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Effect of Different Inspired Oxygen Concentrations During Caesarean Section Under Spinal Anaesthesia on Maternal and Foetal Oxygenation and Lipid Peroxidation
Veena Singh*, Sarla Hooda+, Kiran Dahiya**, Rajesh Sharma#

 

Abstract
This study was planned to evaluate the effects of different inspired oxygen concentrations in 60 non-labouring patients scheduled for elective caesarean section divided in 3 groups (21% i.e. atmospheric air for group I, 35% for group II and 60% for group III) on blood gas analysis and lipid peroxidation markers before and at the time of delivery for mothers and in umbilical vein and artery for foetuses. It was found that the increase in inhaled oxygen concentration is associated with an increase in maternal and foetal PO2, plasma malondialdehyde and 8-isoprostane (p < 0.01). In foetuses, significant rise in malondialdehyde and uric acid levels was seen with 60% of inhaled oxygen concentration only. Thus breathing high inspired oxygen concentration by the mother increases maternal and foetal oxygenation but also causes concomitant increase in oxygen free radical activity in both mother and foetus which may have consequences in their later life.

Introduction

Spinal anaesthesia is a popular technique for elective caesarean section. An intraoperative deterioration in pulmonary function tests occur as a result of the motor block which accompanies the sensory block in spinal anaesthesia.1 To prevent maternal oxyhaemoglobin desaturation and optimize foetal arterial oxygenation, prophylactic supplemental oxygen inhalation is administered to the mother.

It has been observed that on increasing the concentration of maternal inhaled oxygen, there is an increase in maternal and foetal oxygen partial pressure (PO2) and an improvement in the umbilical blood gas and acid base parameters.2,3 It has also been seen that breathing high FiO2 (fractional inspired oxygen concentration) is associated with concomitant increase in oxygen free radical activity in mother and foetus.4 When these free radicals attack cell membrane lipids, organic hydroperoxides are formed, which then generate malondialdehyde, MDA.5 So this study was conducted to find out the effects of different inspired oxygen concentrations i.e. 21% (air group), 35% and 60% on maternal and foetal oxygenation and free radical formation. Their effect on foetal outcome following elective caesarean was also assessed.

Material and Methods

This study was conducted on 60 pregnant females having uneventful antenatal period, scheduled for elective caesarean section under spinal anaesthesia. Prior informed consent was obtained from the subjects and approval by local ethical committee was approval by local ethical committee was obtained before starting this work. These patients were kept fasting 6 hours prior to the scheduled time of surgery and received no premedication. Continuous monitoring for non-invasive blood pressure (NIBP), heart rate, electrocardiogram and arterial oxygen saturation (SpO2) was set up. Intravenous preloading was done with 15 ml/Kg lactated Ringer’s solution. Baseline reading of maternal pulse, NIBP and SpO2 sat were recorded and patients divided randomly into three groups:

Group I (n=20): After administration of spinal anaesthesia, these patients continued to breathe atmospheric air throughout the procedure without any oxygen supplementation.

Group II (n=20): These patients received 35% oxygen in air using a ventimask throughout the procedure.

Group III (n=20): These patients received 60 % oxygen using a ventimask throughout the surgery.

Randomization was done by draw of chits labeled as 21% oxygen, 35% oxygen or 60% oxygen. Spinal anaesthesia was administered in right lateral position using 2 ml of 0.5% hyperbaric bupivacaine injected intrathecally at L3-L4 space in each patient. The patients were turned supine with left lateral tilt and after collecting baseline maternal arterial sample, were started inhalation of assigned FiO2. The number of episodes of hypotension, bradycardia and desaturation, if any, were noted down and total dose of mephentermine and atropine administered to rectify these episodes was also recorded.
The time from anaesthesia to delivery (A-D), skin incision to delivery (I-D) and uterine incision to delivery (U-D) were recorded. Apgar scores of the newborn at 1 and 5 minutes, birth weight and maturity in weeks were also recorded.

A maternal arterial and fetal umbilical arterial (UA) and venous (UV) heparinised blood samples were collected at the time of delivery. Blood gas analysis (BGA) was performed immediately for each sample. The remaining sample was centrifuged and the plasma analyzed for 8-isoprostaglandin F2a(8-isoprostane), malondialdehyde (MDA) and uric acid.

8-isoprostane levels were estimated by ELISA,6 MDA levels colorimetrically using thiobarbituric acid7 and uric acid levels colorimetrically using phosphotungstic acid8.

Statistical analysis: The results were statistically analyzed using one way ANOVA test, student’s ‘t’ test, Chi-square test and paired ‘t’ test.

Results

All the sixty patients included in the study belonged to American society of anaesthesiologists status I. I-D time, U-D time, A-D time in all the three groups was comparable (ANOVA, p=0.464, 0.986, 0.499 respectively). All the three groups delivered full term (38 ± 2 weeks) babies with birth-weights being 2.80 ± 0.31Kg, 2.75 ± 0.17 Kg and 2.91 ± 0.24 Kg in each group respectively (One way ANOVA p= 0.142). The difference in Apgar scores at 1 minute and 5 minutes in all the three groups was statistically insignificant (p= 0.763, 0.533 for 1 minute and 5 minutes respectively). Six patients in group I, Seven patients in group II and Five patients in group III had intra-operative 7, 9 and 6 episodes of hypotension respectively which are found to be comparable using Chi-square tests. Dose of mephentermine required to treat these episodes is also comparable in the three groups (p=0.567). Two patients in each group had bradycardia and each episode responded to 0.3 mg of atropine.

Results of maternal blood gas analysis, baseline and at delivery are represented in Table 1. Baseline blood gas parameters are statistically comparable in all the three groups. Maternal arterial PO2 at the time of delivery is higher in group II and group III as compared to group I. Other parameters are comparable statistically. In group I and III, maternal PCO2 at delivery is significantly lower than the baseline value (p=0.001, p=0.005). In group II, III, maternal PO2 is significantly greater at delivery than at the baseline. Results of fetal blood gas analysis in umbilical artery and vein are shown in Table 2. Umbilical artery PO2 (UAPO2) is significantly higher in group III as compared to group II and the values are higher in groups II and III as compared to group I. Other parameters are comparable. Umbilical vein PO2 (UVPO2) is significantly lower in groups II and I as compared to group III and

groups II and I as compared to group III and value in group II is higher than group I. Maternal lipid peroxides (Table 3) are comparable in all three groups in baseline samples. At delivery, 8-isoprostane levels are significantly higher in group III as compared to group II and group I. The levels in group II are significantly high as compared to group I. MDA levels are significantly high in group III as compared to group I but the difference is not significant when compared with group II. In group I, baseline MDA and 8-isoprostane levels are not significantly high as compared to baseline levels while levels have increased significantly in group II and III. Uric acid levels are comparable in all the three groups while the levels at delivery are significantly higher than those at baseline in groups II and III. Foetal lipid peroxidation products are shown in Table 4. UA and UV 8-isoprostane levels have increased significantly with increase in oxygen concentration. MDA levels in both UA and UV samples were found to be increased significantly in group III as compared to group I. These levels are more in umbilical vein as compared to umbilical artery. Uric acid levels in group III are significantly greater than group I in both

significantly greater than group I in both umbilical arterial and venous samples.

Discussion

In our study, we have observed that when mothers were given 35% or 60% oxygen, their arterial PO2 increased with linear increase in umbilical blood PO2. Maternal blood pH and base excess were found to be comparable in the three groups as has been reported by other authors also.3,4,9 It was also observed that 8-isoprostane levels in maternal blood increased with increase in concentration of inhaled oxygen and maternal MDA levels at delivery were found to be raised in group II and III which is in accordance with other studies.3,10 Maternal uric acid levels were found to be similar in all the three groups suggesting an absence of ischaemia – reperfusion mediated free radical formation in mother. Umbilical blood 8-isoprostanes were found to be increased with increase in maternal inspired oxygen concentration. Foetal MDA also increased significantly with increase in oxygen concentration but uric acid levels were not found to be significantly different between umbilical arterial and venous samples. Their levels increased significantly in group III only.

Campbell et al, 1966, observed that a rise in PO2 of the blood perfusing the placenta resulted in vasoconstriction.11 8-Isoprostanes have also been found to be vasoconstrictors.12 Hence, these can be possible reasons for some ischemia- reperfusion injury exacerbated by hyperoxia leading on to increase in fetal uric acid levels in 60% oxygen group. It was also found that lipid peroxide concentrations were much greater in UV than in UA suggesting that the main site of free radical activity is the placenta. This finding signified a direct relationship between PO2 and the extent of free radical activity in foeto-placental unit. The concentration of 8-isoprostanes was greater in umbilical vessels than in maternal blood implying that their generation is at the foeto-placental unit as was implicated by Khaw et al.4

Neonatal outcome is comparably favourable in all the three groups and this can be attributed to comparable U-D time, performance of left lateral tilt and also early use of vasopressors and atropine to treat hypotension and bradycardia. Various other studies have also concluded that foetal outcome is not affected by increasing the concentration of inhaled oxygen.1,4,13

Therefore, we conclude that although inhaling high oxygen concentration by the mother increased the maternal and foetal oxygenation but also caused the concomitant increase in the free radical activity in both mother and fetus without having an adverse effect on foetal outcome. So this oxygen supplementation is not beneficial only but may prove to be harmful in later life.

References

  1. Kelly MC, Fitzpatrick KT, Hill DA. Respiratory effects of spinal anaesthesia for caesarean section. Anaesthesia 1996; 51 : 1120-2.
  2. Baraka A. Correlation between maternal and fetal PO2 and PCO2 during caesarean section. Br J Anaesth 1970; 42 : 434-8.
  3. Marx GF, Mateo CV. Effects of different oxygen concentrations during general anesthesia for elective caesarean section. Can Anaesth Soc J 1971; 18: 587-93.
  4. Khaw KS, Wang CC, Ngan Kee WD, et al. The 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.
  5. Halliwell B, Gutteridge JM. Lipid peroxidation, oxygen radicals, cell damage and antioxidant therapy. Lancet 1984; 1 : 1396-7.
  6. Engler MB, Engler MM. Flavinoid – rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J Am Coll Nutr 2004; 23 : 197-204
  7. Buege JA, Aust SD. The thiobarbituric acid assay. Meth Enzymol 1978; 52 : 306-7.
  8. Newman DJ, Price CP. Renal function and nitrogen metabolites. In: Burtis CA, Ashwood ER editors. Tietz textbook of clinical chemistry, 3rd edition. Philadelphia: WB Saunders 1999; 1249.
  9. Ramanathan S, Gandhi S, Arismendy J, et al. Oxygen transfer from mother to fetus during caesarean section under epidural anesthesia. Anesth Analg 1982; 61 : 576-81.
  10. Rogers MS, Mongelli M, Tsang KH, et al. Fetal and maternal levels of lipid peroxides in term pregnancies. Acta Obstet Gynecol Scand 1999; 78 : 120-4.
  11. Campbell AM, Dawes GS, Fishman AP, et al. The oxygen consumption of the placenta and fetal membranes in the sheep. J Physiol 1966; 182 : 439-64.
  12. Morrow JD, Hill KE, Burk RF, et al. A series of prostaglandin F2 like compounds are produced in vivo in humans by non- cyclooxygenase, free radical catalyzed mechanism. Proc Natl Acad Sci USA 1990; 87 : 9383-7.
  13. Fox GS, Smith JB, Namba Y, et al. Anesthesia for caesarean section: Further studies. Am J Obstet Gynecol 1979; 133 : 15-9
 
*Professor and Head, **Lecturer, Department of Biochemistry; +Professor and Head, Department of Anaesthesia; #Ex-resident; Pt. B.D. Sharma PGIMS, Rohtak, Haryana, India.
 
TREATING TO NEW TARGETS STUDY

The study thus provides evidence to suggest that patients with coronary heart disease and metabolic syndrome are good candidates for intensive lipid-lowering therapy’

The metabolic syndrome-the clustering of cardiovascular risk factors including insulin resistance, obesity, hypertension, and dyslipidaemia - has been closely linked to the development of diabetes and cardiovascular disease. Despite the prognostic value of metabolic syndrome for predicting cardiovascular events, few trials have investigated the effects of statin therapy on cardiovascular morbidity and mortality in patients with the syndrome. Prakash Deedwania and colleagues did a post hoc analysis of the Treating to New Targets (TNT) study to assess whether intensive lowering of low-density lipoprotein cholesterol with high-dose atorvastatin therapy results in cardiovascular benefits for patients with both coronary heart disease and the metabolic syndrome. The investigators noted that such patients derive incremental benefit from high-dose atorvastatin therapy, irrespective of the presence of diabetes. In a Comment, Andre Scheen states that the presence of metabolic syndrome might help select patients who will benefit the most from aggressive lipid-lowering therapy.

Lancet, 2006; 893, 919.

 
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