A FURTHER STUDY OF GENERAL ANAESTHESIA FOR CAESAREAN SECTION

Br.J. Anaesth. (1976), 48, 661

A FURTHER STUDY OF GENERAL ANAESTHESIA FOR CAESAREAN SECTION J. S. CRAWFORD, F. M. JAMES HI, P. DAVIES AND M. CRAWLEY SUMMARY

A previous study (Crawford and Davies, 1975) was concerned with a comparison of the effects upon mother and infant of 0.1% methoxyflurane and 0.1% trichloroethylene for maintenance of anaesthesia. Neither drug caused neonatal depression, and the incidence of maternal nausea, vomiting and headache following anaesthesia was not influenced by the choice of agent. The incidence of awareness plus unpleasant dreams was greater when trichloroethylene had been used. However, the incidence of these unpleasant complications was disappointingly high with each technique, and we have undertaken a similar investigation using 0.2% of the volatile agent, in the hope of reducing the incidence of awareness without increasing the incidence of neonatal depression and of other maternal complications. PATIENTS AND METHODS

The technique of anaesthesia was identical to that described by Crawford and Davies (1975), except for the concentration in which the volatile agent was administered: each patient (including those about to undergo elective section) received at least two doses of Mist, magnesium trisilicate (B.P.C.) 15 ml before the start of anaesthesia. None of the patients lay supine during the hour or more preceding operation, J. SELWYN CRAWFORD, F.F.A.R.C.S.; MARGARET CRAWLEY,

B.SC, Birmingham Maternity Hospital, Queen Elizabeth Medical Centre, Edgbaston, Birmingham, B15 2TG. FRANCIS M. JAMES HI, M.D., Department of Anesthesiology,

Bowman Gray School of Medicine, Winston Salem, North Carolina, U.S.A. PAUL DAVIES, PH.D., Department of Mathematical Statistics, University of Birmingham.

and upon being transferred to the operating table, each patient was tilted laterally, on a wedge, towards the side at which the surgeon would stand. Dextrose 5% in water was infused i.v. and the patient breathed 100% oxygen for 4-5 min before induction of anaesthesia. Cricoid pressure was applied by an assistant. Hyoscine 0.6 mg was given i.v., followed by thiopentone 250-300 mg (2.5% solution) and suxamethonium 100 mg. After endotracheal intubation, anaesthesia was maintained using IPPV with a mixture of nitrous oxide (4 litre/min) in oxygen (8 litre/min) and 0.2% (v/v) of the volatile agent, with the aid of a Howell ventilator, until the infant was delivered. Following delivery the flow rates of nitrous oxide and oxygen were reversed. Neuromuscular block was maintained by the infusion of a solution of suxamethonium 1 mg/ml. Arterial blood was sampled from the mother at the time of delivery (MA). A loop of umbilical cord was double-clamped at the time of delivery, and samples of umbilical vein (UV) and umbilical artery (UA) blood were withdrawn immediately. All blood samples were taken into heparinized syringes. The oxygen tension, oxygen saturation, haematocrit and acid-base parameters were estimated using, where appropriate, the Astrup (Radiometer) apparatus, an oxygensaturation meter (Radiometer O.S.M. 1) and applying the Siggaard-Andersen nomogram. The Apgar-minus-colour score of each infant was assessed at 1 ((A-C) x ) and 5 min ((A-C) 5 ) after complete delivery of the infant. The time between induction of anaesthesia and deb'very of the infant, to the nearest minute, was recorded (I-D interval), as

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Methoxyflurane or trichloroethylene in concentrations of 0.2% or 0.1% used in anaesthesia for Caesarean section were compared. There were no differences in the acid-base state or the clinical condition of the infant at delivery, or in the incidence of maternal complications, which could be related to the choice of volatile agent. Either volatile agent in the 0.2% concentration was associated with an overall incidence of maternal awareness and unpleasant dreams of 2.5%, compared with 4.9% when the 0.1% concentration was used. The incidence of maternal nausea and vomiting was less in the 0.2% series. There was an apparent relationship between the induction-delivery interval and (a) the degree of neonatal acidosis and (b) the Apgar-minus-colour scores at one minute ((A —C),). The correlation between those indices of increasing foetal depression and increasing length of the uterine incision-delivery interval was highly significant. There was no systematic relationship between the one-minute score for "colour" and the umbilical artery Po 2 .

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There were two groups of patients undergoing elective section—A: patients whose pregnancy had advanced beyond 36 completed weeks, and in whom there was no suspected placental dysfunction; B: the remaining patients. Analyses of the neonatal responses to the two techniques of anaesthesia are confined to Group A patients. Analyses of the maternal sequelae apply to the entire series—elective plus all emergency operations. There were 358 patients in the study; 126 of these underwent elective section, 78 in Group A (table I). RESULTS

Maternal responses

Awareness and dreaming (table II). The combined incidence of awareness and unpleasant dreams among the patients undergoing elective section in the 0.2% methoxyflurane series was twice that recorded in the 0.1% series, but the incidence in the 0.2% trichloroethylene series was half of that in the 0.1% trichloroethylene series. However, in the two series of emergency section, the incidence of awareness plus unpleasant dreams was almost zero when 0.2% of the

TABLE I. Number of subjects in each of the groups analysed 0.2% methoxyflurane Elective section groups A + B (total) Group A elective available for (A — C) score analyses Group A elective5 all biochemical values disregarding MA Group A elective available for correlating UA Po 2 values with 1-min score for colour Emergency section

0.2% trichloroethylene

66

60

42

36

24

20

27

22

142

90

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was the time (s) between incision of the myometrium and delivery of the infant (U-D interval). On the day after operation, each mother was asked whether or not she had experienced nausea, vomiting or headache since recovering from the anaesthetic. No attempt was made to differentiate, as in the previous study, between "immediate" and "subsequent" nausea and vomiting. Each patient was asked also whether she had any recollection of the events occurring during operation, or had experienced pleasant or unpleasant dreams whilst under the anaesthetic. The patients underwent either elective or emergency Caesarean section, the former being defined as applying to a patient whose membranes were intact and who was not in established labour, irrespective of the urgency of the procedure. The majority of patients undergoing elective section received chlordiazepoxide 20 mg orally 1-2 h before operation. The majority of the patients who underwent emergency section had received extradural analgesia- during labour, the remainder having received either no analgesia or a small quantity of conventional analgesia.

TABLE II. Awareness (A) unpleasant dreams (UPD) and pleasant dreams (PD) occurring in a previous study (0.1%) (Crawford and Davies, 1975) and in the current series. The percentages refer to the combined incidence of A plus UPD 0.1% methoxyflurane Elective section

Emergency section All sections

n A UPD PD n

A UPD PD n

A UPD PD

73

78

2 } 3.8% 0 92 2\~

0.1% trichloroethylene

J J-11.0%

0.2% methoxyflurane 66 4

60

7.6%

0' 142

85 00/

).7%

1J • '"

2

170 2

158 9

6.3%

0.2% trichloroethylene

208 5

2.9%

90 0 0 2 150 2

2.0%

663

GENERAL ANAESTHESIA FOR CAESAREAN SECTION

TABLE III. Nausea (AT), vomiting (V) and headache (H) during thefirst24 h after Caesarean section in the four anaesthetic groups 0.1% methoxyflurane

0.1% trichloroethylene

0.2% methoxyflurane

0.2% trichloroethylene

n N V H

78 10 7 0

73 13 7 0

66 3 0 1

60 1 1 0

Emergency section

n N V

92 20 11 1

85 16 6 2

142 9 6 2

90 6 1 1

All sections

n N V H

170 30

158 29

208 12

150 7

H

18 (10.6%) 1

13 (8.2%) 2

volatile agent was provided. Only two of the patients who received the volatile agent in 0.2% concentration recalled having felt pain or discomfort. Nausea, vomiting and headache (table III). The incidence of nausea and vomiting during the first 24 h after operation was less in each of the 0.2% series than in the 0.1% series. The incidence of headache after operation was very small.

6 (2.9%)

2(1.3%)

3

1

TABLE IV. Mean values and SEM {brackets) of pH (units), base excess (BE) (mmol/litre) and Pco 2 (mm Hg) for two groups of patients undergoing elective Caesarean section and receiving either 0.2% methoxyflurane or 0.2% trichloroethylene 0.2% methoxyflurane (n = 24)

7.464 PH -2.2 BE 27.4 Pco 2 Maternal-foetal acid-base relationships and clinical UA 7.320 pH condition of the neonate -1.0 BE Biochemistry. The mean acid-base parameters 50.1 Pco 2 (table IV) of the two groups were similar. There were UV 7.383 PH no statistically significant differences between the BE - 1 . 2 groups for any of the variables related to MA, UA, 39.8 Pco 2 UV and the transplacental gradients. MA-UA PH 0.144 -1.2 BE Correlations were sought between these variables Pco 2 -22.7 and the I-D and U - D intervals, and, in the four MA-UV 0.080 PH groups of cases (each percentage of the two volatile -1.0 BE agents), were found to exhibit general similarity in Pco 2 -12.4 respect of sign but some variability in magnitude. A I-D (min) 14.7 linear regression analysis of variance of these sets of U-D (s) 84.3

correlations revealed no significant difference between the four groups, and the relationships could therefore be represented by pooled correlations (table V). Examination of the common correlations shows a tendency for an increasing length of I-D interval to be associated with an increasing degree of maternal and foetal acidosis. This reaches the level of statistical significance only in respect to UA pH and base excess and UV base excess, and is not seen in respect of the values referable to transplacental gradients. Substantial and consistent correlations do emerge, however, in respect of the U-D interval. Clinical condition of the neonate. Five infants (two in the 0.2% trichloroethylene series and three in the 55

(0.009) (0.4) (0.8) (0.007) (0.4) (1.3) (0.007) (0.4) (1.0) (0.009) (0.3) (1.4) (0.007) (0.3) (0.9) (0.9) (10.4)

MA

0.2% trichloroethylene (n = 20) 7.461 -2.6 26.8 7.317 -0.8 51.2 7.370 -1.3 41.3 0.144 -1.8 -24.5 0.091 -1.3 -14.5 14.1 78.1

(0.010) (0.4) (0.9) (0.007) (0.4) (1.4) (0.007) (0.4) (1.1) (0.009) (0.4) (1.5) (0.008) (0.3) (1.0) (1.0) (11.4)

0.2% methoxyflurane series of Group A elective sections) had deficient Apgar-minus-colour scores at 5 min. In four of these a large quantity of fluid was aspirated from the upper airway, three of the infants having been delivered by the breech. The details of the intervals are as follows, from which it will be observed that no striking pattern emerges: (A-C) 5 I - D (min) U - D (s) 0.2% trichloroethylene 0.2% methoxyflurane

5 7 7 2 4

14 24 23 13 15

150 78 135 44 255

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Elective section

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TABLE V. Correlation coefficient for maternal arterial and cord blood pH, base excess (BE) and Pco2 and the induction-delivery (I-D) and uterine incision-delivery (U-D) intervals in 101 patients undergoing elective Caesarean section I-D interval Acid-base variable

Pooled correlation

U-D interval

P level at which significantly Pooled different from zero correlation

-0.18 -0.19 0.04

UA

pH BE Pco,,

-0.27 -0.24 0.15

<0.01 <0.02

XJV

pH BE •Pco2

-0.18 -0.29 0.01

<0.01

MA-UApH BE Pco 2 MA-UVpH BE Pco 2

0.05 -0.15 -0.24

<0.02

-0.46 -0.36 0.42

< 0.001 < 0.001 < 0.001

-0.15 -0.24 0.04

<0.02

0.04 0.08 -0.12

0.44 0.27 -0.54

< 0.001 <0.01 < 0.001

-0.05 0.16 0.02

0.21 0.14 -0.24

<0.05

Because of this, and because of the overwhelming number of "perfect" (A—C)5 scores, no further analysis of these data was undertaken. We compared the ( A - C ^ data from the 0.2% concentration groups in respect to the duration of the I-D interval (table VI). As this revealed no striking

TABLE VII. Distribution of "perfect" and "imperfect" \-min Apgar-minus-colour scores in the four series (defined with reference to the choice of volatile agent and to the concentration in which it was administered) related to the duration of the induction-delivery intervals grouped as equal to or less than 15 min and more than 15 min Methoxyflurane

TABLE VI. Incidence of Apgar-minus-colour scores in the two 0.2% concentration series, related to the induction-delivery interval 0.2% methoxyflurane

0.2% trichloroethylene

6-10 11-15 16-20

20 +

<7

<7

5 13 10 3

0 4 1 1

4 14 7 3

contrast we grouped the cases into "perfect" (8) and "imperfect" (<8) (A—C)x scores, and into those with I-D interval of less than or equal to 15 min and those with an I-D interval greater than 15 min. We included in these analyses the two series of 0.1% concentration reported previously (table VII). There was no statistically significant difference between the percentage of imperfect scores in each of the four

Trichloroethylene (A-C),

I-D (min)

<8

<8

8

0.1%

4 17

13 21

19 18

0.2%

4 7

18 13

18 10

(AI-D (min)

<0.02

groups whose I-D interval was ^ 1 5 min, and no statistically significant difference between the percentage of imperfect scores in each of the four groups in which the I-D interval exceeded 15 min. Therefore the data from the four groups were pooled and a similar comparison was made. This showed that 35.4% of the I-D > 15 min group had imperfect scores compared with 21.8% of the I-D < 15 min group. Application of the Chi-square test reveals that there is statistically significant evidence of an association between I-D interval and (A— C)1 score at the P<0.08 probability level.

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pH BE Pco 2

MA

P level at which significantly different from zero

665

GENERAL ANAESTHESIA FOR CAESAREAN SECTION The relationships between (A—C)x scores and the U-D intervals were examined in a similar manner (tables VIII and IX). The percentage of imperfect scores appeared to be little affected by the choice of volatile agent. Analysis of the pooled data from the four groups (table IX) revealed significant evidence of an association between a high U-D interval and an imperfect ( A - C ) x score (P< 0.001). Of those with a U-D interval less than 90s, 17.8% had imperfect

(A— C)x scores, compared with 46.3% of those with a U-D greater than 90 s. Neither in the 0.2% methoxyflurane series nor in the 0.2% trichloroethylene series was there a suggestion of an association between the percentage value of oxygen saturation in umbilical artery blood and the points allotted for "colour" in the original 1-min Apgar score (table X).

TABLE V I I I . Distribution of Apgar-minus-colour scores at 1 min within the two 0.2% concentration series, related to the uterus incision-delivery interval groups in cohorts of 30 s

The mother The total incidence of awareness plus unpleasant dreams has been reduced by increasing the concentration of trichloroethylene, but the effect of increasing the concentration of methoxyflurane was small. It seems unlikely that these complications will be totally eliminated from any large series of patients to whom 67% oxygen is administered, without posing a formidable threat of drug-induced depression of the neonate. We prefer to provide 67% oxygen because this has been shown to be associated with optimal results in respect to the clinical condition, acid-base status and respiratory gas tensions of the neonate (Rorke, Davey and Du Toit, 1968; Marx and Mateo, 1971), and we have presented evidence of its superiority to 50% oxygen in this regard (Crawford, Burton and Davies, 1973). Coleman and Downing (1975) have recently reported a zero incidence of awareness during anaesthesia for elective Caesarean section when enflurane (0.5-0.8%) was used for maintenance of anaesthesia. However, their patients received a 50% mixture of nitrous oxide in oxygen, and as they studied only 50 patients, a 2% incidence of awareness would have involved one patient only. It is difficult to explain the difference in the incidence of awareness plus unpleasant dreams related to the circumstances of the Caesarean section, as the majority of patients who underwent emergency section had not received a depressant drug during labour and the patients were not exhausted by prolonged or painful labour. Only rarely had a patient undergoing emergency Caesarean

DISCUSSION

Trichloroethylene

(A-C) x

U-D (s)

<7

0-30 31-60 61-90 91-120 121-150 151-180 181-210

0 2 1 2 1 0 0 1

211 +

<7 0 1 0 1 1 1 0 0

1 11 12 4 2 1 0 0

0 1 2 1 2 0 0 0

0 0 2 0 0 0 0 0

3 8 9 5 2 1 0 0

TABLE IX. Distribution of "perfect" and "imperfect" 1-min Apgar-minus-colour scores among the four series (defined with reference to the choice of volatile agent and to the concentration in which it was administered) related to the duration of the uterine incision—delivery intervals groups as equal to or less than 90 s and more than 90 J

Methoxyflurane

Trichloroethylene

(A-C),

0.1% 0.2%

U-D (s)

<8

8

<8

8

<90 >90 ^90 >90

7 14 4 7

29 5 24 7

7 1 5 3

33 9 20 8

TABLE X. Mean values Po2 (mm Hg) of umbilical,artery blood grouped according to the volatile agent provided and to the score allotted for colour at 1 min

Score for colour

0.2% methoxyflurane 0.2% trichloroethylene

Frequency Mean UA Po 2 Frequency Mean UA Po2

0

1

2

7 25.1 4 22.7

17 23.6 16 25.5

3 28.0 2 21.5

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Methoxyflurane

666

The infants Our data suggest that the clinical condition of the infant at the time of delivery (A—C scores) is not influenced by the choice of volatile agent or the concentration used in the technique which we have employed. The acid-base state of the infant at delivery was unrelated to these factors. It is likely that the observation reported previously (Crawford and Davies, 1975), that MA, UA and UV samples in the 0.1% trichloroethylene series were significantly less acidotic than were those from the 0.1% methoxyflurane series (whilst the values referable to the transplacental gradients did not differ significantly), was a chance finding. We were able to pool the data from the four groups in order to examine the relationships between the two intervals and each of the indices of infant well-being. There appears to be a tenuous relationship between the acid-base state of the infant and the duration of the I-D interval, and the (A— C) 1 score. However, we have confirmed that the duration of the U-D interval is the major determinant of the neonatal state during elective Caesarean section conducted under the regimen described; the direct relationship between an increasing length of the U-D interval and an increasing degree of neonatal acidosis is highly significant, and is reflected in the significant relationship found to exist between a prolonged U-D interval and an "imperfect" (A—C)x score. Although we have stated previously (Crawford, Davies and Pearson, 1973) that the points allotted for "colour" in the original Apgar score provided no indication of the acid-base state of the infant, we

observed a significant relationship between the oxygen saturation in umbilical artery blood and the 1-min score for colour in the 0.1% methoxyflurane series (Crawford and Davies, 1975). This association between the two variables has not been confirmed in the present study. ACKNOWLEDGEMENTS

Our thanks are due to the several members of the Anaesthetic staff of the hospital who were responsible for the care of the mothers who comprised the series, and to members of the technical staff of the Clinical Chemistry Department who helped with the biochemical analyses. Financial support was provided by the Medical Research Endowment Fund Committee of the United Birmingham Hospitals, to whom thanks are given. REFERENCES

Coleman, A. J., and Downing, J. W. (1975). Enflurane anesthesia for Caesarean section. Anesthesiology, 43, 354. Crawford, J. S., Burton, M., and Davies, P. (1973). Anaesthesia for section: further refinements of a technique. Br. J. Anaesth., 45, 726. Crawford, J. S., and Davies, P. (1975). A return to trichloroethylene for obstetric anaesthesia. Br. J, Anaesth., 47, 482. Pearson, J. F. (1973). Significance of the individual components of the Apgar score. Br. J. Anaesth., 45, 148. Marx, G. F., and Mateo, C. V. (1971). Effects of different oxygen concentrations during general anaesthesia for elective Caesarean section. Can. Anaesth. Soc.J., 18,587. Rorke, M. J., Davey, D. A., and Du Toit, H. J. (1968). Foetal oxygenation during Caesarean section. Anaesthesia, 23, 585. ETUDE COMPLEMENTAIRE SUR L'ANESTHESIE GENERALE POUR LES OPERATIONS CESARIENNES RESUME

On a compare le methoxyflurane ou le trichloroethylene, en concentrations a 0,2% ou a 0,1%, utilise pour l'anesthesie lors des operations cesariennes. On n'a constate aucune difference dans l'etat acide/base ou l'etat clinique de l'enfant au moment de l'accouchement, ou dans Pincidence des complications maternelles, qui soit susceptible d'etre reliee au choix de l'agent volatil. L'un ou l'autre de ces agents volatils, en concentration a 0,2%, a ete associe a une incidence de la conscience maternelle et a des cauchemars dans 2,5% des cas, par rapport a 4,9% des cas, lorsqu'on a utilise la concentration a 0,1%. L'incidence des nausees maternelles et des vomissements a ete moindre dans la serie des concentrations a 0,2%. II y a eu une relation apparente entre Pintervalle induction-accouchement et (a) le degre d'acidose du nouveau-ne et (b) les indices d'Apgar moins couleur a une minute (A —C),. La correlation entre ces indices de depression croissante du foetus et la longueur croissante de l'intervalle de l'accouchement par incision uterine a ete hautement significative. II n'y a eu aucune relation systematique entre l'indice d'une minute pour la couleur et la tension en oxygene (Po2) de l'artere ombilicale.

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section received a total dose of pethidine in excess of 200 mg, and it is unlikely that MA Pco 2 was significantly less during operation than that recorded in the elective cases. However, the mothers who required emergency section were more tired than were those who underwent elective section. As only two (0.6%) of the patients in the combined 0.2% series recollected discomfort during operation, we are reluctant to advise an increase in the depth of anaesthesia to reduce the incidence of these complications. We have no satisfactory explanation of the marked reduction in the incidence of postoperative nausea and vomiting associated with the higher concentration. The number of patients who were given perphenazine (Stemetil) in the recovery room was the same in both the 0.1% and the current series. It is apparent that headache after operation is not a feature of the two volatile anaesthetic agents under review.

BRITISH JOURNAL OF ANAESTHESIA

GENERAL ANAESTHESIA FOR CAESAREAN SECTION EINE WEITERE STUDIE DER ALLGEMEINEN NARKOSE FOR KAISERSCHNITT ZUSAMMENFASSUNG

AMPLIACION DE ESTUDIO DE LA ANESTESIA GENERAL EN LA OPERACION CESAREA SUMARIO

Se compararon metoxiflurano o tricloroetileno en concentraciones del 0,2% o del 0,1% como anestesicos usados en la operation cesarea. No hubo diferencias en el equilibrio acido-base o en el estado clinico del neonato en el alumbramiento, o en la frecuencia de complicaciones maternas, que pudieran ser atribuidas a la election de substancia volatil. Cualquiera de ellas a la concentracion del 0,2% estuvo asociada con una frecuencia general del 2,5% de conciencia maternal y suefios desagradables, en comparacion con el 4,9 % cuando se uso la concentracion del 0,1 %. La frecuencia de nauseas y vomitos maternos fue menor en la serie al 0,2%. Hubo una aparente relacion entre el intervalo induccion-alumbramiento y (a) el grado de acidosis neonatal y (b) los tanteos a un minuto de la escala Apgar menos la cifra para el color (A —C)^ La correlation entre aquellos indices de creciente depresion fetal y creciente valor del intervalo incision uterina-alumbramiento fue altamente significante. No hubo ninguna relacion sistematica entre el tanteo a un minuto para el "color" y la Po 2 en la arteria umbilical.

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Methoxyfluran oder Trichloroathylen in Konzentrationen von 0,2% oder 0,1% wurden in der Verwendung fur Narkose bei Kaiserschnitt untersucht. Es gab keine Unterschiede im Saurebasis-Status oder in der klinischen Verfassung des Kindes bei der Geburt, noch in der Haufigkeit von Komplikationen bei der Mutter, Unterschiede, die auf die Wahl des einen oder anderen Mittels zuriickgefuhrt werden konnten. Bei jedem Mittel in der Konzentration von 0,2% ergaben sich bei 2,5% Auftreten von Bewusstwerden der Mutter und von unangenehmen Traumen, verglichen mit solchen Erscheinungen bei 4,9%, wenn eine Konzentration von 0,1% verwendet wurde. Bei Konzentrationen von 0,2% waren Brechreiz und Erbrechen bei den Muttern weniger haufig. Es bestand eine offenbare Verbindung zwischen dem Einleitungs- bis Geburt-Intervall und (a) dem Ausmass der neonatalen Azidose und (b) dem Apgar-minus-Farbresultat nach einer Minute (A —C)^ Die Wechselbeziehung zwischen diesen Resultaten von wachsender fotaler Depression und wachsender Lange des Intervalls von Schnitt bis Geburt war von hochster Bedeutung. Es bestand eine systematische Beziehung zwischen dem einminiitigen

667