Analysis of Neonatal Outcome with Supplemental Oxygen to Mother during Elective Cesarean Section under Spinal Anesthesia: A Prospective Randomized Controlled Trial.

BACKGROUND: Many questions have arisen on benefits of routine use of supplemental oxygen during elective cesarean section (CS) under spinal anesthesia. AIMS: The aim of this randomized controlled study was to evaluate neonatal outcome in immediate postpartum period with or without supplemental oxygen to mother, undergoing elective CS under spinal anesthesia.
MATERIALS AND METHODS: One hundred and thirty-four nonlaboring term pregnant women were allocated randomly into two groups to breathe room air (air group) or oxygen (oxygen group). Times from starting oxygen supplementation to delivery interval, skin incision to delivery (I-D) interval, and uterine incision to delivery (U-D) interval were recorded. APGAR scores were assessed at 1 min and 5 min after delivery. Umbilical cord blood gas analysis was done immediately to measure pH, oxygen partial pressure, carbon dioxide partial pressure (PCO2), and bicarbonate. STATISTICAL ANALYSIS: Statistical comparisons were performed using either Student's t-test or Mann-Whitney U-test.
RESULTS: For oxygen group versus air group, In Oxygen group, proportion of fetal acidosis was significantly less; umbilical arterial (UA) blood pH (7.22 ± 0.05 vs. 7.19 ± 0.05, P = 0.001) as well as umbilical venous (UV) blood pH (7.26 ± 0.05 vs. 7.22 ± 0.06, P < 0.001) were significantly higher and UA PCO2 (55.4 ± 9.9 vs. 62.9 ± 6.9, P = 0.001) and UV PCO2 (51.4 ± 8.2 vs. 54.3 ± 7.2, P = 0.036) were significantly lower compared to air group. APGAR scores were similar between the groups.
CONCLUSIONS: Supplemental oxygen has potential benefits as demonstrated by less proportion of FA in mothers receiving supplemental oxygen. Copyright:

INTRODUCTION

Administration of supplemental oxygen to mother during cesarean section (CS) under spinal anesthesia has been a routine practice for >30 years.[12] Spinal anesthesia is usually associated with a decrease in blood pressure which may cause tissue hypoxia, affecting both mother and fetus adversely during CS.[34] Using conventional monitors (e.g., noninvasive blood pressure and pulse oximetry), there is a time lag between the occurrence of hypotension (and thus hypoxia), its detection, and institution of effective therapy. Thus, these patients will invariably be exposed to a period of hypoxia that can have adverse effect on the fetus.[5] Well-established methods to prevent and treat this hypotension are volume expansion, use of vasopressors, and appropriate patient positioning.[46] Supplemental oxygen is also administered to mother during spinal anesthesia in obstetric practice as a part of prevention and management of tissue hypoxia secondary to postspinal hypotension.[6] Besides, for performance of CS, sensory block should cover at least sixth thoracic (T6) dermatome and this may lead to deterioration in respiratory mechanics. When patients are placed supine following spinal anesthesia, significant reduction in peak expiratory flow, forced vital capacity, forced expiratory volume in 1 s, and forced expiratory flow in the mid region of the forced vital capacity usually occur.[5] Any of these conditions may also cause fetal academia.[47] Administering supplemental oxygen will not prevent the problem but may help to improve oxygen delivery[8] and thus may benefit the fetus during this critical time,[4] especially when baby delivery is prolonged due to increased uterine incision to delivery time which has been associated with fetal acidosis (FA).[89] However, oxygenation has its own side effects related to maternal hyperoxia and concomitant increase in oxygen-free radical activity in both mother and fetus, especially in high inspired concentration.[1011] Hence, the benefit of administering supplemental oxygen routinely during elective cesarean delivery under regional anesthesia to improve neonatal outcome in immediate postpartum period is controversial,[1213] and many questions on benefits of routinely administering supplemental oxygen have arisen. Since there is no clear guideline about this and supporting data are sparse, we have conducted a randomized controlled study with an objective to contribute for a suggested guideline by determining whether low-dose supplemental oxygen support to mother is helpful to prevent FA, improving neonatal outcome in the immediate postpartum period during elective CS under spinal anesthesia.

MATERIALS AND METHODS

After taking approval from the institutional ethics committee and registering at Clinical Trial Registry India (www.ctri.nic.in: CTRI/2013/08/003894), this study was conducted from August 2013 to September 2014. A total of 134 nonlaboring American Society of Anesthesiologists Physical Status Classes I and II term pregnant women, scheduled for elective CS under subarachnoid block, were recruited after taking proper written informed consent and were divided into two groups with 67 participants in each group. Patients were allocated randomly, by drawing of shuffled opaque-sealed envelopes, to breathe room air (air group) or oxygen at 3 L/min via nasal cannula (oxygen group). Nasal cannula, a low flow oxygen delivery system, was used in our study as nasal cannula is better tolerated than facemasks by patients and remains in situ in case of vomiting. Participants with any sort of suspected fetal anomaly, any medical complication of mother which may interfere with fetoplacental perfusion, skin incision to baby delivery time (I-D) >30 min, and/or uterine incision to baby delivery time (U-D) >5 min were excluded from this study.

Patients received ranitidine 150 mg orally, the night before and on the morning of surgery. Anesthesia machine, airway equipment, drugs for resuscitation, and general anesthesia were kept ready in hand before starting the procedure. Monitoring included continuous electrocardiography (ECG), pulse rate, oxygen saturation (SPO2), noninvasive blood pressure, and respiratory rate.

Before performing subarachnoid block, an intravenous (IV) line was established with an 18G IV cannula in a large vein and IV fluid was started with Ringer's lactate solution. Monitoring included noninvasive arterial pressure, ECG, and pulse oximetry. Just before performing spinal anesthesia, a nasal cannula was applied to the oxygen group and participants then received either oxygen 3 L/min via a nasal cannula (oxygen group) or air (air group) as allocated after randomization. After administering a preload with 10–15 mL/kg of lactated Ringer's solution, a 26G Quincke spinal needle was introduced into L3–L4 intervertebral space by midline approach under strict aseptic precautions with the patient in the right lateral position, and after confirming free flow of cerebrospinal fluid in all four quadrants, 10 mg of 0.5% hyperbaric bupivacaine was administered at the rate of approximately 0.2 mL/s without barbotage. The patient was then turned supine with 15° left lateral tilt and prepared for surgery after checking that the level of block was adequate (tested by cold sensation or pinprick). Surgeons were allowed to proceed only when sensory block reached at least the level of T6 dermatome or above. Blood pressure was measured at every 1 min after spinal injection until delivery and every 3 min until the end of the procedure. Hypotension was managed immediately on detection, by injection phelylephrine 50–100 mg IV bolus (titrated to patient response) along with fluids (both crystalloids and colloids). Bradycardia was managed by injection atropine 0.5 mg IV bolus. A reduction of SpO2 <94% for >30 s was considered as desaturation, confirmed by good signal quality and no probe displacement.[1415] This is a modification from the recommendation from O’Driscoll et al.[14] and Van de Louw et al.[15] When desaturation was detected, the participants were treated with supplemental oxygen immediately to keep SpO2 >94%.

The time from starting oxygen supplementation to delivery, I-D interval, and U-D interval were recorded using a stopwatch. A pediatrician who was unaware of group allocation attended each delivery and assessed APGAR scores at 1 min and 5 min after baby delivery. Umbilical arterial (UA) and umbilical 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 blood gas analysis was done immediately to measure oxygen partial pressure (PO2), carbon dioxide partial pressure (PCO2), SpO2, pH (pH <7.2 was considered as FA), and bicarbonate. Investigator performing all blood analyses was blinded.

Statistical analysis

From previous study, we found the mean and standard deviation (SD) of UA PO2 to be 14.25 and 4.5 mmHg (14.25 ± 4.5), respectively, and prospective power analysis showed that a sample size of 134 (67 in air group and 67 patients in oxygen group) would yield 85% power to detect a 2.25 mmHg (15%) increase in UA PO2 with a Type I error probability of 0.05. Data were tested for equality of variance using Levene's test and Kolmogorov–Smirnov test was used to test the normality assumption. On the basis of findings, statistical comparisons were performed using either Student's t-test or Mann–Whitney U-test. Chi-square test was used for comparison of equality of proportion. The statistical software used were PASW® (Predictive Analytics Software), SPSS Statistics for Windows 7® version 18.0.0 (Chicago:SPSS Inc.) and GraphPad Prism® Instat version 5.0. (California:GraphPad Software Inc.). Microsoft® Office Excel 2010 (Washington:Microsoft) was used to draw the scatter diagrams and trend line for the two groups. Results are presented as mean ± SD, median (range), or percentage where appropriate. P < 0.05 was considered statistically significant.

RESULTS

Sixty-seven patients in each group were initially taken up for the study. Of these, 66 patients in air group and 61 patients in oxygen group could complete the study [Figure 1].

Figure 1

Consort flow diagram

Maternal data

Maternal age and parity characteristics, I-D interval, U-D interval, and duration of maternal oxygen exposure (from air or via nasal cannula) to delivery interval were similar between the air and oxygen groups [Table 1].

Table 1

Maternal characteristic details

	Air group (n=66)	Oxygen group (n=61)	P
Age (years)	26.3±4.6	25.8±3.9	0.51
Parity (median with range)	0 (0-4)	0 (0-2)	0.45
I-D interval (min)	6.1±2.6	5.8±2.7	0.53
U-D interval (s)	125±71.5	113±66.7	0.33
Maternal oxygen exposure (from air or via nasal cannula)-to-delivery interval (min)	12.8±4.2	13.5±4.2	0.35

Values are represented as mean±SD or median (range). SD=Standard deviation, I-D=Skin incision-to-delivery, U-D=Uterine incision-to-delivery

Neonatal umbilical artery and umbilical vein blood gas analysis and neonatal outcome (in immediate postpartum period) [Tables 2 and 3]

In the oxygen group compared to the air group, In Oxygen group, proportion of fetal acidosis was significantly less; umbilical arterial (UA) blood pH (7.22 ± 0.05 vs. 7.19 ± 0.05, P = 0.001) as well as umbilical venous (UV) blood pH (7.26 ± 0.05 vs. 7.22 ± 0.06, P < 0.001) were significantly higher and UA PCO2 (55.4 ± 9.9 vs. 62.9 ± 6.9, P = 0.001) and UV PCO2 (51.4 ± 8.2 vs. 54.3 ± 7.2, P = 0.036) were significantly lower compared to air group. Hence, we observed higher pH values along with lower PCO2 in both UA and UV blood in subjects who received oxygen, and proportion of FA was also significantly less in subjects who received oxygen compared to air group. There was no difference between the groups in UA or UV PO2. UA bicarbonate levels were higher for the air group compared to the oxygen group (23.1 ± 2.5 vs. 22.1 ± 2.0, P = 0.015) to compensate for a higher UA PCO2 in the air group. UV PCO2 levels were also significantly higher in the air group [Table 2]. Birth weight was similar between the groups. There were no statistically significant differences in APGAR scores [Table 3].

Table 2

Neonatal umbilical artery and umbilical vein blood gas analysis

	Air group	Oxygen group	P	95% CI of the difference
				Lower	Upper
UA blood gas analysis data
UA pH	7.19±0.05	7.22±0.05	0.001*	−0.001	0.026
FA (UA pH <7.20) (%)	39 (59)	22 (36)	0.016*
UA PO2 (mmHg)	14.6±6.7	15.2±6.2	0.60	−8.0567	−3.812
UA PCO2 (mmHg)	62.9±6.9	55.4±9.9	0.001*	1.938	1.209
UA bicarbonate (UV blood gas analysis data mol/L)	23.1±2.5	22.1±2.0	0.015*	−0.613	0.525
UV blood gas analysis data
UV pH	7.22±0.06	7.26±0.05	<0.001*	0.021	0.049
UV PO2 (mmHg)	21.0±7.9	21.4±6.4	0.75	−1.604	2.024
UV PCO2 (mmHg)	54.3±7.2	51.4±8.2	0.036*	−4.843	−0.808
UV bicarbonate (mmol/L)	22.4±2.1	21.9±1.9	0.16	−0.605	0.261

Values are mean±SD, median (range), or percentage format. *P values are statistically significant. UA=Umbilical artery, UV=Umbilical vein, PO2=Oxygen partial pressure, PCO2=Carbon dioxide partial pressure, FA=Fetal acidosis, CI=Confidence interval, SD=Standard deviation

Table 3

Neonatal outcome (in immediate postpartum period) data

Neonatal outcome data	Air group	Oxygen group	P
Birth weight (kg)	2.49±0.29	2.58±0.37	0.13
APGAR score (1 min)	8 (7-8)	8 (5-8)	0.29
APGAR score (5 min)	8 (7-9)	8 (6-8)	0.13
APGAR score (1 min) <7 (%)	0	2 (3.2)	0.46
APGAR score (5 min) <7 (%)	0	1 (1.6)	0.99

Values are mean±SD, median (range), or percentage format. SD=Standard deviation

Since proportion of FA was significant, further subgroups were done in both groups according to the presence or absence of FA (UA pH < 7.2). Then, blood gas analysis for the oxygen group versus the air group yielded statistically significant lower values of UA PCO2 in oxygen group than that for the air group for both FA (59.7 ± 6.3 [oxygen] vs. 68.8 ± 10.9 [air], P = 0.021) and no FA (NFA) subgroups (51.8 ± 6.2[oxygen] vs. 57.1 ± 7.9[air], P = 0.036) [Table 4]. UA pH was still significantly high in oxygen group in the FA subgroup (7.19 ± 0.04 [oxygen] vs. 7.16 ± 0.02[air], P = 0.026). There was no difference in UA or UV PO2 or bicarbonate levels. Birth weight and APGAR scores were similar between the subgroups FA and NFA. UA bicarbonate levels were higher for the air group than that for the oxygen group (23.1 ± 2.5 vs. 22.1 ± 2.0, P = 0.015) to compensate for a higher PCO2 in the air group. UV blood gas analysis data were similar between subgroups FA and NFA. Birth weight and APGAR scores were also similar between the subgroups FA and NFA.

Table 4

Umbilical artery and umbilical vein blood gas analysis data and neonatal outcome data for no fetal acidosis and fetal acidosis subgroups

	NFA			FA
	Air group (n=27)	Oxygen group (n=39)	P	Air group (n=39)	Oxygen group (n=22)	P
UA blood gas analysis data
UA pH	7.24±0.03	7.25±0.03	0.19	7.15±0.04	7.17±0.02	0.032*
UA PO2 (mmHg)	14.9±3.4	15.4±6.2	0.70	14.0±8.3	15.1±5.6	0.58
UA PCO2 (mmHg)	57.1±7.9	51.8±6.2	0.003*	68.8±10.9	59.7±6.3	0.001*
UA bicarbonate (mmol/L)	24.0±2.7	22.5±1.9	0.008*	22.5±2.3	21.3±2.1	0.048*
UV blood gas analysis data
UV pH	7.25±0.06	7.26±0.04	0.42	7.21±0.05	7.22±0.06	0.49
UV PO2 (mmHg)	21.5±4.0	22.6±6.5	0.44	19.5±9.8	19.9±6.4	0.86
UV PCO2 (mmHg)	53.7±8.1	51.0±6.9	0.15	54.7±6.8	51.7±9.8	0.17
UV bicarbonate (mmol/L)	22.9±2.7	22.4±1.9	0.38	22.3±1.3	21.6±1.5	0.061
Neonatal outcome data
Birth weight (kg)	2.55±0.23	2.61±0.25	0.32	2.43±0.34	2.54±0.48	0.30
APGAR score (1 min)	8 (7-8)	8 (6-8)	0.86	7 (7-8)	8 (5-8)	0.65
APGAR score (5 min)	8 (7-8)	8 (7-8)	0.28	7 (7-9)	8 (6-8)	0.29
APGAR score (1 min) <7 (%)	0	1 (2.5)	1.00	0	1 (4.5)	0.78
APGAR score (5 min) <7 (%)	0	0	1.00	0	1 (4.5)	0.78

Values are mean±SD, median (range) or percentage format. *P values are statistically significant. NFA=No fetal acidosis, FA=Fetal acidosis, UA=Umbilical artery, UV=Umbilical vein, PO2=Oxygen partial pressure, PCO2=Carbon dioxide partial pressure, SD=Standard deviation

Acid–base nomogram was constructed for both the groups which depicted that air group was nearer to acute respiratory acidosis region compared to oxygen group, further supporting that air group had more acute respiratory acidosis with significantly higher PCO2 levels and UA bicarbonate levels to compensate for the higher PCO2 values observed in the air group [Figure 2].

Figure 2

Acid–base nomogram: Scatter diagram showing plot of umbilical arterial pH against umbilical arterial bicarbonate levels and umbilical arterial carbon dioxide partial pressure for both air and oxygen groups. Babies of mothers who breathed air were nearer to the acute respiratory acidosis region compared to the oxygen group; as evident from the polynomial trend line for air (blue color) which is going more toward the upper right quadrant

DISCUSSION

Supplemental oxygen is used in obstetrics because pregnant women carry a high risk of hypoxemia. Due to the physiological and anatomical changes occurring in pregnancy, there are increase in maternal oxygen consumption and decrease in functional residual capacity.[16] Furthermore, after spinal anesthesia for CS, a significant deterioration in respiratory mechanics develops.[5] These conditions may cause fetal academia.[7] Supplementing oxygen will not prevent the problem but may help to improve oxygen delivery[8] and thus may benefit the fetus. However, the use of supplemental oxygen for healthy pregnant women during CS under spinal anesthesia has been questioned and investigated. Results of the previous studies demonstrated different and inconsistent results. Some studies reported improvement in the umbilical blood gases with high oxygen fractions,[1113] while other studies failed to detect similar improvement in UV oxygenation and umbilical blood gases.[517] On the other hand, high FiO2 was found to be associated with increase in oxygen-free radical activity in both mother and fetus in elective CS under spinal anesthesia.[11]

In our study, we observed higher pH values along with lower PCO2 in both UA and UV blood in mothers who received supplemental oxygen, and proportion of FA was also significantly less in those who received oxygen compared to the mothers who did not receive oxygen. Bicarbonate levels in UA and venous blood were higher for air group than that for oxygen group to compensate for a higher UA and UV PCO2 in air group. Furthermore, in subjects with FA, UA pH was significantly higher in mothers who received supplemental oxygen than air group. In spite of the above findings, we found no significant differences in neonatal outcome clinically in terms of APGAR score. The possible explanation might be that APGAR scores can detect only gross changes in clinical parameters.

Siriussawakul et al. studied the effect of supplementary oxygen and opined that oxygen supplementation helps when there is desaturation in mother during CS.[2] Van de Velde opined that supplementing oxygen to mother is not necessary and there is no better outcome for fetus.[18] Khaw et al. carried out a study in 2002 and that randomized controlled trial revealed that hyperoxia may occur after supplemental oxygen-induced oxygen-free radical activity.[11] A systematic review of 11 trials (conducted between 1982 and 2011) was performed by Chatmongkolchart and Prathep and they found no convincing evidence that giving supplementary oxygen to healthy term pregnant women during elective CS under regional anesthesia is either beneficial or harmful for either the mother or the fetus’ short-term clinical outcome as assessed by APGAR scores. However, they also said that the results should be interpreted with caution due to the low grade quality of the evidence.[1920]

Major limitations of our study were that we have not investigated maternal and fetal cord bloods to identify reactive oxygen species as tests were not available in our institute. However, clinical effect of increased reactive oxygen species on fetus has not yet been demonstrated.[911] Furthermore, we have not followed up and investigated the long-term effect of intrauterine hypoxia on the developmental progress of the baby.

CONCLUSIONS

Our findings demonstrate that administration of supplemental low-dose oxygen during elective CS under spinal anesthesia has potential benefit as demonstrated by less proportion of FA and better UA and UV blood pH status in mothers receiving supplemental oxygen compared to those who did not receive oxygen.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.