Br. J. Surg. Vol. 62 (1975)471-473
General anaesthesia during early pregnancy LEO S T R U N I N , K . K N I G H T S . J . M . S T R U N I N A N D M I C H A E L E. WARD* SUMMARY
General anaesthesia in the early stages of pregnancy may carry an increased risk of embryotoxicity, One hundred and six women scheduled for non-emergency surgery were interviewed preoperatively and their menstrual history taken. Forty-three (41 per cent) were considered to be using adequate contraceptive therapy. Thirty-one (29 per cent) of the patients could have been in the early stages ofpregnancy, and of these women, 19 (61per cent) were undergoing surgery of a minor nature. Simple history taking identified the women ‘at risk’ and it is suggested that surgery could have been delayed without detriment in many cases.
IT is generally believed that anaesthesia and surgery during early pregnancy carry some risk of spontaneous abortion. The advice usually given, based on clinical experience, is that where surgery is necessary it should be delayed if possible until the second trimester. Animal studies (Smith et al., 1965; Fink et al., 1967) have shown that all the commonly used volatile anaesthetics can cause spontaneous abortion and fetal abnormalities when administered during early pregnancy. The concentrations used in these studies have always been of the order of those during general anaesthesia. Recently, concern has been expressed regarding a possible correlation between low concentrations of volatile anaesthetic agents in the atmosphere of operating areas and the incidence of spontaneous abortion and fetal abnormalities among female operating room personnel (Askrog and Harvald, 1970; Cohen et al., 1971 ; Knill-Jones et al., 1972). It should, however, be made clear that the evidence for this correlation is entirely circumstantial (Spence, 1973), and the effect of either low or anaesthetic concentrations of volatile anaesthetics in early pregnancy in humans is unknown. It seems that the greatest risk is probably during the early weeks of pregnancy (Shnider and Webster, 1965). It is not common practice to inquire into a woman’s menstrual history prior to general anaesthesia other than for gynaecological surgery. It may be, therefore, that women are exposed unnecessarily to potentially embryotoxic drugs during the earliest stages of pregnancy, indeed before pregnancy is diagnosed. The present study was undertaken to establish the population ‘at risk’ of undergoing general anaesthesia while pregnant .
Patients and methods One hundred and six women of childbearing age (1-5 years), scheduled for non-emergency surgery, excluding gynaecology, were visited by one of the
authors preoperatively (Table I ) . The patient’s menstrual history was taken and the following information obtained : I . Whether menstrual periods were regular or irregular. 2. The duration of each menstrual period. 3. The interval between menstrual periods. 4. The date of the last menstrual period. 5 . Whether they were taking oral contraceptives. 6. Whether there was any chance of pregnancy. In addition, the nature of the operation to be performed was recorded. Table I: PREGNANCY RISK GROUPS Groups Effective contraception Oral contraception Hysterectomy Tuba1 ligation Intra-uterine contraceptive device
No. of patients 32 6 4
%,
30 6 4
1
1
41 30 29
43 32 31
‘Pregnancy unlikely’ ‘Pregnancy possible’ Total
106
Table 11: INTERVAL BETWEEN CALCULATED DATE OF OVULATION AND GENERAL ANAESTHESlA IN ‘PREGNANCY POSSIBLE’ GROUP Interval: 10 wk 6-9 wk 4-5 wk 2-3 wk 10-13 d 5-9 d 1 4d
No of ptticnts: 2 1
2 4 4 3 14 Total
10*
* Pregnancy had been confirmed in I patient not included here.
Results Of the 106 women studied, 43 (41 per cent) were considered to be using adequate contraceptive therapy: 32 (30 per cent) were taking oral contraceptives; 6 (6 per cent) had had a hysterectomy; 4 (4 per cent) had had tuba1 ligation and 1 had an intra-uterine contraceptive device. Of the remaining 63 (59 per cent) patients, 32 (30 per cent) were calculated on the basis of their menstrual history to be between their last period and ovulation (‘pregnancy unlikely’ group). Thirty-one (29 per cent) patients were considered to be at risk (Table 11), since they were at a point in their menstrual cycle where they could have conceived prior to hospital admission (‘pregnancy possible’ group). * Department of Anaesthetics, King’s College Hospital and Medical School, London.
471
Leo Strunin et al. Table 111: SURGICAL PROCEDURES CARRIED OUT technique to exclude patients in the very earliest stages of pregnancy when the fetus may be at greatest risk Effective ‘Pregnancy ‘Pregnancy contrafrom anaesthetic agents. For this reason such urine Total unlikely’ possible’ Surgery ception testing was not carried out on patients in the present 35 6 11 Dental 18 study. Other more sensitive pregnancy tests such as 15 5 4 ENT 6 progesterone assay (Yousefnedjadian et al., 1972) or 2 4 14 Breast 8 human chorionic gonadotrophin assay (Wide, 1969) 12 7 2 3 Abdominal 11 are available and will give reliable results after the 5 3 Peripheral 3 7 Ophthalmic 2 seventh day following ovulation, but these techniques 5 EUA 1 are slow, expensive and restricted at present to a few 4 Thyroid 2 research centres. Table II shows that even these most Neuro2 __ 1 1 sensitive tests of pregnancy would leave more than 14 Thoracic (45 per cent) of the 31 patients in the ‘pregnancy Total 43 32 31 106 ~
On direct questioning, one of the ‘pregnancy possible’ patients was aware that she was pregnant, but she had reached 28 weeks’ gestation and was having an excision of a breast lump. Four other women conceded that they might be pregnant. For 5 patients it was 7 or more weeks since their last period, but of these, one was 15 years of age and her previous period had been her first; 2 others had only within the past 8 weeks terminated regular oral contraceptive therapy. A 27-year-old woman about to undergodentalextractions had waited 10 weeks since her last period and admitted concern that she might be pregnant. However, a pregnancy test performed within the past 5 days was negative. There were 5 other women where more than 4 weeks had elapsed since their last period; of these, one had been in hospital continuously during this time. Table 111shows the operative procedures carried out in the 106 women studied. It can be seen that of the 31 women in the ‘pregnancy possible’ group, 19 (61 per cent) were undergoing operations of a minor nature which could have been postponed.
Discussion We have been unable to find any authoritative statement in the world literature concerning the number of pregnant women undergoing anaesthesia. From our investigations, however, it seems clear that women who know or suspect that they may be pregnant have a natural anxiety concerning anaesthesia and surgery. Furthermore, 26 of the 106 women in our series could have been pregnant without being themselves aware of the fact. There are no absolute means of establishing beyond doubt whether or not these women were in the early stages of pregnancy, although more detailed questioning would probably have eliminated a proportion. There are, of course, a number of tests which may be applied. Of these, the Pregnosticon (Organon) or Gravindex (Ortho Pharmaceuticals Ltd) test is the simplest, involving the application of a drop of urine to a slide preparation. An answer, given by the presence or absence of agglutination, is available within 3 minutes. Unfortunately, although only few false positive results are produced there are generally an appreciable number of false negatives. In cases of pregnancy a reliable positive result will not be obtained until 4 weeks after ovulation. This will, therefore, preclude the use of this 472
possible’ group undetected at the time of anaesthesia and surgery. Therefore, routine testing for pregnancy would not, at present, identify the patients in the earliest stages after conception. Where some departure from a previously regular menstrual cycle draws attention to the possibility of pregnancy, one of the routine pregnancy tests should be carried out, and there may be a case for deferring surgery, where possible, until a conclusively negative result is obtained. It is regrettable that it is not common practice to ascertain a woman’s menstrual history prior to anaesthesia and surgery. It is clear that simple unembarrassing questions can identify a woman who may possibly be pregnant. Since many of the operative procedures were of a non-urgent simple nature, it would seem feasible to delay surgery until the potential risk of pregnancy had passed. An interesting point concerning the women taking oral contraceptives relates to their anxiety regarding taking their pills in relation to an operation. There seemed to be no clear advice as to whether they should take the pill in the immediate preoperative period and what should be done if they were unable to resume oral contraceptive therapy immediately postoperatively. Our gynaecological colleagues advise us that the correct management should be that where only 1 day is missed it can be compensated for by taking an additional tablet the following day. If 2 or more days are missed, then the advice should be to discontinue oral contraception for 5 days and then commence a new course. It is of course obvious that during the interval conception is possible. Despite the commonly held view that anaesthesia and surgery should not be carried out during the early stages of pregnancy, our study shows that a substantial number of women who could be pregnant are in fact put at risk. Simple history taking can identify these women, and again our study shows that many of them are scheduled for non-urgent surgical procedures. There may, therefore, be a good case, in the light of the existing evidence concerning embryotoxic effects of volatile anaesthetics, to delay surgery in these instances.
Acknowledgements The authors would like to thank their surgical colleagues for permission to interview their patients preoperatively, and Mr Julian Elias of the Department
General anaesthesia during early pregnancy
of Obstetrics and Gynaecology, King’s College Hospital, for help and advice. References
v. and HARVALD B. (1970) Teratogen effekt af inhalationanaestetika. Nord. Med. 83, 498-500. COHEN E. N., BELLVILLE J. w. and BROWN B. w. jun. (1971) Anesthesia, pregnancy, and miscarriage. A study of operating room nurses and anesthetists. Anesthesiology 35, 343-347. F I N K B. R., SHEPARD T. H. and BLANDAU R. J. (1967) Teratogenic activity of nitrous oxide. Nature (Lond.) 214, 146-148. KNILL-JONES R . P., RODRIGUES L. v., MOIR D. D. and SPENCE A. A. (1972) Anaesthetic practice and pregnancy. Controlled survey of women anaesthetists in the United Kingdom. Lancet 1, 13261328.
ASKROG
s. M. and WEBSTER G. M. (1965) Maternal and fetal hazards of surgery during pregnancy. Am. J. Obstet. Gynecol. 92, 891-900. SMITH B. E., GAUB M. L. and MOYA F. (1965) Investigations into the teratogenetic effects of anaesthetic agents : the fluorinated agents. Anesthesiology 26, 260-261. SPENCE A. A. (1973) Contamination of air by anaesthetics. Ann. R. Coll. Surg. Engl. 52, 360-361. WIDE L. (1969) Early diagnosis of pregnancy. Lancet 2, 863-864. YOUSEFNEDJADIAN E., FLORENSA E., COLLINS w. P. and SOMMERVILLE I. F. (1 972) Radio-immunoassay of 17-hydroxyprogesterone. J. Steroid Biochem. 3, 893-901. SHNIDER
473
General anaesthesia during early pregnancy LEO S T R U N I N , K . K N I G H T S . J . M . S T R U N I N A N D M I C H A E L E. WARD* SUMMARY
General anaesthesia in the early stages of pregnancy may carry an increased risk of embryotoxicity, One hundred and six women scheduled for non-emergency surgery were interviewed preoperatively and their menstrual history taken. Forty-three (41 per cent) were considered to be using adequate contraceptive therapy. Thirty-one (29 per cent) of the patients could have been in the early stages ofpregnancy, and of these women, 19 (61per cent) were undergoing surgery of a minor nature. Simple history taking identified the women ‘at risk’ and it is suggested that surgery could have been delayed without detriment in many cases.
IT is generally believed that anaesthesia and surgery during early pregnancy carry some risk of spontaneous abortion. The advice usually given, based on clinical experience, is that where surgery is necessary it should be delayed if possible until the second trimester. Animal studies (Smith et al., 1965; Fink et al., 1967) have shown that all the commonly used volatile anaesthetics can cause spontaneous abortion and fetal abnormalities when administered during early pregnancy. The concentrations used in these studies have always been of the order of those during general anaesthesia. Recently, concern has been expressed regarding a possible correlation between low concentrations of volatile anaesthetic agents in the atmosphere of operating areas and the incidence of spontaneous abortion and fetal abnormalities among female operating room personnel (Askrog and Harvald, 1970; Cohen et al., 1971 ; Knill-Jones et al., 1972). It should, however, be made clear that the evidence for this correlation is entirely circumstantial (Spence, 1973), and the effect of either low or anaesthetic concentrations of volatile anaesthetics in early pregnancy in humans is unknown. It seems that the greatest risk is probably during the early weeks of pregnancy (Shnider and Webster, 1965). It is not common practice to inquire into a woman’s menstrual history prior to general anaesthesia other than for gynaecological surgery. It may be, therefore, that women are exposed unnecessarily to potentially embryotoxic drugs during the earliest stages of pregnancy, indeed before pregnancy is diagnosed. The present study was undertaken to establish the population ‘at risk’ of undergoing general anaesthesia while pregnant .
Patients and methods One hundred and six women of childbearing age (1-5 years), scheduled for non-emergency surgery, excluding gynaecology, were visited by one of the
authors preoperatively (Table I ) . The patient’s menstrual history was taken and the following information obtained : I . Whether menstrual periods were regular or irregular. 2. The duration of each menstrual period. 3. The interval between menstrual periods. 4. The date of the last menstrual period. 5 . Whether they were taking oral contraceptives. 6. Whether there was any chance of pregnancy. In addition, the nature of the operation to be performed was recorded. Table I: PREGNANCY RISK GROUPS Groups Effective contraception Oral contraception Hysterectomy Tuba1 ligation Intra-uterine contraceptive device
No. of patients 32 6 4
%,
30 6 4
1
1
41 30 29
43 32 31
‘Pregnancy unlikely’ ‘Pregnancy possible’ Total
106
Table 11: INTERVAL BETWEEN CALCULATED DATE OF OVULATION AND GENERAL ANAESTHESlA IN ‘PREGNANCY POSSIBLE’ GROUP Interval: 10 wk 6-9 wk 4-5 wk 2-3 wk 10-13 d 5-9 d 1 4d
No of ptticnts: 2 1
2 4 4 3 14 Total
10*
* Pregnancy had been confirmed in I patient not included here.
Results Of the 106 women studied, 43 (41 per cent) were considered to be using adequate contraceptive therapy: 32 (30 per cent) were taking oral contraceptives; 6 (6 per cent) had had a hysterectomy; 4 (4 per cent) had had tuba1 ligation and 1 had an intra-uterine contraceptive device. Of the remaining 63 (59 per cent) patients, 32 (30 per cent) were calculated on the basis of their menstrual history to be between their last period and ovulation (‘pregnancy unlikely’ group). Thirty-one (29 per cent) patients were considered to be at risk (Table 11), since they were at a point in their menstrual cycle where they could have conceived prior to hospital admission (‘pregnancy possible’ group). * Department of Anaesthetics, King’s College Hospital and Medical School, London.
471
Leo Strunin et al. Table 111: SURGICAL PROCEDURES CARRIED OUT technique to exclude patients in the very earliest stages of pregnancy when the fetus may be at greatest risk Effective ‘Pregnancy ‘Pregnancy contrafrom anaesthetic agents. For this reason such urine Total unlikely’ possible’ Surgery ception testing was not carried out on patients in the present 35 6 11 Dental 18 study. Other more sensitive pregnancy tests such as 15 5 4 ENT 6 progesterone assay (Yousefnedjadian et al., 1972) or 2 4 14 Breast 8 human chorionic gonadotrophin assay (Wide, 1969) 12 7 2 3 Abdominal 11 are available and will give reliable results after the 5 3 Peripheral 3 7 Ophthalmic 2 seventh day following ovulation, but these techniques 5 EUA 1 are slow, expensive and restricted at present to a few 4 Thyroid 2 research centres. Table II shows that even these most Neuro2 __ 1 1 sensitive tests of pregnancy would leave more than 14 Thoracic (45 per cent) of the 31 patients in the ‘pregnancy Total 43 32 31 106 ~
On direct questioning, one of the ‘pregnancy possible’ patients was aware that she was pregnant, but she had reached 28 weeks’ gestation and was having an excision of a breast lump. Four other women conceded that they might be pregnant. For 5 patients it was 7 or more weeks since their last period, but of these, one was 15 years of age and her previous period had been her first; 2 others had only within the past 8 weeks terminated regular oral contraceptive therapy. A 27-year-old woman about to undergodentalextractions had waited 10 weeks since her last period and admitted concern that she might be pregnant. However, a pregnancy test performed within the past 5 days was negative. There were 5 other women where more than 4 weeks had elapsed since their last period; of these, one had been in hospital continuously during this time. Table 111shows the operative procedures carried out in the 106 women studied. It can be seen that of the 31 women in the ‘pregnancy possible’ group, 19 (61 per cent) were undergoing operations of a minor nature which could have been postponed.
Discussion We have been unable to find any authoritative statement in the world literature concerning the number of pregnant women undergoing anaesthesia. From our investigations, however, it seems clear that women who know or suspect that they may be pregnant have a natural anxiety concerning anaesthesia and surgery. Furthermore, 26 of the 106 women in our series could have been pregnant without being themselves aware of the fact. There are no absolute means of establishing beyond doubt whether or not these women were in the early stages of pregnancy, although more detailed questioning would probably have eliminated a proportion. There are, of course, a number of tests which may be applied. Of these, the Pregnosticon (Organon) or Gravindex (Ortho Pharmaceuticals Ltd) test is the simplest, involving the application of a drop of urine to a slide preparation. An answer, given by the presence or absence of agglutination, is available within 3 minutes. Unfortunately, although only few false positive results are produced there are generally an appreciable number of false negatives. In cases of pregnancy a reliable positive result will not be obtained until 4 weeks after ovulation. This will, therefore, preclude the use of this 472
possible’ group undetected at the time of anaesthesia and surgery. Therefore, routine testing for pregnancy would not, at present, identify the patients in the earliest stages after conception. Where some departure from a previously regular menstrual cycle draws attention to the possibility of pregnancy, one of the routine pregnancy tests should be carried out, and there may be a case for deferring surgery, where possible, until a conclusively negative result is obtained. It is regrettable that it is not common practice to ascertain a woman’s menstrual history prior to anaesthesia and surgery. It is clear that simple unembarrassing questions can identify a woman who may possibly be pregnant. Since many of the operative procedures were of a non-urgent simple nature, it would seem feasible to delay surgery until the potential risk of pregnancy had passed. An interesting point concerning the women taking oral contraceptives relates to their anxiety regarding taking their pills in relation to an operation. There seemed to be no clear advice as to whether they should take the pill in the immediate preoperative period and what should be done if they were unable to resume oral contraceptive therapy immediately postoperatively. Our gynaecological colleagues advise us that the correct management should be that where only 1 day is missed it can be compensated for by taking an additional tablet the following day. If 2 or more days are missed, then the advice should be to discontinue oral contraception for 5 days and then commence a new course. It is of course obvious that during the interval conception is possible. Despite the commonly held view that anaesthesia and surgery should not be carried out during the early stages of pregnancy, our study shows that a substantial number of women who could be pregnant are in fact put at risk. Simple history taking can identify these women, and again our study shows that many of them are scheduled for non-urgent surgical procedures. There may, therefore, be a good case, in the light of the existing evidence concerning embryotoxic effects of volatile anaesthetics, to delay surgery in these instances.
Acknowledgements The authors would like to thank their surgical colleagues for permission to interview their patients preoperatively, and Mr Julian Elias of the Department
General anaesthesia during early pregnancy
of Obstetrics and Gynaecology, King’s College Hospital, for help and advice. References
v. and HARVALD B. (1970) Teratogen effekt af inhalationanaestetika. Nord. Med. 83, 498-500. COHEN E. N., BELLVILLE J. w. and BROWN B. w. jun. (1971) Anesthesia, pregnancy, and miscarriage. A study of operating room nurses and anesthetists. Anesthesiology 35, 343-347. F I N K B. R., SHEPARD T. H. and BLANDAU R. J. (1967) Teratogenic activity of nitrous oxide. Nature (Lond.) 214, 146-148. KNILL-JONES R . P., RODRIGUES L. v., MOIR D. D. and SPENCE A. A. (1972) Anaesthetic practice and pregnancy. Controlled survey of women anaesthetists in the United Kingdom. Lancet 1, 13261328.
ASKROG
s. M. and WEBSTER G. M. (1965) Maternal and fetal hazards of surgery during pregnancy. Am. J. Obstet. Gynecol. 92, 891-900. SMITH B. E., GAUB M. L. and MOYA F. (1965) Investigations into the teratogenetic effects of anaesthetic agents : the fluorinated agents. Anesthesiology 26, 260-261. SPENCE A. A. (1973) Contamination of air by anaesthetics. Ann. R. Coll. Surg. Engl. 52, 360-361. WIDE L. (1969) Early diagnosis of pregnancy. Lancet 2, 863-864. YOUSEFNEDJADIAN E., FLORENSA E., COLLINS w. P. and SOMMERVILLE I. F. (1 972) Radio-immunoassay of 17-hydroxyprogesterone. J. Steroid Biochem. 3, 893-901. SHNIDER
473
