Archives of Gynecology and Obstetrics

, Volume 290, Issue 1, pp 21–34

Update on best available options in obstetrics anaesthesia: perinatal outcomes, side effects and maternal satisfaction. Fifteen years systematic literature review

Authors

    • Department of Woman and Child HealthUniversity of Padua
    • Dipartimento della Salute della Donna e del BambinoU.O.C di Clinica Ginecologica e Ostetrica
  • Marco Noventa
    • Department of Woman and Child HealthUniversity of Padua
  • Simone Fagherazzi
    • Department of Woman and Child HealthUniversity of Padua
  • Laura Lamparelli
    • Department of Woman and Child HealthUniversity of Padua
  • Emanuele Ancona
    • Department of Woman and Child HealthUniversity of Padua
  • Stefania Di Gangi
    • Department of Woman and Child HealthUniversity of Padua
  • Carlo Saccardi
    • Department of Woman and Child HealthUniversity of Padua
  • Donato D’Antona
    • Department of Woman and Child HealthUniversity of Padua
  • Giovanni Battista Nardelli
    • Department of Woman and Child HealthUniversity of Padua
Review

DOI: 10.1007/s00404-014-3212-x

Cite this article as:
Gizzo, S., Noventa, M., Fagherazzi, S. et al. Arch Gynecol Obstet (2014) 290: 21. doi:10.1007/s00404-014-3212-x

Abstract

Purpose

In modern obstetrics, different pharmacological and non-pharmacological options allow to obtain pain relief during labour, one of the most important goals in women satisfaction about medical care. The aim of this review is to compare all the analgesia administration schemes in terms of effectiveness in pain relief, length of labour, mode of delivery, side effects and neonatal outcomes.

Methods

A systematic literature search was conducted in electronic databases in the interval time between January 1999 and March 2013. Key search terms included: “labour analgesia”, “epidural anaesthesia during labour” (excluding anaesthesia for Caesarean section), “epidural analgesia and labour outcome” and “intra-thecal analgesia”.

Results

10,331 patients were analysed: 5,578 patients underwent Epidural-Analgesia, 259 patients spinal analgesia, 2,724 combined spinal epidural analgesia, 322 continuous epidural infusion (CEI), 168 intermittent epidural bolus, 684 patient-controlled infusion epidural analgesia and 152 intra-venous patient-controlled epidural analgesia. We also considered 341 women who underwent patient-controlled infusion epidural analgesia in association with CEI and 103 patients who underwent patient-controlled infusion epidural analgesia in association with automatic mandatory bolus.

Conclusion

No significant differences occurred among all the available administration schemes of neuraxial analgesia. In absence of obstetrical contraindication, neuraxial analgesia has to be considered as the gold standard in obtaining maternal pain relief during labour. The options available in the administration of analgesia should be known and evaluated together by both gynaecologists and anaesthesiologists to choose the best personalized scheme and obtain the best women satisfaction. Since it is difficult to identify comparable circumstances during labour, it is complicate to standardize drugs schemes and their combinations.

Keywords

Epidural analgesiaLabour painMaternal satisfactionNeuraxial analgesiaPharmacological schemes

Introduction

Nowadays, it is known that painful labour produces adverse changes in maternal physiology and biochemistry with subsequent effects on the baby. In absence of a medical contraindication, maternal request is a sufficient indication for pain relief during labour: it is considered unacceptable to let an individual experience pain when it is possible to avoid with safe medical assistance.

In modern obstetrics, different pharmacological and non-pharmacological options allow to obtain pain relief during labour, one of the most important goals in women satisfaction about medical care. [1, 2]

Even if non-pharmacological options are still debated and not universally accepted, universal guidelines consider both epidural and spinal analgesia (SA) (neuraxial techniques) the gold standard in pain relief during labour [1].

Both methods are classified into the group of loco-regional analgesia since pain relief is limited to the specific anatomical region linked to the axial portion desensitized by the injected drug [3].

To date, Epidural nerve block is widely used for labour analgesia because of its effective pain relief, reduced maternal stress response, improved parturient satisfaction, and potential ability to provide anaesthesia.

Loco-regional analgesia can be administrated using epidural and spinal approaches (alone or in combination) with different drug associations [4, 5].

In developed countries, the most used approach is the epidural analgesia (EA), despite its administration rate and pharmacological schemes greatly differ depending on anaesthesiologist experiences, available sources and local guidelines [6].

The modern trend in considering epidural analgesia as the first option in pain relief during labour seems to be due to its advantages such as possibility of utilizing the inserted catheter for further dose administration both during labour and in post-partum period, maternal self-administered pain relief, absence of significant neuromuscular block, and finally a lower drug dose in comparison to the spinal approach [7].

Nowadays, many options differing for drugs schemes and pharmacological associations are available to perform EA [812].

The aim of this review is to compare all the analgesia administration schemes in terms of effectiveness in pain relief, length of labour, mode of delivery, side effects and neonatal outcomes.

Data sources

A systematic literature search was conducted in electronic databases MEDLINE, EMBASE, Sciencedirect and the Cochrane Library in the interval time between January 1999 and March 2013 that we considered as a reasonable period to systematically review the most recent options for labour analgesia.

We considered only articles in English language. All original descriptions, case series, retrospective evaluations and review articles comparing or describing maternal outcomes (as patients general features, parity, length of labour, trends in cervical dilatation, mode of delivery), incidence of drug side effects (as hypotension, pruritus and nausea), VAS (visual analogue scale) values at three different interval time [T0 (at the time of drug administration), T1 (after the time of administration until to 30 min), T2 (30–120 min)] and, finally, maternal satisfaction were included. Concerning the new borns, pH and Apgar score (at first and fifth minute after delivery) were recorded.

Key search terms included: “labour analgesia”, “epidural anaesthesia during labour” (excluding anaesthesia for Caesarean section), “epidural analgesia and labour outcome” and “intra-thecal analgesia”.

A manual search of reference lists of included studies and review articles was successively performed. References of the retrieved articles were analysed to identify any work missed by the initial search.

The research was conducted independently by two reviewers with a double-blind modality and finally the results were matched to eliminate doubles.

We excluded studies providing ambiguous or insufficient data on procedure or following outcomes.

We also excluded studies that compared different analgesic drug combinations for each technique.

Available methods

Epidural analgesia

Before the epidural catheter placement, women usually receive an intravenous infusion of 500 mL lactated Ringer’s solution. Patient is kept in a lateral decubitus or sitting position. An anaesthesiologist inserts a 3 cm diameter epidural catheter within the epidural space in the L2-3 or L3-4 interspace via a 17-gauge-Tuohy-needle using a loss-of-resistance-to-air technique. Patient is then turned to the supine position with left uterine displacement. After the aspiration of the catheter and the check for blood or cerebrospinal fluid, each woman initially receives 3 mL of drug solution. If there is no sign of systemic effect after 3 min, the rest of the drug solution is injected over 1 min [13].

Spinal analgesia

This technique is performed by the classic lumbar puncture, generally with patients seated and bent forward, using a 25-gauge-cone-tipped needle. Once the dura-mater has been punctured and backflow is evident, the injection syringe should be attached to the needle, the mixture injected, and the needle withdrawn [14].

Combined spinal and epidural anaesthesia (CSEA)

This technique involves both spinal and epidural drug administration for pain relief combining a rapid and reliable onset of profound analgesia, resulting from spinal injection, with the flexibility and longer duration of epidural techniques. Many alternative techniques have been described, but normally an epidural needle is first used to identify the epidural space at the level of the third lumbar vertebra. A smaller diameter and longer needle is then passed through the epidural needle lumen piercing the dura and arachnoid to allow administration of analgesic medications (usually opioids) into the cerebrospinal fluid. The spinal needle is then removed and an epidural catheter is placed and secured in the normal way. Further analgesia, usually in the form of a low-dose local anaesthetic solution combined with an opioid, is then provided through the epidural catheter [1517].

Continuous epidural infusion (CEI)

This technique consists in a continuous infusion of analgesics into the epidural space. The infusion may be adjusted to achieve optimal analgesia for each parturient and additional rescue doses may be administered, if needed. A disadvantage of this technique is that the likelihood of motor block increases with prolonged infusion, even when relatively low doses of local anaesthetics are administered [9, 10].

Intermittent epidural bolus (IB)

Prior to the availability of microprocessor-controlled infusion pumps, IB was the most traditional technique used to achieve analgesia during labour. It consists in the anaesthetic on-demand infusion to maintain the pain relief. A catheter is sited in the epidural space and doses of local anaesthetic are injected timed to parturient complaints of pain, or at regular intervals (set on dose lasting). Main limitations are high possibility of bad timing in drug administration that may allow an incomplete analgesia and require frequent clinicians interventions [18].

Patient-controlled infusion (PCEA) and intra-venous patient-controlled epidural analgesia (IVPCA)

In these techniques, the administration of analgesic drug occurs in the epidural space using intermittent boluses as firstly described by Gambling et al. [19]. This technique utilizes a demand button through which the mother self-administers a prefixed dose of epidural medication whenever she experiences pain. This is a way to give the parturient the psychological advantage of being in control of their own therapy. Some clinicians advocate the use of a continuous background infusion with superimposed PCEA, others use a “pure” demand-only PCEA approach. The IVPCA involved the therapeutic scheme describing EA with an association of intra-venous analgesic drug administration [12, 20, 21].

Results

In the considered interval time, on the basis of our key search, more than 120 articles were available in the scientific literature database but only 43 satisfied our selection criteria. Among these, 20 studies were excluded since they aimed to compare different analgesic drug schemes for each technique, but they did not consider different techniques.

The remaining 23 studies [1, 6, 811, 20, 2238] were eligible for our data analysis.

A total of 10,331 patients were analysed: 5,578 patients underwent EA, 259 patients underwent SA, 2,724 underwent CSEA, 322 underwent CEI, 168 underwent IB, 684 underwent PCEA and 152 underwent IVPCEA. We also considered 341 patients who underwent PCEA in association with CEI and 103 patients who underwent PCEA in association with automatic mandatory bolus (AMB).

Patients were comparable for age (28.6 years; range 27.3–31.5) cervical dilatation (3.6 cm; range 3–4), BMI (28.3; range 26.5–29.2) and gestational age (39.1 week; range 38.9–39.6). All detailed data are shown in Table 1.
Table 1

A comparison of general features between all studies population reviewed

References

Year

Patients

Total

Age*

Mean (range)

Gest. age*

Mean (range)

BMI*

Mean (range)

Cervical dilatationa

Mean (range)

PCEA

 Boutros [10]

1999

50

684

30

28.7 (24.3–32)

39.6

39.4 (38–40)

27.8

26.9 (24–30.5)

3.4 (3–4)

 Halpren [22]

2004

124

28

40

28.3

4

 Halonen [6]

2004

86

28

40

24.8

3.6

 Saito [23]

2005

29

29

39.7

24.2

4

 Bremerich [24]

2005

33

30

27.3

3

 Chen [9]

2006

81

30

39

27.9

3

 Vallejo [25]

2007

63

29

39.2

30.5

3.5

 Okutomi [26]

2009

33

32

39

24

3

 Haydon [27]

2011

84

24.3

39.4

3.6

 Brogly [28]

2011

20

31

40

26.3

 Srivastava [29]

2012

30

25

38

 Sia [8]

2013

51

28.2

3.2

PCEA + CEI

 Bremerich [24]

2005

33

341

30

27.3 (24–31)

38.9 (38–40)

27.6

27.5 (23.6–31.6)

3

3.2 (3–3.5)

 Vallejo [25]

2007

64

29

39.1

31.6

3.4

 Sia [30]

2007

21

3

 Okutomi [26]

2009

33

31

39

23.6

3

 Leo [31]

2010

31

27.4

3.2

 Singh [20]

2011

30

24.4

38.2

3.5

 Haydon [27]

2011

87

24.9

39.5

3.4

 Brogly [28]

2011

17

28

40

27.4

 Srivastava [29]

2012

25

24

38

PCEA + AMB

 Sia [30]

2007

21

103

26.9 (–)

3

3.0 (2.9–3.2)

 Leo [31]

2012

31

26.6

2.9

 Sia [8]

2013

51

27.3

3.2

CEI

 Boutros [10]

1999

50

322

29.8

28.3 (25–30)

39.3

39.1 (39.2–39.7)

27.1

28.1 (24.9–31.6)

3.2 (3–3.6)

 Saito [23]

2005

29

30

39.3

24.9

3

 Chen [9]

2006

98

29

38.8

29

3

 Vallejo [25]

2007

62

27.8

39.2

31.6

3.3

 Haydon [27]

2011

83

25

39.3

3.6

IB

 Boutros [10]

1999

48

168

29.5

27.7 (24.8–29)

39.7

39.3 (38.4–40)

26.1

26.5 (–)

3.6 (–)

 Halonen [6]

2004

90

29

40

26.9

3.8

 Singh [20]

2011

30

24.8

38.4

3.4

EA

 Wilson [32]

2001

524

5,578

30

29.0 (24–31)

41

39.6 (38.9–41)

25.5

27.7 (25.5–29.7)

3.7 (2.3–5)

 Sezer [33]

2007

20

24

39.7

25.9

2.3

 Volmanen [1]

2008

21

28

28.2

4

 Miro [11]

2008

4,533

30.3

38.9

28.1

5

 Douma [34]

2011

10

31

28.2

3.6

 Pascual-Ramirez [35]

2011

72

31

39

28.6

 Gambling [36]

2013

398

29

39.4

29.7

3.7

CSEA

 Wilson [32]

2001

266

2,724

30

28.6 (24–30.8)

41

39.4 (38.9–41)

24.6

27.4 (24.6–29.2)

3.0 (2.5–3.7)

 Sezer [33]

2007

20

24

39

27.1

2.5

 Miro [11]

2008

1,964

30.8

38.9

28.1

3

 Pascual-Ramirez [35]

2011

72

29

39

27.9

 Gambling [36]

2013

402

29

39.4

29.2

3.7

IVPCA

 Halpren [22]

2004

118

152

27

28.9 (27–32.7)

39

39 (–)

28.3

29.2 (28.3–29.8)

4

4.0 (4–4.2)

 Volmanen [1]

2008

24

27

29.6

4

 Douma [34]

2011

10

32.7

29.8

4.2

SA

 Viitanen [37]

2005

229

259

31

31.5 (31–32)

39.4

39.3 (–)

29.4

29.2 (–)

 

 Rofaeel [38]

2007

30

32

39.2

29

Age is expressed in years, BMI in kg/m2, gestational age in weeks, cervical dilatation in cm

PCEA patient-controlled infusion epidural analgesia, PCEA + CEI patient-controlled infusion epidural analgesia + continuous epidural infusion, PCEA +AMB patient-controlled infusion epidural analgesia + automatic mandatory bolus, CEI continuous epidural infusion, IB intermittent epidural bolus, EA epidural analgesia, CSEA combined spinal epidural analgesia, IVPCA intra-venous patient-controlled epidural analgesia, SA spinal analgesia

Epidural analgesia

Seven studies analysed the EA efficacy; among them five [13, 32, 33, 35, 36] compared EA versus CSEA and two [1, 34] compared EA versus IVPCA. Six studies [1, 11, 3336] reported data about parity with a mean primiparous women percentage of 65 % (36–100 %). Considering the labour length, we found a mean value of 294 min (range 240–442 min). Data about the mode of delivery showed that vaginal delivery occurred in 69 % of the cases (range 36–90 %), operative delivery in 15 % (range 0–40 %) and caesarean section in 15 % (range 5–26 %).

Only five studies [1, 3336] reported Apgar score at the 1st and 5th minute with a score less than 7, respectively, in 5.8 % (range 0–25 %) and 2 % (0–13 %) of the babies. Only two studies [1, 34] reported pH values with mean value of 7.21 and 7.19, respectively.

Concerning drugs side effects, only one study [35] reported data about the hypotension rate (2.80 %), three studies [11, 33, 35] reported data about the pruritus (8.8 %; range 0–20.8 %) and five studies reported data about nausea (9.3 %; range 5–20 %) [1, 11, 3335].

Only two studies [33, 34] reported VAS values at T0 (mean value of 9.8), T1 (mean value of 1.2) and T2 (mean value of 2.1). Only one study [35] reported higher maternal satisfaction in EA versus CSEA. All detailed data are shown in Tables 2 and 3.
Table 2

Comparison of maternal/foetal obstetrical outcomes, side effects and satisfaction between eligible studies

References

Year

Primiparous (%)

Labour duration

Vaginal delivery (%)

Operative delivery (%)

Caesarean section (%)

Apgar 1 < 7 (%)

Apgar 5 < 7 (%)

pH

Hypotension (%)

Pruritus (%)

Nausea

T0

T1

T2

Maternal satisfaction

PCEA

 Boutros [10]

1999

240

77

17

6

2

2

2

23

7

0

2

 Halpren [22]

2004

100

61

29

10

17

3

7.24

>In PCEA

 Halonen [6]

2004

220

71

12.8

16.03

6

 Saito [23]

2005

100

390

45

54

0

0

0

7.29

0

7

3

>In PCEA

 Bremerich [24]

2005

52

100

0

0

3

0

7.28

9

3

 Chen [9]

2006

75

0

14.80

0

Equal

 Vallejo [25]

2007

51

280

81

5

14

2

0

Equal

 Okutomi [26]

2009

630

28

72

0

0

0

7.28

0

73

3

 Haydon [27]

2011

480

69

3.5

26

5

4

 Brogly [28]

2011

385

70

20

10

8

4

2

Equal

 Srivastava [29]

2012

46

349

80

0

20

0

7

2

Equal in PCEA + CEI

 Sia [8]

2013

100

414.2

63

16

22

0

2

52.90

2

>In PCEA + AMB

PCEA + CEI

 Bremerich [24]

2005

70

100

0

0

3

2

9

6

Equal

 Vallejo [25]

2007

47

294

81

5

14

3

0

Equal

 Sia [30]

2007

100

313

76

9

15

10

52

5

Equal

 Okutomi [26]

2009

560

30

70

0

0

0

7

0

61

0

 Leo [31]

2011

43.30

348

86.60

0

13.30

3

9

2

>In PCEA + CEI

 Singh [20]

2011

500

62

9.30

28

3

3

 Haydon [27]

2011

355

59

6

35

 

9

3

1

 Brogly [28]

2012

100

422

51.60

19.40

29

0

6.50

61.30

0

>In PCEA + AMB

 Srivastava [29]

2012

44

142

84

0

16

0

8

2

Equal in PCEA + CEI

PCEA + AMB

 Sia [30]

2007

100

375

61

5

34

19

43

9

Equal

 Leo [31]

2012

100

443

67.70

6.50

25.80

0

3.20

71

6.50

>In PCEA + AMB

 Sia [8]

2013

100

389

64.7

9.8

25.5

0

0

56.90

2

>In PCEA + AMB

CEI

 Boutros [10]

1999

220

84

10

6

4

2

4

12

7

0

1

 Saito [23]

2005

100

320

55

10

31

3

2

>In PCEA

 Chen [9]

2006

90

6

15

2

0

Equal

 Vallejo [25]

2007

53

342

79

0

10

0

Equal

 Haydon [27]

2011

500

59

45

0

0

0

7.3

0

7

0

IB

 Boutros [10]

1999

270

83

11

6

6

2

2

6

6

0

1

 Halonen [6]

2004

100

220

73.30

20

6.70

5

 Singh [20]

2011

43.30

331

90

0

10

3

9

3

>In PCEA + CEI

EA

 Wilson [32]

2001

36.0

35.20

26.00

 

 Sezer [33]

2007

100

270

80.0

0.00

20.00

0.00

0.00

0.00

5.00

9

1

2

 Volmanen [1]

2008

76

240

90.0

5.00

5.00

0.00

7.21

9.50

 Miro [11]

2008

65.60

300

82.4

8.30

9.30

20.80

6.20

 Douma [34]

2011

70

442

40.0

40.00

20.00

25.00

13.00

7.19

20.00

8

2

1

 Pascual-Ramirez [35]

2011

36

246

79.2

5.60

14.10

0.00

0.00

2.80

5.60

5.60

>Only EA

 Gambling [36]

2013

45

270

72.7

13.10

14.10

4.30

0.30

 CSEA

                

 Wilson [32]

2001

41.0

28.90

30.10

 Sezer [33]

2007

100

299

80.0

0.00

20.00

0.00

0.00

60

10

9

1

1

 Miro [11]

2008

48

180

71.7

11.70

16.60

10

9

 Pascual-Ramirez [35]

2011

34.70

255

75.0

2.80

21.10

0.00

0.00

2.80

25.30

11.20

>Only EA

 Gambling [36]

2013

50

300

73.2

11.00

15.80

4.20

0.20

IVPCA

 Halpren [22]

2004

100

69

21

10.20

28

4

7.23

>In PCEA

 Volmanen [1]

2008

71

79

17

4

0

0

7.25

37.50

 Douma [34]

2011

50

559

70

10

20

14

0

7.14

50

8

5

6

SA

 Viitanen [37]

2005

0

343

88.1

1.40

0.50

2

0.50

2

64

0.5

 Rofaeel [38]

2007

73.4

6.6

20

23.30

33.30

3.3

PCEA patient-controlled infusion epidural analgesia, PCEA + CEI patient-controlled infusion epidural analgesia + continuous epidural infusion, PCEA +AMB patient-controlled infusion epidural analgesia + automatic mandatory bolus, CEI continuous epidural infusion, IB intermittent epidural bolus, EA epidural analgesia, CSEA combined spinal epidural analgesia, IVPCA intra-venous patient-controlled epidural analgesia, SA spinal analgesia

aData about maternal/foetal outcomes are expressed in rate (mean or weighted mean value)

Table 3

A detailed comparison of drug combinations between all neuraxial schemes reviewed in study population

References

Year

Comparison of techniques

Drugs schemes

PCEA

 Boutros [10]

1999

PCEA vs IB vs CEI

Bupivacaine 0.125 % + sufentanil 0.5 mcg/mL

 Halpren [22]

2004

PCEA vs IVPCEA

0.08 % Bupivacaine + fentanyl 1.6 mcg/mL

 Halonen [6]

2004

PCEA vs IB

20 mcg of bupivacaine + 75 mcg of fentanyl vs 14 mcg of bupivacaine + 60 mcg of fentanyl

 Saito [23]

2005

PCEA vs CEI

0.1 % Ropivacaine + fentanyl 2 mcg/mL

 Bremerich [24]

2005

PCEA vs PCEA + CEI

Ropivacaine 0.16 % + sufentanil 0.5 mcg/mL

 Chen [9]

2006

PCEA vs CEI

Bupivacaine 0.625 mg/mL + fentanyl 2 mcg/mL

 Vallejo [25]

2007

PCEA vs CEI vs PCEA + CEI

0.1 % Ropivacaine (10 mL) + fentanyl (100 mcg)

 Okutomi [26]

2009

PCEA vs PCEA + CEI

0.1 % Ropivacaine + fentanyl 2 mcg/mL

 Haydon [27]

2011

PCEA vs CEI vs PCEA + CEI

0.1 % Bupivacaine + 2 mcg/mL fentanyl

 Brogly [28]

2011

PCEA vs PCEA + CEI

0.125 % Levobupivacaina + 1.5 mcg/mL fentanyl

 Srivastava [29]

2012

PCEA vs PCEA + CEI

0.125 % Bupivacaina + fentanyl

 Sia [8]

2013

PCEA vs PCEA + AMB

0.1 % Ropivacaine + fentanyl 2 mcg/mL

PCEA + CEI

 Bremerich [24]

2005

PCEA + CEI vs PCEA

Ropivacaine 0.16 % + sufentanil 0.5 mcg/mL

 Vallejo [25]

2007

PCEA + CEI vs CEI vs PCEA

0.1 % Ropivacaine (10 mL) + fentanyl (100 mcg)

 Sia [30]

2007

PCEA + CEI vs PCEA + ABM

0.1 % Ropivacaine + fentanyl 2 mcg/mL

 Okutomi [26]

2009

PCEA + CEI vs PCEA

0.1 % Ropivacaine + fentanyl 2 mcg/mL

 Leo [31]

2011

PCEA + CEI vs PCEA + AMB

10 mL of 0.1 % bupivacaine + 50 mcg fentanyl

 Singh [20]

2011

PCEA + CEI vs IB

0.1 % Bupivacaine + 2 mcg/mL fentanyl

 Haydon [27]

2011

PCEA + CEI vs PCEA vs CEI

0.125 % Levobupivacaina + 1.5mcg/mL fentanyl

 Brogly [28]

2012

PCEA + CEI vs PCEA + AMB

0.1 % Ropivacaine + fentanyl 2 mcg/mL

 Srivastava [29]

2012

PCEA + CEI vs PCEA

0.125 % Bupivacaina + fentanyl

PCEA + AMB

 Sia [30]

2007

PCEA + ABM vs PCEA + CEI

0.1 % Ropivacaine + fentanyl 2 mcg/mL

 Leo [31]

2011

PCEA + AMB vs PCEA + CEI

0.1 % Ropivacaine + fentanyl 2 mcg/mL

 Sia [8]

2013

PCEA + AMB vs PCEA

0.1 % Ropivacaine + fentanyl 2 mcg/mL

CEI

 Boutros [10]

1999

CEI vs PCEA vs IB

Bupivacaine 0.125 % + sufentanil 0.5 mcg/mL

 Saito [23]

2005

CEI vs PCEA

0.1 % Ropivacaine + fentanyl 2 mcg/mL

 Chen [9]

2006

CEI vs PCEA

Bupivacaine 0.625 mg/mL + fentanyl 2 mcg/mL

 Vallejo [25]

2007

CEI vs PCEA + CEI vs PCEA

0.1 % Ropivacaine (10 mL) + fentanyl (100 mcg)

 Haydon [27]

2011

CEI vs PCEA + CEI vs PCEA

0.1 % Bupivacaine + 2 mcg/mL fentanyl

IB

 Boutros [10]

1999

IB vs CEI vs PCEA

Bupivacaine 0.125 % + sufentanil 0.5 mcg/mL

 Halonen [6]

2004

IB vs PCEA

20 mcg of bupivacaine + 75 mcg of fentanyl vs 14 mcg of bupivacaine + 60 mcg of fentanyl

 Singh [20]

2011

IB vs PCEA + CEI

10 mL of 0.1 % bupivacaine + 50 mcg fentanyl

EA

 Wilson [32]

2001

EA vs CSEA

0.1 % Bupivacaine + fentanyl 2 mcg/mL

 Sezer [33]

2007

EA vs CSEA

0.1 % Bupivacaine + fentanyl 50 mcg

 Volmanen [1]

2008

EA vs IVPCEA

20 mL levobupivacaine 0.625 mg/mL + fentanyl 2 mcg/mL

 Miro [11]

2008

EA vs CSEA

0.2 % Ropivacaine + fentanyl 50 mcg

 Douma [34]

2011

EA vs IVPCEA

0.1 % Ropivacaine + sufentanil 0.5 mcg/mL

 Pascual-Ramirez [35]

2011

EA vs CSEA

2.5 mg of bupivacaine + 25 μg of fentanyl + 200 μg of morphine

 Gambling [36]

2013

EA vs CSEA

0.125 % Bupivacaine + 2 μg/mL fentanyl

CSEA

 Wilson [32]

2001

CSEA vs EA

0.1 % Bupivacaine + fentanyl 2 mcg/mL

 Sezer [33]

2007

CSEA vs EA

0.1 % Bupivacaine + fentanyl 50 mcg

 Miro [11]

2008

CSEA vs EA

0.2 % Ropivacaine + fentanyl 50 mcg

 Pascual-Ramirez [35]

2011

CSEA vs EA

2.5 mg of bupivacaine + 25 μg of fentanyl + 200 μg of morphine

 Gambling [36]

2013

CSEA vs EA

0.125 % Bupivacaine + 2 μg/mL fentanyl

IVPCEA

 Halpren [22]

2004

IVPCEA vs PCEA

0.08 % Bupivacaine + fentanyl 1.6 mcg/mL

 Volmanen [1]

2008

IVPCEA vs EA

20 mL levobupivacaine 0.625 mg/mL + fentanyl 2 mcg/mL

 Douma [34]

2011

IVPCEA vs EA

0.1 % Ropivacaine + sufentanil 0.5 mcg/mL

SA

 Viitanen [37]

2005

2.5 mg Bupivacaine + 25 mcg fentanyl

 Rofaeel [38]

2007

2.5 mg of hyperbaric or plain bupivacaine + 15 μg of fentanyl

PCEA patient-controlled infusion epidural analgesia, PCEA + CEI patient-controlled infusion epidural analgesia + continuous epidural infusion, PCEA + AMB patient-controlled infusion epidural analgesia + automatic mandatory bolus, CEI continuous epidural infusion, IB intermittent epidural bolus, EA epidural analgesia, CSEA combined spinal epidural analgesia, IVPCA intra-venous patient-controlled epidural analgesia, SA spinal analgesia

Spinal analgesia

Only two eligible studies [37, 38] reported data about outcomes after SA. All detailed data are shown in Tables 2 and 3.

Combined spinal and epidural anaesthesia

Five studies reported data about CSEA outcomes obtained by the comparison with EA. [11, 32, 33, 35, 36] Four of them [11, 33, 35, 36] reported data about parity with a percentage of primiparous of 58 % (range 34.7–100 %). Considering the labour length we found a mean value of 258 min (range 180–300). Vaginal delivery occurred in 68 % of the cases (range 41–80 %), operative delivery in 11 % (range 0–29 %) and caesarean section in 21 % (range 16–30 %). Three studies [33, 35, 36] reported data about Apgar score at the 1st and 5th minute with a mean weighted percentage of babies with a score less than 7 in 1.4 % (range 0–4.2 %) and 0 % (0–0.2 %) of the cases, respectively. No study reported data about pH values.

Concerning drugs side effects, only one study [35] reported a hypotension rate of 2.80 % (similar to EA), three studies [11, 33, 35] reported a pruritus rate of 31.7 % (range 10–60 %) and three studies reported a nausea rate of 10 % (range 9–11.2 %) [11, 33, 35].

Only one study [33] reported a VAS value of 9 at T0, 1 at T1 and 1 at T2. Only one study [35] reported higher maternal satisfaction in EA versus CSEA.

All detailed data are shown in Tables 2 and 3.

Continuous epidural infusion

Five studies analysed the efficacy of CEI. Among them, two studies [25, 27] compared CEI, PCEA + CEI, and PCEA, two studies [9, 23] compared CEI versus PCEA and one [10] compared CEI, PCEA and IB.

Two studies [23, 25] reported data about parity with nulliparous rate of 53 and 100 %, respectively.

The mean length of labour in the studies was 345 min (range 220–500). Data about the mode of delivery showed that vaginal delivery occurred in 73.4 % of the cases (range 55–90 %), operative delivery in 14.2 % (range 0–45 %) and caesarean section in 12.4 % (range 16–30 %). Four studies [9, 10, 23, 27] reported data about Apgar score at the 1st and at 5th minute with a mean percentage of babies with a score less than 7 in 2.2 % (range 0–4 %) and 0.8 % (range 0–2 %) of the cases. Only one study [27] reported pH values at birth with a mean value of 7.3. Concerning drugs side effects, only two studies [10, 27] reported a hypotension rate of 2 % (range 0–4 %), two studies [10, 27] reported a pruritus rate of 9.5 % (range 7–12 %) and only one did no report nausea in any case. Only one study [10] reported data about VAS with a value of 7 at T0, 0 at T1 and 1 at T2. Two studies [9, 25] reported equal maternal satisfaction for all used techniques and one [23] reported higher satisfaction with PCEA.

All detailed data are shown in Tables 2 and 3.

Intermittent epidural bolus

Three studies analysed the efficacy of IB, among them one [10] compared IB, PCEA and CEI, one [20] compared IB versus PCEA + CEI and one [6] compared IB versus PCEA. Two studies [6, 20] reported data about parity with primiparous percentage of 43 and 100 %, respectively. Considering the length of labour, we found a mean value of 273 min (range 220–331). Data about mode of delivery showed that vaginal delivery occurred in 82 % (range 73–90 %), operative delivery in 10 % (range 0–20 %) and caesarean section in 7.5 % (range 6–10 %) of the cases. Two studies [10, 20] reported Apgar score at the 1st minute with a percentage of babies with a score less than 7 in 6 and 3 % of the cases, respectively; two studies [6, 10] reported Apgar score at 5th minute with a percentage of babies with a score less than 7 in 2 and 5 % of the cases, respectively. No study reported data about pH values.

Concerning drugs side effects, only one study [10] reported a hypotension rate of 2 % and one [10] a pruritus rate of 6 %. No study reported data about nausea. Only two studies [10, 20] reported VAS values with mean value of 6 and 9 at T0, of 0 and 3 at T1, of 1 and 3 at T2.

Only one study [20] reported higher maternal satisfaction as higher in PCEA + CEI. All detailed data are shown in Tables 2 and 3.

Patient-controlled infusion

Twelve studies analysed the efficacy of PCEA. Among them, four [24, 26, 28, 29] compared PCEA versus PCEA + CEI, two [25, 27] compared PCEA versus CEI and PCEA + CEI, two [9, 26] compared PCEA versus CEI alone, one [6] compared PCEA versus IB, one [10] compared PCEA, IB and CEI, one [22] compared PCEA versus IVPCEA and one [8] PCEA versus PCEA + AMB.

Six studies [8, 2225, 29] reported data about parity, with primiparous percentage of 75 % (range 46–100 %). Considering labour length, we found a mean value of 376 min (range 220–630).

Data about the mode of delivery showed that vaginal delivery occurred in 68 % of the cases (range 28–100 %), operative delivery in 19 % (range 0–70 %) and caesarean section in 16 % (range 0–26 %). Seven studies [10, 2227] reported an Apgar score at 1st minute with a mean percentage of babies with a score less than 7 in 4 % (range 0–17 %) of the cases and eleven studies [6, 810, 2227, 29] considered Apgar at 5th minute reporting a percentage of babies with a score less than 7 in 1.3 % (range 0–6 %) of the cases.

Four studies [2224, 26] reported pH values with a weighted mean value of 7.27 (range 7.24–7.29). Concerning drugs side effects, four studies [8, 10, 23, 26] reported a hypotension rate of 1 % (range 0–2 %), five [8, 10, 23, 24, 26] a pruritus rate of 33 % (range 7–52 %) and four [8, 23, 24, 26] a nausea rate of 3 % (range 2–3 %). Only three studies [10, 28, 29] reported VAS values at T0 (7,8,7, respectively), at T1 (0,4,2, respectively) and at T2 (all reported value of 2).

Four studies [9, 25, 28, 29] reported equal maternal satisfaction rate among the different techniques: in three studies, the satisfaction rate was higher after PCEA [2224] and in one study [8] satisfaction was higher in PCEA + AMB. All detailed data are shown in Tables 2 and 3.

Intra-venous patient-controlled epidural analgesia (IVPCEA)

Three studies analysed the IVPCEA efficacy. Among them, two [1, 34] compared IVPCEA versus EA and one [22] compared IVPCEA versus PCEA. Data about parity reported a 74 % percentage (range 50–100 %) of primiparous women. Only one study reported about labour length, with a mean value of 559 min. Vaginal delivery occurred in 73 % of the cases (range 69–79 %), operative delivery in 16 % (range 10–21 %) and caesarean section in 11 % (range 4–20 %).

Apgar score less than 7 at the 1st and 5th minute was registered, respectively, in 14.4 % (range 0–28 %) and 1 % (0–4 %) of the patients. The mean neonatal pH values were 7.21 (range 7.14–7.25).

Concerning drugs side effects, none of the studies reported data about hypotension and pruritus while two [1, 34] reported nausea rate of 37.5 and 50 %, respectively. Data about VAS were described only in one study [34] and were 8 at T0, 5 at T11 and 6 at T2. Finally, in one study [22] higher maternal satisfaction after PCEA was reported.

All detailed data are shown in Tables 2 and 3.

Association between PCEA and CEI

Nine studies analysed the efficacy of PCEA plus CEI. Among them, three [24, 26, 29] compared PCEA + CEI versus PCEA; two [25, 27] PCEA + CEI, PCEA and CEI; three [28, 30, 31] PCEA + CEI versus PCEA + AMB and one [20] PCEA + CEI versus IB. Six studies [24, 25, 2831] reported data about parity with a mean primiparous percentage of 67 % (43.4–100 %). Considering labour length, we found a mean value of 366 min (range 142–560). Data about mode of delivery showed that vaginal delivery occurred in 70 % of the cases (range 30–100 %), operative delivery in 13 % (range 0–70 %) and caesarean section in 17 % (range 0–35 %).

Four studies [20, 2426] reported a weighted mean percentage of Apgar score less than 7 at the 1st minute in 2 % of the babies (range 0–3 %) and eight studies [20, 2426, 2831] reported data at 5th minute with a weighted mean percentage of the babies with an Apgar score less than 7 of 2 % (range 0–10 %). Only one study [26] reported neonatal pH values with a mean value of 7.29. Concerning drugs side effects, two studies [26, 28] reported a hypotension rate of 0 and 6.50 %, respectively, four studies [24, 26, 28, 30] a pruritus rate of 46 % (range 9–61 %) and four studies reported a nausea rate of 3 % (range 0–6 %). Three studies [27, 29, 31] reported VAS values with a mean value of 8.6 at T0 (range 8–9), 2 at T1 (range 1–3) and 2 at T2 (range 1–3). Four studies [24, 25, 29, 30] reported equal maternal satisfaction between all the techniques, one study [31] reported higher satisfaction with PCEA + CEI and one study [28] reported higher satisfaction with PCEA + AMB. All detailed data are shown in Tables 2 and 3.

Association between PCEA and AMB

Three studies analysed the efficacy of PCEA + AMB. Among them, two [30, 31] compared PCEA + AMB versus PCEA + CEI and one [8] compared PCEA + AMB versus PCEA.

All patients were primiparous. Studies reported a labour length of 402 min (range 375–443). Data about mode of delivery showed that vaginal delivery occurred in 64 % of the cases (range 61–67.7 %), operative delivery in 7 % (range 5–9.8 %) and caesarean section in 28 % (range 25.5–34 %). No studies reported data about Apgar score at the 1st minute while they reported values at 5th minute with a mean percentage of babies with a score less than 7 in 6 % of the cases (range 0–19 %). No study reported data about pH values.

Concerning drugs side effects, two studies [8, 31] reported a hypotension rate of 0 and 3.2 %, respectively, a pruritus rate of 57 % (range 43–71 %) and a nausea rate of 6 % (range 2–9 %). No study reported data about VAS values. One study [30] reported equal maternal satisfaction for all the compared techniques and in two studies [8, 31] women satisfaction was higher with PCEA + AMB. All detailed data are shown in Tables 2 and 3.

Discussion

Labour pain is probably the most severe pain that a woman experiences during her lifetime [39]. The possibility to obtain pain relief during labour is, therefore, an essential part of good obstetrical care.

Although severe pain is not life-threatening in healthy parturient, it can contribute to increase the percentage of neuropsychological consequences like postnatal depression [40] and post-traumatic stress disorder [41]. According to these evidences, it is clear that analgesia during labour is a basic component of a relaxed childbirth experience and may influence the subsequent pregnancy desire.

Pharmacological options to achieve pain relief are branched in two main groups according to the drugs administration way: systemic or loco-regional. Systemic drugs administration can be performed by intravenous, intramuscular, or inhalation path as well as loco-regional which can be performed by EA, SA or both together (CSEA).

Even if all techniques allow clinicians to perform analgesia according to maternal request, only EA and CSEA may offer the option of maternal self-controlled administration.

Differently from previous reviews that focused on different available drugs used in neuraxial analgesia (considering only few administration ways), the present manuscript is the first one that systematically compares all the available data on neuraxial options for intra-partum analgesia administration.

Anyway, if on one hand the performance of complete overview of all available options allows to evaluate a wide amount of data (increasing the strength of the results), on the other hand, the comparison of data from different populations (by studies evaluating different endpoints) receiving non-homogeneous drugs-schemes analgesia made very difficult both the data analysis and the achievement of a final key-message for the clinicians without intrinsic bias [42].

Another not under-estimable difficulty for our previous established endpoints is due to the attention of almost all eligible studies on “maternal pain relief and satisfaction” minimizing or avoiding informations about labour trend, perinatal outcome and early post-partum complications (such as bonding/breastfeeding failure and maternal depression).

The evidences about different administration ways of peri-partum analgesia are often conflicting and affected by misconceptions. Many studies, especially those with higher level of evidence (perspective and randomized), were conducted in a single Centre (where usually one technique is preferred to another one depending on Anaesthesiologist or Obstetrical preferences) and the endpoints were mostly settled on different drugs type and scheme more than the method of administration.

This may establish wrong convictions regarding maternal–foetal advantages or disadvantages linked to the method of administration. Multiple observational studies found that early stage of labour (considered as cervical dilatation <4 cm) represents a relative contraindication to perform EA, since it seems to be associated with a higher risk of caesarean delivery during labour [4345].

When this outcome was evaluated using data from all the available studies (5,578 patients), urgent caesarean section rate was about 15 % considering a mean cervical dilatation of about 3.5 cm at EA administration. Furthermore, these comforting results were confirmed also when different pharmacological combinations were considered and this fact seems to be sufficient to erase all doubts and debates in the era of 40 % caesarean section rate [46, 47].

Similar considerations can be made concerning operative delivery. The mean rate of operative delivery reported in studies evaluating patients receiving EA was 15 %, apparently higher than the one in the general population. Anyway, after critical evaluation of patients receiving EA, it is mandatory to underline that this percentage was influenced by a cohort of patients frequently affected by severe pain due to foetal malposition and macrosomia, both independent risk factors for dystocia, prolonged labour and operative delivery [4850].

Starting from these evidences, we can postulate that EA is a safe procedure to remove labour pain with a neutral balance between labour trend and delivery effects [5156].

Another important concept that has to be clarified is about the effects of intra-partum analgesia on neonatal reactivity. The analysis of the few selected manuscripts, reporting data about intra-partum analgesia using opioid drugs administered both via loco-regional and systemic analgesia, emphasized the risk of low neonatal reactivity, pH value and Apgar score at birth [22, 30, 34]. However, critical evaluation of data achieved by all the eligible studies confirmed the neonatal safety profile of neuraxial analgesia in all administration schemes, underlining that the cases of poor neonatal wellbeing were often reported in studies affected also by higher operative delivery rate [55].

Furthermore, additional confirmation of neonatal impairment absence due to intra-partum analgesia derives from the evidences of good early and late breastfeeding rate reported by the few manuscripts that consider this outcome [51]. Unfortunately concerning this concept, data are fragmentary and further studies are mandatory.

Certainly, the reassurance of intra-partum analgesia described by our study is affected by an intrinsic bias. We were not able to adjust our data (derived from a large number of heterogeneous manuscripts) according to different clinical practice and team experience (Anaesthesiologist, Perinatologist and Obstetric) resulting in both well-known and not under-estimable independent risk factors for neonatal well-being assessment.

Reporting good intra-partum analgesia profile in labour trend and neonatal outcomes independently from the administration way, our data permit to assume that maternal pain relief is a sufficient universally accepted condition to administer analgesia when requested.

The choice of the best way to offer pain relief should be tailored depending on the setting, the Anaesthesiologist’s experience, the Country economic development and the woman’s features.

Concerning women preference in choosing the intra-partum analgesia way, data did not permit to draw univocal conclusions, since a large part of evaluated studies, despite considered this as important endpoint, reported maternal satisfaction without use of standardized and quantifiable scales. In many cases, satisfaction rates were reported with sentences like “maternal satisfaction was higher…” therefore, they are not estimable.

The last but not the least for importance, the great majority of studies reported data about intra-partum analgesia administered in uncomplicated pregnancy, resulting in very poor evidences about analgesia effects in pregnancy affected by complications such as diabetes, preterm delivery, amniotic fluid alteration [49, 57, 58].

Similarly, a large part of these studies did not discuss the interaction between analgesia and some antepartum risk factors such as advanced maternal age [59] or post-partum complications such as uterine atony and post-partum haemorrhage [60, 61].

Finally, several studies were affected by bias due to the lack of data about maternal analgesia side effects. Even though it is universally accepted that neuraxial analgesia owns only few side effects, the rate of maternal hypotension, pruritus, nausea, hyperpyrexia cannot be underestimated.

Anyway, we found that there are no differences among the different techniques concerning hypotension (in the whole sample the reported weighted mean value was about 3 %), pruritus (weighted mean percentage of about 33 %) and nausea (weighted mean percentage of about 9 %) despite these side effects should be further investigated [6264].

Conclusions

Data obtained from large scale population in wide temporal range showed that no significant differences occurred among all the available administration schemes of neuraxial analgesia.

In absence of significant obstetrical contraindication neuraxial analgesia has to be considered as the gold standard in maternal pain relief during labour. The options available in analgesia administration should be known and evaluated by both gynaecologists and anaesthesiologists together to choose the best personalized scheme and to obtain the best women satisfaction.

Since it is difficult to identify comparable circumstances during labour it is complicate to standardize drugs schemes and their combinations.

Further large scale studies focused on the evaluation of maternal satisfaction will lead the clinicians to reach the primary purpose of intra-partum analgesia: safely eliminate pain during one of the most beautiful periods of women life.

Acknowledgments

The authors would like to thank equip of the Gynaecologic and Obstetric Clinic of Padua. All authors declare they have no funding.

Conflict of interest

All authors declare no conflicts of interest.

Copyright information

© Springer-Verlag Berlin Heidelberg 2014