Supplementary oxygen for elective Caesarean section under spinal anaesthesia: useful in prolonged uterine incision-to-delivery interval?{dagger}

K. S. Khaw*,1, W. D. Ngan Kee1, A. Lee1, C. C. Wang2, A. S. Y. Wong1, F. Ng1 and M. S. Rogers2

1 Department of Anaesthesia and Intensive Care and 2 Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China

*Corresponding author: Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China. E-mail: KimKhaw@cuhk.edu.hk
{dagger}Presented as a poster at The South African Society of Anaesthesiologists Congress, Sun City, South Africa, 14–20 March 2003.

Accepted for publication: November 14, 2003


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Background. The benefit of administering supplementary oxygen during elective Caesarean section under regional anaesthesia is controversial. It has been hypothesized that its use would improve fetal oxygenation in the event of a prolonged uterine incision-to-delivery (U–D) interval. Our aim was to test this hypothesis in a prospective, randomized, double-blinded, controlled study.

Methods. We allocated randomly 204 women having elective Caesarean section under spinal anaesthesia to breathe 21, 40 or 60% oxygen. We recorded the U–D interval, umbilical arterial (UA) and venous (UV) blood gases and oxygen content and Apgar scores. Subgroup analysis was performed according to whether the U–D interval was prolonged (>180 s) or not.

Results. The U–D interval was <180 s in 159 patients and >180 s in 45 patients. There were no differences in UV or UA blood gases, oxygen content or Apgar scores between cases with and without a prolonged U–D interval. In cases without a prolonged U–D interval, administering 60% oxygen increased UV PO2 (mean 4.3 (SD 1.1) vs 3.7 (1.0) kPa, P=0.003) and oxygen content (14.4 (3.3) vs 12.9 (2.7) ml dl–1, P=0.007) compared with air. In cases with a prolonged U–D interval, administering 60% oxygen increased UV PO2 (4.6 (0.6) vs 3.9 (0.8) kPa, P=0.019) compared with air but there was no difference in UV oxygen content. There was no increase in the UV PO2 or oxygen content when 40% oxygen was administered compared with air.

Conclusions. Supplementary oxygen did not increase fetal oxygenation in cases where the U–D interval was prolonged. Our data do not support the routine administration of supplementary oxygen during elective Caesarean section for this purpose.

Br J Anaesth 2004; 92: 518–22

Keywords: anaesthesia, obstetric; anaesthetic techniques, subarachnoid; complications, acidosis; oxygen, supplementary; statistics, Apgar scores; surgery, Caesarean section; surgery, uterine incision to delivery


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The benefit of administering supplementary oxygen during elective Caesarean section under regional anaesthesia is controversial.1 Previously, we showed that when mothers breathed 60% oxygen compared with air, the umbilical venous (UV) partial pressure of oxygen (PO2) was modestly increased. However, this was at the expense of increased lipid peroxidation in mother and fetus, indicating that hyperoxygenation may not be completely without harm.2 With the ability to monitor maternal oxygenation easily using peripheral pulse oximetry, many anaesthetists have ceased the routine provision of oxygen in uncomplicated cases.1 This may be appropriate in elective Caesarean sections because they are low-risk procedures in which fetal outcome is expected to be favourable. Unpredictably, however, the uterine incision-to-delivery (U–D) interval may sometimes be prolonged, which has been associated with fetal acidosis.3 4 In these cases, it has been suggested that supplementary oxygen may be useful to reduce fetal hypoxia.5 However, data supporting this are sparse. Therefore, we conducted a prospective, double-blinded, controlled study in which mothers were allocated randomly to breathe different inspired oxygen fractions (FIO2) during elective Caesarean section under spinal anaesthesia. We aimed specifically to determine the effect of FIO2 on umbilical cord blood gases and oxygen content in cases where the U–D interval was prolonged to greater than 180 s.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
This study received approval from the Clinical Research Ethics Committee of the Chinese University of Hong Kong. Non-labouring ASA I–II term parturients scheduled for elective Caesarean section under spinal anaesthesia were recruited after informed written consent. Patients were premedicated with ranitidine 150 mg orally the night before and on the morning of surgery. On arrival in the operating theatre, i.v. access was secured and standard monitoring, comprising non-invasive blood pressure cycled at 1 min, electrocardiogram and pulse oximetry, was attached. After an i.v. preload of 20 ml kg–1 of lactated Ringer’s solution, spinal anaesthesia was performed with the patient in the right lateral position. The patient was then turned supine with left lateral tilt, and prepared for surgery after checking that the level of the block was adequate.

Patients were allocated randomly, by drawing of shuffled opaque sealed envelopes, to breathe 21% (Group 21), 40% (Group 40) or 60% (Group 60) oxygen from the time of skin incision. Air or oxygen was supplied from a flowmeter to a masked high-flow Venturi-type facemask (Intersurgical, Wokingham, UK) to provide the assigned FIO2. Before each case, to maintain blinding of the investigators, an assistant connected the tubing from the flowmeters via an opaque relay box and confirmed the FIO2 using an oxygen analyser.

The times from starting oxygen supplementation to delivery, skin incision-to-delivery (I–D) interval and U–D interval were recorded using a stopwatch. A paediatrician who was unaware of group allocation attended each delivery and assessed Apgar scores.

Umbilical arterial (UA) and venous (UV) blood samples were collected into heparinized syringes from a segment of umbilical cord that was double-clamped before the infant’s first breath, and were analysed immediately. Blood gas analysis was performed using a Corning 278 pH/blood gas analyser (Medfield, MA, USA). Oxyhaemoglobin saturation and oxygen content were measured using an IL 682 Co-oximeter (Instrumentation Laboratory, Lexington, MA, USA) with correction for 70% fetal haemoglobin. The investigator performing all the blood analyses was blinded to patient allocation and did not participate in patient care. Results were recorded for analysis after completion of the study.

Identical management according to a set of predetermined protocols was provided by an anaesthetist who was blinded to the FIO2. Our contingency for patients who developed a pulse oximetry reading of <95% was to withdraw the patient from the study, and to administer the appropriate FIO2 to restore the oximetry reading to >=95%. Such cases were noted, but were excluded from analysis. Hypotension, defined as a decrease in systolic arterial pressure by >20% from baseline or to <100 mm Hg,6 was treated with i.v. boluses of ephedrine 9 mg as required. Nausea and vomiting were treated with metoclopramide 10 mg i.v. once hypotension had been excluded.

Statistical analysis
Using previously recorded data, we estimated the mean and standard deviation of UV oxygen content to be 13.1 and 2.2 ml dl–1 respectively. Prospective power analysis was performed to determine the number of cases with prolonged U–D interval that would be required. This showed that a sample size of 13 patients in each group would yield 80% power to detect a 2.6 ml dl–1 (20%) increase in oxygen content with a type I error probability of 0.05. This effect size of 2.6 ml dl–1 was proposed on the basis of Ramanathan’s report of an increase in oxygen content by 2.74 ml dl–1 when FIO2 was increased from 0.21 to 0.47.7 For the purposes of the study, the U–D interval was defined a priori as being prolonged when it was >180 s, which is the magnitude shown previously by Datta and Bader et al. 3 4 as being associated with fetal acidosis. Thus, patients were recruited into the study continuously until the study termination criterion of having at least 13 patients with a prolonged U–D interval in each group was reached. For analysis, patients were subdivided according to whether or not the U–D interval was prolonged.

Intergroup comparisons were made using analysis of variance (ANOVA) and the Kruskal–Wallis test with post hoc comparisons using the Tamhane and Bonferroni procedures. The {chi}2 test for trend was used to assess any dose–response relationship, and the association between the parameters (UV PO2 and UV oxyhaemoglobin saturation) were compared using multiple regression analysis and Pearson correlation. Results are presented as mean and standard deviation or median and range where appropriate. A value of P<0.05 was considered significant.


    Results
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
A total of 212 patients were recruited before we fulfilled the study termination criterion of having at least 13 patients in each oxygen group with a prolonged U–D interval. Complete data from 204 cases were used for analysis. Data from eight patients were excluded: six because insufficient umbilical blood was obtained, one who vomited and did not wear the facemask during uterine incision, and one who withdrew from the study after complaining of discomfort from wearing the facemask. The U–D interval ranged from 31 to 310 s, and overall 69 cases were recruited to Group 21, 62 cases to Group 40 and 73 cases to Group 60. Of these, 14 patients in Group 21, 18 patients in Group 40 and 13 patients in Group 60 had a prolonged U–D interval.

The indications for surgery are summarized in Table 1. Maternal characteristics, operative time intervals, incidence of hypotension and ephedrine consumption were similar among groups (Table 2). Maternal arterial oxyhaemoglobin saturation was maintained in all cases, with no case requiring a change in the assigned FIO2. Neonatal oxygen data and outcome are summarized in Tables 3 and 4.


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Table 1 Indications for surgery. Values are number (%)
 

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Table 2 Maternal characteristics, operative intervals, incidence of hypotension and ephedrine consumption. Values are mean (range) for age, mean (SD) or median [range]
 

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Table 3 Neonatal oxygenation data for patients with or without a prolonged uterine incision-to-delivery (U–D) interval of 180 s. Values are mean (SD). *Significantly different from Groups 21 and 40 (P<0.05)
 

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Table 4 Neonatal outcome data for patients with or without a prolonged uterine incision-to-delivery (U–D) interval of 180s. Values are mean (SD), median [range] or number (%)
 
Patients without prolonged U–D interval
The UV PO2 was significantly different among groups and was greater in Group 60 than in Group 21 (4.3 (1.1) vs 3.7 (1.0) kPa; mean difference 0.56 kPa, 95% CI of difference 0.19–0.90 kPa, P=0.003). Similarly, the UV oxygen content was significantly different among groups and was greater in Group 60 than in Group 21 (14.4 (3.3) vs 12.9 (2.7) ml dl–1; mean difference 1.36 ml dl–1, 95% CI of difference 0.4–2.6 ml dl–1, P=0.007). No increase in UV PO2 or oxygen content was observed in Group 40 compared with Group 21, and other blood gas measurements were similar among the groups. One baby in Group 60 had an Apgar score of 6 at 1 min. All other Apgar scores at 1 min and 5 min were >=7.

Patients with prolonged U–D interval
The UV PO2 was significantly different among groups and was greater in Group 60 than in Group 21 (4.6 (0.6) vs 3.9 (0.8) kPa; mean difference 0.7 kPa, 95% CI of difference 0.13–1.30 kPa, P=0.019). The UV oxygen content and other blood gas measurements were similar among groups. No Apgar score was <7 at 1 or 5 min.

Combined patients
There was no difference in blood gas measurements, oxygen content or Apgar scores between cases with and without prolonged U–D interval. The incidence of fetal acidosis, defined as UA pH <7.2, was similar between cases with and without a prolonged U–D interval (4/45 (8.9%) vs 11/159 (6.9%), P=0.90). The overall incidence of fetal acidosis was evenly distributed among groups (Group 21, 7.2%; Group 40, 9.6%; Group 60, 6.9%; P=0.92) and there was no relationship between the severity of acidosis and the magnitude of the U–D interval (r=–0.098, P=0.165). Using multiple regression analysis to adjust for the FIO2, there was no association between prolonged U–D interval and UV PO2 (P=0.103), UA pH (P=0.17) or Apgar scores (P=1.0). A correlation was found between UV PO2 and UV oxygen content (r=0.7, P=0.0004). A plot of UV PO2 against UV oxyhaemoglobin saturation (Fig. 1) confirmed the presence of a sigmoid relationship, with the curve described by the equation:



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Fig 1 Sigmoid plot of umbilical venous oxygen partial pressure vs oxyhaemoglobin saturation (r2=0.27).

 
Saturation=100/[1+100.4(3–Po2)]


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Our study showed that, within the range of values observed, a U–D interval of >180 s was not associated with worse neonatal acid–base status, oxygenation or Apgar scores compared with a U–D interval <180 s. In patients without a prolonged U–D interval, administration of 60% oxygen, but not 40% oxygen, increased the oxygen content of UV blood, but the mean magnitude of the increase (11.6%) was modest compared with patients who breathed air. For patients with a prolonged U–D interval, administration of oxygen did not increase the UV oxygen content. Together, these data do not support the routine administration of supplementary oxygen during spinal anaesthesia for elective Caesarean section for the purpose of improving the fetal oxygen reserve or well-being during a prolonged U–D interval.

Our results contradict the findings of some previous studies. Datta and colleagues4 reported that a U–D interval >180 s was associated with worsening neonatal acid–base status and low Apgar scores in patients who had spinal anaesthesia. Bader and colleagues3 reported that a prolonged U–D interval was correlated with a greater incidence of low Apgar scores and worsening neonatal acid–base values in patients who had spinal and epidural anaesthesia. It was suggested that the fetal hypoxia and acidosis were the result of compromised placental circulation caused by prolonged U–D intervals.4 5 Because of this, it has been suggested that administration of supplementary oxygen might improve fetal oxygenation when the U–D interval is prolonged.5 Our results, however, suggest that this is unlikely.

The reasons why our results differ from the previous reports are unclear. It is possible that some aspects of anaesthetic technique or operative practice have improved since the previous publications. For example, hypotension is treated more rapidly, and advances in imaging techniques have resulted in better awareness of the position and orientation of the feto-placental unit to facilitate a smooth delivery. The range of U–D intervals in our study was 31–310 s and may have differed from the range of prolonged U–D intervals which were not reported in the previous studies. Unlike our study, in the reports by Datta and Bader, patients who developed hypotension were specifically excluded. However, because hypotension occurs in most cases of spinal anaesthesia in obstetrics,8 it can be argued that the previous papers were not truly representative of the usual clinical situation. In previous work, we analysed the factors associated with fetal acidosis during spinal anaesthesia for Caesarean section.9 We found that although a prolonged U–D interval was a significant predictor of fetal acidosis, its magnitude of association was small compared with other factors, such as hypotension and the use of ephedrine.

Because of the unpredictable nature of U–D intervals, our study faced several design obstacles. In particular, it would be necessary to recruit a very large number of patients to include the required numbers with a prolonged U–D interval in each group. Our approach in this study—to identify patients with prolonged U–D intervals retrospectively after each case—was more efficient, although it is theoretically possible that such patients may differ from other patients in some other unknown confounding variable. We were, however, unable to detect such a variable in our multiple regression analysis.

In our previous study, we found that administering 60% oxygen during elective Caesarean section under spinal anaesthesia increased the UV PO2 by 20% compared with air.2 However, in that study we did not measure oxygen content. Similarly, most other studies have relied solely on the PO2 or derived values of oxygen content as comparators. In contrast, in the present study we used co-oximetry as a more direct measure of oxygen content. Previously, Ramanathan et al.7 estimated UV oxyhaemoglobin saturation from measured UV PO2 and suggested that there was an almost linear increase of oxygen content with increasing FIO2. They estimated that oxygen content increased by 2.74 ml dl–1 when FIO2 was increased from 0.21 to 0.47. In comparison, our results using co-oximetry showed that increasing FIO2 from 0.21 to 0.60 resulted in a smaller increase in oxygen content, of 1.36 ml dl–1. The plot of UV PO2 against UV oxyhaemoglobin saturation from our study (Fig. 1) confirmed a sigmoid relationship, with a value for P50 of 3.0 kPa, which is similar to the published reference mean (SD) value of 2.87 (0.21) kPa.10 Although the nature of the curve is influenced by our assumption that the proportion of fetal haemoglobin was 70%, it is based on directly measured variables and takes into account the dynamic effects of factors such as acids, carbon dioxide, adenosine triphosphate and 2,3-diphosphoglycerate. Thus, our plot represents an in vivo estimate of the relationship between oxyhaemoglobin saturation and PO2. This may explain the difference in our results compared with those of Ramanathan et al., as their calculated values may not have taken into account all of these factors.

Finally, in our study we found there was no increase in the UV PO2 or oxygen content when 40% oxygen was administered compared with air. This is consistent with studies by Kelly and colleagues,11 who administered 35% oxygen, and Cogliano and colleagues,12 who administered 40% oxygen, and also found no increase in UV PO2. This may be a reflection of the functional shunting of the placental circulation, which means that a much greater maternal FIO2 is required to increase UV blood oxygenation.13

In summary, our findings did not show any benefit of routine administration of supplementary oxygen during elective Caesarean section for cases in which the U–D intervals were prolonged.


    Acknowledgements
 
We wish to thank the staff of the Labour Ward, Prince of Wales Hospital, Shatin, Hong Kong SAR, China for their cooperation, and Ms Perpetua Tan and Mr Bryan Ng, Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, for technical help.


    References
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 Backe SK, Lyons G. Oxygen and elective Caesarean section. Br J Anaesth 2002; 88: 4–5[Free Full Text]

2 Khaw KS, Wang CC, Ngan Kee WD, Pang CP, Rogers MS. Effects of high inspired oxygen fraction during elective Caesarean section under spinal anaesthesia on maternal and fetal oxygenation and lipid peroxidation. Br J Anaesth 2002; 88: 18–23[Abstract/Free Full Text]

3 Bader AM, Datta S, Arthur GR, Benvenuti E, Courtney M, Hauch M. Maternal and fetal catecholamines and uterine incision-to-delivery interval during elective cesarean. Obstet Gynecol 1990; 75: 600–3[Abstract]

4 Datta S, Ostheimer GW, Weiss JB, Brown WU Jr, Alper MH. Neonatal effect of prolonged anesthetic induction for cesarean section. Obstet Gynecol 1981; 58: 331–5[Abstract]

5 Jordan MJ. Women undergoing caesarean section under regional anesthesia should routinely receive supplementary oxygen. Int J Obstet Anesth 2002; 11: 282–5.[CrossRef][ISI]

6 Rout CC, Akoojee SS, Rocke DA, Gouws E. Rapid administration of crystalloid preload does not decrease the incidence of hypotension after spinal anaesthesia for elective Caesarean section. Br J Anaesth 1992; 68: 394–7[Abstract]

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9 Ngan Kee WD, Lee A. Multivariate analysis of factors associated with umbilical arterial pH and standard base excess after Caesarean section under spinal anaesthesia. Anaesthesia 2003; 58: 125–30[CrossRef][ISI][Medline]

10 Lentner C. Heart and circulation: blood gases. In: Lentner C, ed. Geigy Scientific Tables. West Caldwell, New Jersey: Ciba-Geigy, 2003; 198–200

11 Kelly MC, Fitzpatrick KT, Hill DA. Respiratory effects of spinal anaesthesia for caesarean section. Anaesthesia 1996; 51: 1120–2[ISI][Medline]

12 Cogliano MS, Graham AC, Clark VA. Supplementary oxygen administration for elective Caesarean section under spinal anaesthesia. Anaesthesia 2002; 57: 66–9[ISI][Medline]

13 Bassell GM, Marx GF. Optimization of fetal oxygenation. Int J Obstet Anesth 1995; 11: 238–43[CrossRef]