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VENTRICULAR ARRHYTHMIAS DESPITE AN APPARENTLY CORRECTLY PLACED HICKMAN-BROVIAC CATHETER
924
Pathway of
urea
synthesis, showing
orotate as
an
overflow
metabolite of carbamoyl phosphate. CPS
=
carbamoyl phosphate synthetase; NAG N-acetylglutamate. =
We think that the predominant action of valproate in our studies indeed via inhibition of the synthesis of N-acetylglutamate, but that this affected ureagenesis by decreasing the synthesis of carbamoyl phosphate rather than by reducing the availability of aspartate for synthesis of argininosuccinate. If this is correct the hyperammonaemic action of valproate, and exogenous organic anion, would be strikingly similar to that occurring in genetic defects such as methylmalonic and propionic acidaemia, in which endogenous organic anions accumulate. This mechanism was proposed by Coulter and Allen in 1980.8
was
M. HJELM
Department of Clinical Biochemistry, Institute of Child Health, London WC1N 1EH
V. OBERHOLZER J. SEAKINS S. THOMAS
Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford OX1 9DU
showed that the tip of the catheter lay in the right atrium, this being confirmed by several subsequent X-rays over the next 8 days. She was hydrated and started on allopurinol 450 mg daily. 48 h later treatment was started with the MACHO regimen (cyclophosphamide, vincristine, ’Adriamycin’, high-dose methotrexate and intrathecal methotrexate, and cytarabine). Despite these precautions the tumour lysis syndrome ensued, the serum calcium falling to 0-9 mmol/1 (normal 2-2-2-8) and the serum magnesium to 0-33 mmol/1 (normal 0-76-1-03). Serum phosphate rose to 37 mmol/1 (normal 0-8-2-1), as did the potassium, to 62 mmolfl (normal 3-5-15). Her serum creatinine increased to 324 umol/1 (normal below 100). Although the calcium and potassium returned rapidly to normal with therapy, the magnesium was still much reduced on day 4 (0 43 mmol/1). 2 h after the administration of adriamycin on day 4 ventricular tachycardia developed. She was resuscitated with intravenous lignocaine, and the magnesium was fully corrected with intravenous supplements. A nucleotide scan revealed no decrease in cardiac function. However, over the next 4 days she continued to have prolonged runs of ventricular tachycardia despite a 2-4 mg/min lignocaine infusion. At this stage it was noted that arrhythmia occurred only when the patient was in a certain position, especially when she was leaning forward. Radiologically the catheter was unchanged in position, but despite this we felt that the catheter tip might be passing through the tricuspid valve and causing the ventricular arrhythmia. When the catheter was pulled back into the superior vena cava, the runs of tachycardia ceased. Ventricular arrhythmia is not an unexpected complication in a patient with multiple metabolic abnormalities and receiving cardiotoxic drugs. It is also a well recognised complication of Hickman-Broviac catheters when positioned inadvertently in the right ventricle. However, in this patient serial chest X-rays suggested that the catheter was always in the right atrium, and the cardiac function was normal. The possibility of a catheter passing intermittently through the tricuspid valve should therefore be remembered in such patients. Department of Haematology, Royal Liverpool Hospital, Liverpool L69 3BX
R. L. SPEARING
Alder Hey Children’s Hospital,
Liverpool
E.
J. MACKIE
Children’s Hospital, Birmingham
J. G. C. WRIGHT
MV, Hill RS, et al. Use of modified subcutaneous right atnal in leukaemic patients. Lancet 1980; i: 933-94. 2. Wade JC, Newman KA, et al. Two methods of improved venous access in acute leukemic patients. JAMA 1981; 246: 140-44. 3. Russell SJ, Giles FJ, Edwards D, et al. Perforation of superior vena cava by indwelling central venous catheters. Lancet 1987; i: 568-69. 1. Blacklock HA, Pillai
J. D. S. KAY
1. Hjelm M, Oberholzer V, Seakins J, Thomas S, Kay JDS. Valporate-induced inhibition of urea synthesis of hyperammonaemia in healthy subjects. Lancet 1986; ii: 859. 2. Warter JM, Brandt C, Marescaux C, et al. The renal origin of sodium valproateinduced hyperammonaemia in fasting humans. Neurology 1983; 33: 1136-40. 3. Warter JM, Marescaux C, Brandt C, et al. Sodium valproate associated with phenobarbital: effects on ammonia metabolism in humans. Epilepsia 1983; 24: 628-33. 4. Turnbull DM, Dick DJ, Wilson L, Sherratt HSA, Alberti KGMM. Valproate causes metabolic disturbance in normal man. J Neurol Neurosurg Psychiatry 1986; 49: 405-10. 5. Coude FX, Grimber G, Parvy P, Rabier D, Petit F. Inhibition of ureagenesis by valproate in rat hepatocytes. Biochem J 1983; 216: 233-36. 6. Bachmann C, Colombo JP. Diagnostic value of orotic add excretion in heritable disorders of the urea cycle and in hyperammonaemia due to organic acidurias. Eur J Pediatr 1980; 134: 109-13. 7. Sugimoto T, Matsumura T, Sakane Y. Hyperammonaemia and orotic add excretion following administration of valproate. Acta Paediatr Jpn 1982; 24: 336-38. 8. Coulter DL, Allen RJ. Secondary hyperammonaemia. A possible mechanism for valproate encephalopathy. Lancet 1980; i: 1310-11.
VENTRICULAR ARRHYTHMIAS DESPITE AN APPARENTLY CORRECTLY PLACED HICKMAN-BROVIAC CATHETER
SIR,-Indwelling right-atrial catheters (Hickman-Broviac) have greatly increased the ease with which drugs can be administered to patients with malignant disease. Complications reported include infection1, bleeding,2 pneumothorax, and thrombosis or perforation of the superior vena cava.3 A 12-year-old girl with stage til Burkitt’s lymphoma had a Hickman catheter inserted under general anaesthesia and an X-ray
venous access
SCIATIC-LIKE REFERRED PAIN AFTER RUBBERBAND HAEMORRHOIDAL LIGATION
SIR,-During April, 1985,
to
March, 1986, 196 patients had
rubberband ligations of haemorrhoids at our surgical outpatient clinic. Of these patients, 3 females and 1 male reported a sciatic-like pain on the same side in which the haemorrhoid was ligated, several hours after ligation. The pain was localised to the buttock, radiating to the back of the thigh, and was dull and constant in nature and not relieved by change in body position. Defaecation also did not alter the pain. The pain lasted up to one week after ligation. Neurological examination did not reveal signs of sciatic nerve root compression. The upper anal canal, like the rest of the gastrointestinal tract, is insensitive to painful stimuli such as cutting, crushing, or burning. This allows us to ligate internal haemorrhoids without anaesthesia.’ However, the gut is sensitive to distension or traction. Excessive tension or contraction and certain pathological conditions of smooth muscle can produce visceral pain.2 This pain may be truly visceral, related to the affected region, usually poorly localised, and described as dull or heavy. However, the pain may be referred to a skin region, the sensory nerve from which enters the same segment of the spinal cord as those which receive afferent fibres from the affected viscus.) In the pelvis the afferent sensory fibres run in the parasympathetic splanchnic nerves. These nerves innervate the pelvic viscera
Pathway of
urea
synthesis, showing
orotate as
an
overflow
metabolite of carbamoyl phosphate. CPS
=
carbamoyl phosphate synthetase; NAG N-acetylglutamate. =
We think that the predominant action of valproate in our studies indeed via inhibition of the synthesis of N-acetylglutamate, but that this affected ureagenesis by decreasing the synthesis of carbamoyl phosphate rather than by reducing the availability of aspartate for synthesis of argininosuccinate. If this is correct the hyperammonaemic action of valproate, and exogenous organic anion, would be strikingly similar to that occurring in genetic defects such as methylmalonic and propionic acidaemia, in which endogenous organic anions accumulate. This mechanism was proposed by Coulter and Allen in 1980.8
was
M. HJELM
Department of Clinical Biochemistry, Institute of Child Health, London WC1N 1EH
V. OBERHOLZER J. SEAKINS S. THOMAS
Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford OX1 9DU
showed that the tip of the catheter lay in the right atrium, this being confirmed by several subsequent X-rays over the next 8 days. She was hydrated and started on allopurinol 450 mg daily. 48 h later treatment was started with the MACHO regimen (cyclophosphamide, vincristine, ’Adriamycin’, high-dose methotrexate and intrathecal methotrexate, and cytarabine). Despite these precautions the tumour lysis syndrome ensued, the serum calcium falling to 0-9 mmol/1 (normal 2-2-2-8) and the serum magnesium to 0-33 mmol/1 (normal 0-76-1-03). Serum phosphate rose to 37 mmol/1 (normal 0-8-2-1), as did the potassium, to 62 mmolfl (normal 3-5-15). Her serum creatinine increased to 324 umol/1 (normal below 100). Although the calcium and potassium returned rapidly to normal with therapy, the magnesium was still much reduced on day 4 (0 43 mmol/1). 2 h after the administration of adriamycin on day 4 ventricular tachycardia developed. She was resuscitated with intravenous lignocaine, and the magnesium was fully corrected with intravenous supplements. A nucleotide scan revealed no decrease in cardiac function. However, over the next 4 days she continued to have prolonged runs of ventricular tachycardia despite a 2-4 mg/min lignocaine infusion. At this stage it was noted that arrhythmia occurred only when the patient was in a certain position, especially when she was leaning forward. Radiologically the catheter was unchanged in position, but despite this we felt that the catheter tip might be passing through the tricuspid valve and causing the ventricular arrhythmia. When the catheter was pulled back into the superior vena cava, the runs of tachycardia ceased. Ventricular arrhythmia is not an unexpected complication in a patient with multiple metabolic abnormalities and receiving cardiotoxic drugs. It is also a well recognised complication of Hickman-Broviac catheters when positioned inadvertently in the right ventricle. However, in this patient serial chest X-rays suggested that the catheter was always in the right atrium, and the cardiac function was normal. The possibility of a catheter passing intermittently through the tricuspid valve should therefore be remembered in such patients. Department of Haematology, Royal Liverpool Hospital, Liverpool L69 3BX
R. L. SPEARING
Alder Hey Children’s Hospital,
Liverpool
E.
J. MACKIE
Children’s Hospital, Birmingham
J. G. C. WRIGHT
MV, Hill RS, et al. Use of modified subcutaneous right atnal in leukaemic patients. Lancet 1980; i: 933-94. 2. Wade JC, Newman KA, et al. Two methods of improved venous access in acute leukemic patients. JAMA 1981; 246: 140-44. 3. Russell SJ, Giles FJ, Edwards D, et al. Perforation of superior vena cava by indwelling central venous catheters. Lancet 1987; i: 568-69. 1. Blacklock HA, Pillai
J. D. S. KAY
1. Hjelm M, Oberholzer V, Seakins J, Thomas S, Kay JDS. Valporate-induced inhibition of urea synthesis of hyperammonaemia in healthy subjects. Lancet 1986; ii: 859. 2. Warter JM, Brandt C, Marescaux C, et al. The renal origin of sodium valproateinduced hyperammonaemia in fasting humans. Neurology 1983; 33: 1136-40. 3. Warter JM, Marescaux C, Brandt C, et al. Sodium valproate associated with phenobarbital: effects on ammonia metabolism in humans. Epilepsia 1983; 24: 628-33. 4. Turnbull DM, Dick DJ, Wilson L, Sherratt HSA, Alberti KGMM. Valproate causes metabolic disturbance in normal man. J Neurol Neurosurg Psychiatry 1986; 49: 405-10. 5. Coude FX, Grimber G, Parvy P, Rabier D, Petit F. Inhibition of ureagenesis by valproate in rat hepatocytes. Biochem J 1983; 216: 233-36. 6. Bachmann C, Colombo JP. Diagnostic value of orotic add excretion in heritable disorders of the urea cycle and in hyperammonaemia due to organic acidurias. Eur J Pediatr 1980; 134: 109-13. 7. Sugimoto T, Matsumura T, Sakane Y. Hyperammonaemia and orotic add excretion following administration of valproate. Acta Paediatr Jpn 1982; 24: 336-38. 8. Coulter DL, Allen RJ. Secondary hyperammonaemia. A possible mechanism for valproate encephalopathy. Lancet 1980; i: 1310-11.
VENTRICULAR ARRHYTHMIAS DESPITE AN APPARENTLY CORRECTLY PLACED HICKMAN-BROVIAC CATHETER
SIR,-Indwelling right-atrial catheters (Hickman-Broviac) have greatly increased the ease with which drugs can be administered to patients with malignant disease. Complications reported include infection1, bleeding,2 pneumothorax, and thrombosis or perforation of the superior vena cava.3 A 12-year-old girl with stage til Burkitt’s lymphoma had a Hickman catheter inserted under general anaesthesia and an X-ray
venous access
SCIATIC-LIKE REFERRED PAIN AFTER RUBBERBAND HAEMORRHOIDAL LIGATION
SIR,-During April, 1985,
to
March, 1986, 196 patients had
rubberband ligations of haemorrhoids at our surgical outpatient clinic. Of these patients, 3 females and 1 male reported a sciatic-like pain on the same side in which the haemorrhoid was ligated, several hours after ligation. The pain was localised to the buttock, radiating to the back of the thigh, and was dull and constant in nature and not relieved by change in body position. Defaecation also did not alter the pain. The pain lasted up to one week after ligation. Neurological examination did not reveal signs of sciatic nerve root compression. The upper anal canal, like the rest of the gastrointestinal tract, is insensitive to painful stimuli such as cutting, crushing, or burning. This allows us to ligate internal haemorrhoids without anaesthesia.’ However, the gut is sensitive to distension or traction. Excessive tension or contraction and certain pathological conditions of smooth muscle can produce visceral pain.2 This pain may be truly visceral, related to the affected region, usually poorly localised, and described as dull or heavy. However, the pain may be referred to a skin region, the sensory nerve from which enters the same segment of the spinal cord as those which receive afferent fibres from the affected viscus.) In the pelvis the afferent sensory fibres run in the parasympathetic splanchnic nerves. These nerves innervate the pelvic viscera