxia and normal hand function and was independent in all activities of daily living. The case illustrates the need to be aware of adverse effects of all drugs—even those considered to be among the safest.
Discussion
Filippo TS, Holder WD. Neurologic degeneration associated with nitrous oxide anaesthesia in patients with vitamin B12 deficiency. Arch Surg 1993;128: 1391-5.
Schilling RF. Is nitrous oxide a dangerous anaesthetic for vitamin B12 deficient subjects? JAMA 1986;255: 1605-6.
Small DH, Carnegie PR, Anderson R McD. Inhibition of protein methylation in myelin mimics lesions due to vitamin B12 deficiency. Proc Aust Biochem Soc 1980;13: 113.
Ilniczky S, Jelencsik I, Kenez J, Szirmai I. MR findings in subacute combined degeneration of the spinal cord caused by nitrous oxide anaesthesia—two cases. Eur J Neurol 2002;9: 101-4.
Iwata K, O'Keefe GB, Karanas A. Neurologic problems associated with nitrous oxide abuse in a non-healthcare worker. Am J Med Sci 2001;322: 173-4.
Louis-Ferdinand RT. Myelotoxic, neurotoxic and reproductive adverse effects of nitrous oxide. Adverse Drug React Toxicol Rev 1994;13: 193-206.
Koblin DD, Everman BW. Vitamin B12 and folate status in rats after chronic administration of ethanol and acute exposure to nitrous oxide. Alcohol Clin Exp Res 1991;15: 543-8.
Abdul-Kareen HS, Sharma RP, Drown DB. Effects of repeated intermittent exposures to nitrous oxide on central neurotransmitters and hepatic methionine synthetase activity in CD-1 mice. Toxicol Ind Health 1991;7: 97-108.(Mark Doran, consultant ne)