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METHAEMOGLOBINAEMIA FOLLOWING THE USE OF PRILOCAINE (“CITANEST”)
Brit. J. Anaesth. (1964), 36, 737
METHAEMOGLOBINAEMIA FOLLOWING THE USE OF PRILOCAINE ("OTANEST") A Preliminary Report BY
SUMMARY
A series of eighty-one consecutive cases is reported in which continuous lumbar epidural block was performed on women in labour, prilocaine (Citanest) being the agent used. Nine cases showed cyanosis, and in seven of these spectroscopic examination of the blood showed methaemoglobinaemia. The relationship of prilocaine to aniline derivatives, known to cause methaemoglobinaemia, is mentioned. In recognition of the dangers of general anaesthesia in the labour ward, the use of pudendal and lumbar and sacral epidural blocks has been steadily increasing in this hospital for operative deliveries. Continuous lumbar and sacral epidural blocks have been found valuable also as a method of pain relief and in certain cases of inco-ordinate uterine action. Until the latter half of 1963, lignocaine was the agent used for this purpose, but following representation by the manufacturers that prilocaine (Citanest) was safer, a change was made to this drug in August of that year. Since this time several of these blocks have been followed by cyanosis unrelieved by oxygen, and laboratory examination of the blood has revealed the presence of methaemoglobin in a proportion of these cases. CASE 1.
Details of continuous sacral epidural analgesia. September 3, 10.45 p.m., 28 ml of 1 per cent prilocaine given via continuous epidural catheter. Further doses were given as follows: September 4, 5.30 a.m., 26 ml; 7.45 a.m., 26 ml; 9.45 ajn., 26 ml; 12 noon 26 ml; 1.30 p.m., 20 ml; 2.55 p.m., 26 ml. At 5.15 p.m. on September 4 the patient became very cyanosed, with both skin and mucous membranes dark blue in colour. Oxygen, administered at first by means of a nasal catheter and then with a bag and facepiece, effected no improvement. At 8.30 p.m., after a 24-hour labour, forceps delivery was carried out under general anaesthesia, resulting in a living female infant A specimen of blood taken at 9 p.m. showed no methaemoglobin on spectroscopic examination. The patient remained cyanosed for several hours, but her colour appeared normal by next morning. The total dose of 1 per cent prilocaine used in this case was 1520 mg. CASE 2.
A primigravida, aged 29, attended the antenatal clinic regularly from the 16th week. She was admitted to hospital three times during pregnancy for treatment of mild pre-eclamptic toxaemia. Labour began on Novemmer 18, 1963, and was prolonged, lasting 41 hours, Because of inco-ordinate uterine action, an oxytocin drip and a continuous lumbar epidural block were used in an effort to shorten labour.
A primigravida, aged 23, attended the antenatal clinic from 18 weeks gestation. There were no complications during pregnancy. She was admitted at term on September 3, 1963, with a history of painless blood loss. Details of continuous lumbar epidural analgesia. There were no contractions, the membranes were intact November 19, 10 a.m., 20 ml of 1 per cent prilocaine and the head was not engaged. An examination under given via lumbar epidural catheter. 1 p.m., additional 20 general anaesthesia was carried out but no placenta ml given; 5.20 p.m. additional 20 ml given for manual praevia was detected and the forewaters were ruptured, rotation and extraction with Kielland's forceps. clear liquor being obtained. Four hours later uterine In this case cyanosis appeared at 2.30 p.m. on contractions had not commenced and an oxytocin drip November 19 after the second injection of prilocaine, was started. After a further 4 hours the cervix was 2.5 i.e. after a total dose of 400 mg of the drug. Blood cm dilated and the vertex was at the level of the ischial was taken for spectroscopic examination at 4.20 p.m. spines. A continuous sacral epidural block was com- on the same day and methaemoglobin was found to be menced as the patient had become distressed by pain. present. 737
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on July 30, 2015
D. J. DALY, J. DAVENPORT AND M. C. NEWLAND
Department of Anaesthesia, The Queen Victoria Maternity Hospital, Adelaide, South Australia
738 CASE 3.
A primigravida, aged 18, attended the antenatal clinic regularly from the 20th week, her antenatal progress being uncomplicated. Labour commenced spontaneously at term on May 1, 1964, and lasted 30 hours. A continuous lumbar epidural block was used, the indication being inco-ordinate uterine action.
CASE 4.
A primigravida, aged 24. Her antenatal period was complicated by moderate pre-eclamptic toxaemia and hydramnios. Following two unsuccessful medical inductions with oxytocin drips the membranes were ruptured on May 20, 1964, and another oxytocin drip was started. Because of prolonged incoordinate labour and maternal distress a lumbar epidural block was commenced in the first stage.
The total dose of prilocaine was 790 mg. The patient became cyanosed after the last injection of prilocaine, remaining so for about 12 hours, and showing no improvement with the administration of oxygen. Spectroscopic examination of the mother's blood taken 1 hour after the onset of cyanosis showed the presence of methaemoglobin. CASE 6.
A primigravida, aged 26. This patient had an uncomplicated pregnancy. She was admitted on July 11, 1964, having had a slight show; membranes were intact and regular contractions were present. Progress was slow during the first stage because of inco-ordinate uterine action, and at 11.30 a.m. on July 13 a continuous lumbar epidural was begun. Details of continuous lumbar epidural analgesia. July 13, 11.30 a.m., 15 ml of 1 per cent prilocaine. Further doses were given on the same day as follows: 12.50 p.m., 15 ml; 4 p.m., 15 ml; 4.20 pjn. 5 ml; 5.25 p.m., 20 ml; 6.30 p.m. 20 ml. The total dose of prilocaine was 900 mg. At 7 p.m. cyanosis was first noticed. Two hours later she was given 10 ml of 1 per cent methylene blue intravenously over 5 minutes. Within half an hour the cyanosis had improved and a Caesarean section was commenced. The mother's blood remained dark throughout the operation but the baby cried soon after birth and showed no obvious cyanosis. A specimen of maternal blood, taken immediately before the administration of methylene blue, showed methaemoglobin on spectroscopic examination. CASE 7.
Details of continuous lumbar epidural analgesia. May 21, 12.40 a.m., 10 ml of 1 per cent prilocaine. Further doses were given as follows on the same day: 2 a.m., 10 ml; 3.30 a.m., 10 ml; 4.30 a.m., 20 ml; 6 a.m., 10 ml; 7 a.m., 10 ml; 8 a.m., 20 ml. At 9.30 a.m. a living male infant was delivered instrumentally. The total dose of 1 per cent prilocaine was 900 mg. At approximately 9.30 a.m. the patient appeared cyanosed. The cyanosis did not respond to oxygen and persisted for approximately 8 hours. A specimen of the mother's blood was taken 1 hour after the onset of cyanosis and found to be negative for methaemoglobin. CASE 5.
This patient, aged 27, had had a Caesarean section two years previously after a labour lasting three days. Her antenatal progress was uncomplicated, and the membranes were artificially ruptured at term on June 7, 1964. Labour commenced 7 hours later. The patient became extremely apprehensive and, in order to relieve pain, a continuous lumbar epidural block was started. Details of continuous lumbar epidural analgesia. June 7, 5.45 p.m., 10 ml of 1 per cent prilocaine. Further doses were given as follows on the same day: 6.45 p.m. 10 ml; 7.30 p.m. 10 ml; 8.15 p.m. 12 ml; 9.50 p.m. 20 ml; 10.50 p.m. 12 ml. Delivered with vacuum extractor of living female infant After delivery a further 5 ml of 1 per cent prilocaine were infiltrated into the perineum for repair of the episiotomy.
A primigravida, aged 20, had a pregnancy complicated by hydramnios and mild pre-eclamptic toxaemia. She was admitted on July 17, 1964, with a history of contractions at 5-minute intervals for 3 hours. There was no show and membranes were intact At 12.15 p.m. on July 18, because of slow progress in the first stage, a continuous lumbar epidural was begun. Details of continuous lumbar epidural analgesia. July 18. 12.15 p.m., 15 ml of 1 per cent prilocaine. Subsequent doses were given as follows: 1.45 pjn., 15 ml; 4.05 p.m., 15 ml; 7.45 p.m., 15 ml; July 19, 1 a.m., 10 ml; 2 a.m. 15 ml. The total dose of prilocaine was 850 mg. At 2 a.m. on July 19 the patient became cyanosed and was given 100 mg of vitamin C intramuscularly. This dose was repeated at 7 a.m. At 11 sum. on the same day the patient had a forceps delivery under general anaesthesia, the baby being resuscitated with some difficulty. The cyanosis persisted for a further hour after delivery. Blood was taken for methaemoglobin estimation at the time cyanosis was first apparent and was positive spectroscopicalry for methaemoglobin. DISCUSSION
Methaemoglobinaemia is a condition in which cyanosis occurs in the absence of cardiac or respiratory disease, due to the presence of excessive amounts of methaemoglobin in the blood. The majority of cases are due to exposure to nitxo or
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on July 30, 2015
Details of continuous lumbar epidural analgesia. May 1, 3.30 p.m., 10 ml of 1 per cent prilocaine given via lumbar epidural catheter. Further quantities of the same solution were given as follows: 5.45 pjn., 10 ml, 6.45 p.m,. 10 ml; 8.15 p.m., 10 ml; 9.45 p.m., 10 ml; 10.15 p.m., 10 ml; 11.15 p.m., 10 ml; May 2, 12.15 a.m., 10 ml; 2.35 a.m., 10 ml; 4.45 a.m., 10 ml; 6 ajn., 10 ml; 8.30 a.m., 10 ml. Forceps rotation and extraction were performed at full dilatation, resulting in delivery of a living female infant Cyanosis of the lips and fingers was noticed at 11.15 pjn. on May 1 after the sixth dose of prilocaine, Le. after a total dose of 500 mg. Blood taken soon after this revealed methaemoglobin on spectroscopic examination. The cyanosis persisted for some 12 hours.
BRITISH JOURNAL OF ANAESTHESIA
METHAEMOGLOBINAEMIA FOLLOWING THE USE OF PRILOCAINE
,CH2CH3
NH-CO-CH 2 -M \
CH 2 CH 3
Lignocaine
ADDENDUM
Since the compilation of this report, two further cases of confirmed methaemoglobinaemia have occurred following the use of 1 per cent prilocaine for epidural analgesia. This brings the number of cases showing cyanosis to nine out of a total of eighty-two cases who received 1 per cent prilocaine for this purpose. Previously, while using 1 per cent lignocaine, no cases of cyanosis were recognized out of a total of 360 blocks of this type. ACKNOWLEDGMENTS
Thanks are due to the Medical Superintendent of the Queen Victoria Maternity Hospital, Dr. L K. Furler, for much helpful advice and for permission to publish this report Also to Dr. R. N. Ibbotson of the Institute of Medical and Veterinary Science, Adelaide, for his help in the laboratory aspects of the investigation.
CH 3 REFERENCE
U
\
NH- CO-CH - NH-CH 2 CH 2 CH 3 CH3
Goodman, L. S., and Gilman, A. (1955). The Pharmacological Basis of Therapeutics, 2nd ed, p. 314. New York: Macmillan.
Prilocaine Fra. 1 Structural formulae of lignocaine and prilocaine.
The laboratory examination of the blood in these cases was done by means of a Hartridge reversion spectroscope. Though methaemoglobin was detected by this means in the blood of only five out of the seven cases showing cyanosis, it seems possible that it was the cause of the cyanosis in the remaining two cases. If this is so, the discrepancy may be due to lack of sensitivity in the spectroscopic examination, or perhaps to reduction of a significant amount of methaemoglobin between the time of taking the specimen of blood and of examining it in the laboratory. This preliminary report is submitted to bring to notice the possibility of methaemoglobinaemia following the use of prilocaine, a search of the literature having failed to reveal any reference to this matter. Further work is proceeding in this hospital with a view to clarifying the problem.
METHEMOGLOBINEMIB APRES USAGE DE PRILOCAINE (CrTANEST) SOMMAFRE
Une sdrie de quatre-vingt-et-un cas consecutifs ou un blocage Epidural lombaire continue a 6t6 realise1 chez des femmes en travail, est analyses. L'anesthesique utilise1 6tait la prilocaine (Citanest). Neuf cas presentaient une cyanose et dans sept de ces cas l'examen spectroscopique du sang montrait une me'the'moglobin^mie. Les rapports de la prilocaine avec certains derives de l'aniline connus pour provoquer de la me'the'moglobine'mie, sont discute's.
METHAMOGLOBINAMIE NACH ANWENDUNG VON PRILOCAINE (CITANEST) ZUSAMMENFASSUNO
Es wird Uber eine Serie von einundachtzig kreiflenden Frauen. bei denen eine kontinuierliche PeriduralanSsthesie im Lumbarbereich unter Verwendung von Prilocaine (Citanest) vorgenommen wurde. berichtet Bei neun Fallen wurde Zyanose beobachtet, bei sieben von diesen Fallen wurde bei der spektroskopischen Untersuchung des Blutes Methamoglobinamie festgestellt Die Verwandtschaft zwischen Prilocaine und den Anilinderivaten, von denen bekannt ist, dafi sie Methamoglobinamie verursachen, wird erwahnt.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on July 30, 2015
amino derivatives which are used extensively in industry for various purposes, e.g. in the synthesis of aniline dyes. The aniline derivatives acetanilide and acetophenetidin (phenacetin) are frequently incriminated (Goodman and Gilman, 1955). Lignocaine and prilocaine are related compounds (fig. 1), lignocaine being diethylamino -2, 6-dimethyl acetanilide, and prilocaine being a-n-propylamino 2-methyl-propionanilide.
739
METHAEMOGLOBINAEMIA FOLLOWING THE USE OF PRILOCAINE ("OTANEST") A Preliminary Report BY
SUMMARY
A series of eighty-one consecutive cases is reported in which continuous lumbar epidural block was performed on women in labour, prilocaine (Citanest) being the agent used. Nine cases showed cyanosis, and in seven of these spectroscopic examination of the blood showed methaemoglobinaemia. The relationship of prilocaine to aniline derivatives, known to cause methaemoglobinaemia, is mentioned. In recognition of the dangers of general anaesthesia in the labour ward, the use of pudendal and lumbar and sacral epidural blocks has been steadily increasing in this hospital for operative deliveries. Continuous lumbar and sacral epidural blocks have been found valuable also as a method of pain relief and in certain cases of inco-ordinate uterine action. Until the latter half of 1963, lignocaine was the agent used for this purpose, but following representation by the manufacturers that prilocaine (Citanest) was safer, a change was made to this drug in August of that year. Since this time several of these blocks have been followed by cyanosis unrelieved by oxygen, and laboratory examination of the blood has revealed the presence of methaemoglobin in a proportion of these cases. CASE 1.
Details of continuous sacral epidural analgesia. September 3, 10.45 p.m., 28 ml of 1 per cent prilocaine given via continuous epidural catheter. Further doses were given as follows: September 4, 5.30 a.m., 26 ml; 7.45 a.m., 26 ml; 9.45 ajn., 26 ml; 12 noon 26 ml; 1.30 p.m., 20 ml; 2.55 p.m., 26 ml. At 5.15 p.m. on September 4 the patient became very cyanosed, with both skin and mucous membranes dark blue in colour. Oxygen, administered at first by means of a nasal catheter and then with a bag and facepiece, effected no improvement. At 8.30 p.m., after a 24-hour labour, forceps delivery was carried out under general anaesthesia, resulting in a living female infant A specimen of blood taken at 9 p.m. showed no methaemoglobin on spectroscopic examination. The patient remained cyanosed for several hours, but her colour appeared normal by next morning. The total dose of 1 per cent prilocaine used in this case was 1520 mg. CASE 2.
A primigravida, aged 29, attended the antenatal clinic regularly from the 16th week. She was admitted to hospital three times during pregnancy for treatment of mild pre-eclamptic toxaemia. Labour began on Novemmer 18, 1963, and was prolonged, lasting 41 hours, Because of inco-ordinate uterine action, an oxytocin drip and a continuous lumbar epidural block were used in an effort to shorten labour.
A primigravida, aged 23, attended the antenatal clinic from 18 weeks gestation. There were no complications during pregnancy. She was admitted at term on September 3, 1963, with a history of painless blood loss. Details of continuous lumbar epidural analgesia. There were no contractions, the membranes were intact November 19, 10 a.m., 20 ml of 1 per cent prilocaine and the head was not engaged. An examination under given via lumbar epidural catheter. 1 p.m., additional 20 general anaesthesia was carried out but no placenta ml given; 5.20 p.m. additional 20 ml given for manual praevia was detected and the forewaters were ruptured, rotation and extraction with Kielland's forceps. clear liquor being obtained. Four hours later uterine In this case cyanosis appeared at 2.30 p.m. on contractions had not commenced and an oxytocin drip November 19 after the second injection of prilocaine, was started. After a further 4 hours the cervix was 2.5 i.e. after a total dose of 400 mg of the drug. Blood cm dilated and the vertex was at the level of the ischial was taken for spectroscopic examination at 4.20 p.m. spines. A continuous sacral epidural block was com- on the same day and methaemoglobin was found to be menced as the patient had become distressed by pain. present. 737
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on July 30, 2015
D. J. DALY, J. DAVENPORT AND M. C. NEWLAND
Department of Anaesthesia, The Queen Victoria Maternity Hospital, Adelaide, South Australia
738 CASE 3.
A primigravida, aged 18, attended the antenatal clinic regularly from the 20th week, her antenatal progress being uncomplicated. Labour commenced spontaneously at term on May 1, 1964, and lasted 30 hours. A continuous lumbar epidural block was used, the indication being inco-ordinate uterine action.
CASE 4.
A primigravida, aged 24. Her antenatal period was complicated by moderate pre-eclamptic toxaemia and hydramnios. Following two unsuccessful medical inductions with oxytocin drips the membranes were ruptured on May 20, 1964, and another oxytocin drip was started. Because of prolonged incoordinate labour and maternal distress a lumbar epidural block was commenced in the first stage.
The total dose of prilocaine was 790 mg. The patient became cyanosed after the last injection of prilocaine, remaining so for about 12 hours, and showing no improvement with the administration of oxygen. Spectroscopic examination of the mother's blood taken 1 hour after the onset of cyanosis showed the presence of methaemoglobin. CASE 6.
A primigravida, aged 26. This patient had an uncomplicated pregnancy. She was admitted on July 11, 1964, having had a slight show; membranes were intact and regular contractions were present. Progress was slow during the first stage because of inco-ordinate uterine action, and at 11.30 a.m. on July 13 a continuous lumbar epidural was begun. Details of continuous lumbar epidural analgesia. July 13, 11.30 a.m., 15 ml of 1 per cent prilocaine. Further doses were given on the same day as follows: 12.50 p.m., 15 ml; 4 p.m., 15 ml; 4.20 pjn. 5 ml; 5.25 p.m., 20 ml; 6.30 p.m. 20 ml. The total dose of prilocaine was 900 mg. At 7 p.m. cyanosis was first noticed. Two hours later she was given 10 ml of 1 per cent methylene blue intravenously over 5 minutes. Within half an hour the cyanosis had improved and a Caesarean section was commenced. The mother's blood remained dark throughout the operation but the baby cried soon after birth and showed no obvious cyanosis. A specimen of maternal blood, taken immediately before the administration of methylene blue, showed methaemoglobin on spectroscopic examination. CASE 7.
Details of continuous lumbar epidural analgesia. May 21, 12.40 a.m., 10 ml of 1 per cent prilocaine. Further doses were given as follows on the same day: 2 a.m., 10 ml; 3.30 a.m., 10 ml; 4.30 a.m., 20 ml; 6 a.m., 10 ml; 7 a.m., 10 ml; 8 a.m., 20 ml. At 9.30 a.m. a living male infant was delivered instrumentally. The total dose of 1 per cent prilocaine was 900 mg. At approximately 9.30 a.m. the patient appeared cyanosed. The cyanosis did not respond to oxygen and persisted for approximately 8 hours. A specimen of the mother's blood was taken 1 hour after the onset of cyanosis and found to be negative for methaemoglobin. CASE 5.
This patient, aged 27, had had a Caesarean section two years previously after a labour lasting three days. Her antenatal progress was uncomplicated, and the membranes were artificially ruptured at term on June 7, 1964. Labour commenced 7 hours later. The patient became extremely apprehensive and, in order to relieve pain, a continuous lumbar epidural block was started. Details of continuous lumbar epidural analgesia. June 7, 5.45 p.m., 10 ml of 1 per cent prilocaine. Further doses were given as follows on the same day: 6.45 p.m. 10 ml; 7.30 p.m. 10 ml; 8.15 p.m. 12 ml; 9.50 p.m. 20 ml; 10.50 p.m. 12 ml. Delivered with vacuum extractor of living female infant After delivery a further 5 ml of 1 per cent prilocaine were infiltrated into the perineum for repair of the episiotomy.
A primigravida, aged 20, had a pregnancy complicated by hydramnios and mild pre-eclamptic toxaemia. She was admitted on July 17, 1964, with a history of contractions at 5-minute intervals for 3 hours. There was no show and membranes were intact At 12.15 p.m. on July 18, because of slow progress in the first stage, a continuous lumbar epidural was begun. Details of continuous lumbar epidural analgesia. July 18. 12.15 p.m., 15 ml of 1 per cent prilocaine. Subsequent doses were given as follows: 1.45 pjn., 15 ml; 4.05 p.m., 15 ml; 7.45 p.m., 15 ml; July 19, 1 a.m., 10 ml; 2 a.m. 15 ml. The total dose of prilocaine was 850 mg. At 2 a.m. on July 19 the patient became cyanosed and was given 100 mg of vitamin C intramuscularly. This dose was repeated at 7 a.m. At 11 sum. on the same day the patient had a forceps delivery under general anaesthesia, the baby being resuscitated with some difficulty. The cyanosis persisted for a further hour after delivery. Blood was taken for methaemoglobin estimation at the time cyanosis was first apparent and was positive spectroscopicalry for methaemoglobin. DISCUSSION
Methaemoglobinaemia is a condition in which cyanosis occurs in the absence of cardiac or respiratory disease, due to the presence of excessive amounts of methaemoglobin in the blood. The majority of cases are due to exposure to nitxo or
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on July 30, 2015
Details of continuous lumbar epidural analgesia. May 1, 3.30 p.m., 10 ml of 1 per cent prilocaine given via lumbar epidural catheter. Further quantities of the same solution were given as follows: 5.45 pjn., 10 ml, 6.45 p.m,. 10 ml; 8.15 p.m., 10 ml; 9.45 p.m., 10 ml; 10.15 p.m., 10 ml; 11.15 p.m., 10 ml; May 2, 12.15 a.m., 10 ml; 2.35 a.m., 10 ml; 4.45 a.m., 10 ml; 6 ajn., 10 ml; 8.30 a.m., 10 ml. Forceps rotation and extraction were performed at full dilatation, resulting in delivery of a living female infant Cyanosis of the lips and fingers was noticed at 11.15 pjn. on May 1 after the sixth dose of prilocaine, Le. after a total dose of 500 mg. Blood taken soon after this revealed methaemoglobin on spectroscopic examination. The cyanosis persisted for some 12 hours.
BRITISH JOURNAL OF ANAESTHESIA
METHAEMOGLOBINAEMIA FOLLOWING THE USE OF PRILOCAINE
,CH2CH3
NH-CO-CH 2 -M \
CH 2 CH 3
Lignocaine
ADDENDUM
Since the compilation of this report, two further cases of confirmed methaemoglobinaemia have occurred following the use of 1 per cent prilocaine for epidural analgesia. This brings the number of cases showing cyanosis to nine out of a total of eighty-two cases who received 1 per cent prilocaine for this purpose. Previously, while using 1 per cent lignocaine, no cases of cyanosis were recognized out of a total of 360 blocks of this type. ACKNOWLEDGMENTS
Thanks are due to the Medical Superintendent of the Queen Victoria Maternity Hospital, Dr. L K. Furler, for much helpful advice and for permission to publish this report Also to Dr. R. N. Ibbotson of the Institute of Medical and Veterinary Science, Adelaide, for his help in the laboratory aspects of the investigation.
CH 3 REFERENCE
U
\
NH- CO-CH - NH-CH 2 CH 2 CH 3 CH3
Goodman, L. S., and Gilman, A. (1955). The Pharmacological Basis of Therapeutics, 2nd ed, p. 314. New York: Macmillan.
Prilocaine Fra. 1 Structural formulae of lignocaine and prilocaine.
The laboratory examination of the blood in these cases was done by means of a Hartridge reversion spectroscope. Though methaemoglobin was detected by this means in the blood of only five out of the seven cases showing cyanosis, it seems possible that it was the cause of the cyanosis in the remaining two cases. If this is so, the discrepancy may be due to lack of sensitivity in the spectroscopic examination, or perhaps to reduction of a significant amount of methaemoglobin between the time of taking the specimen of blood and of examining it in the laboratory. This preliminary report is submitted to bring to notice the possibility of methaemoglobinaemia following the use of prilocaine, a search of the literature having failed to reveal any reference to this matter. Further work is proceeding in this hospital with a view to clarifying the problem.
METHEMOGLOBINEMIB APRES USAGE DE PRILOCAINE (CrTANEST) SOMMAFRE
Une sdrie de quatre-vingt-et-un cas consecutifs ou un blocage Epidural lombaire continue a 6t6 realise1 chez des femmes en travail, est analyses. L'anesthesique utilise1 6tait la prilocaine (Citanest). Neuf cas presentaient une cyanose et dans sept de ces cas l'examen spectroscopique du sang montrait une me'the'moglobin^mie. Les rapports de la prilocaine avec certains derives de l'aniline connus pour provoquer de la me'the'moglobine'mie, sont discute's.
METHAMOGLOBINAMIE NACH ANWENDUNG VON PRILOCAINE (CITANEST) ZUSAMMENFASSUNO
Es wird Uber eine Serie von einundachtzig kreiflenden Frauen. bei denen eine kontinuierliche PeriduralanSsthesie im Lumbarbereich unter Verwendung von Prilocaine (Citanest) vorgenommen wurde. berichtet Bei neun Fallen wurde Zyanose beobachtet, bei sieben von diesen Fallen wurde bei der spektroskopischen Untersuchung des Blutes Methamoglobinamie festgestellt Die Verwandtschaft zwischen Prilocaine und den Anilinderivaten, von denen bekannt ist, dafi sie Methamoglobinamie verursachen, wird erwahnt.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on July 30, 2015
amino derivatives which are used extensively in industry for various purposes, e.g. in the synthesis of aniline dyes. The aniline derivatives acetanilide and acetophenetidin (phenacetin) are frequently incriminated (Goodman and Gilman, 1955). Lignocaine and prilocaine are related compounds (fig. 1), lignocaine being diethylamino -2, 6-dimethyl acetanilide, and prilocaine being a-n-propylamino 2-methyl-propionanilide.
739