Role of combined spinal epidural technique

The initiation of neuraxial labour analgesia using the combined spinal epidural (CSE) technique has gained popularity in recent years. CSE analgesia was initially introduced to reduce the adverse effects associated with traditional epidural analgesia and to improve maternal mobility. Compared with traditional epidural analgesia, the major advantage of CSE analgesia is the rapid onset of uniform analgesia. CSE analgesia reliably blocks both low thoracic and sacral nerve roots with minimal maternal and umbilical cord blood concentrations of analgesics because of the low doses of local anaesthesia and opioid required to initiate spinal analgesia . The CSE ‘needle-through-needle’ technique may improve the proper placement of a functioning epidural catheter; verification of placement of the spinal needle tip in the subarachnoid space by the return of the cerebrospinal fluid through the needle makes it highly likely that the tip of the epidural needle is correctly sited in the epidural space . The dural puncture may also allow subarachnoid transfer of epidurally administered drugs, potentially enhancing the spread of the block and the analgesic quality .

Despite the widespread use of this technique, CSE analgesia has not been shown to confer advantages compared with epidural analgesia in terms of obstetric or neonatal outcomes . A recent randomized double-blind trial found no differences between CSE and epidural analgesia in neonatal or obstetric outcomes, including foetal heart abnormalities . Interestingly, in a study using non-invasive cardiac output assessment, high baseline systemic vascular resistance and lack of increase in stroke volume and cardiac output after the initiation of CSE analgesia were directly correlated with post-analgesia foetal heart rate decelerations .

Low-dose epidural solutions

Historically, 0.2–0.25% bupivacaine was used to maintain epidural analgesia. In the past several decades, short-acting lipophilic opioids such as fentanyl and sufentanil have been combined with the local anaesthetic. The opioid and local anaesthetic work synergistically, allowing the use of lower concentrations of local anaesthetic (bupivacaine 0.0625%–0.125% or equipotent concentrations of ropivacaine), thus reducing the incidence of local anaesthetic adverse effects such as motor blockade and maternal hypotension without compromising analgesic effectiveness. In the multi-centre Comparative Obstetric Mobile Epidural Trial, a traditional epidural technique using 0.25% bupivacaine was compared with two low-dose techniques (initiation of analgesia with CSE or low-dose bupivacaine-fentanyl epidural analgesia and maintenance of epidural analgesia with 0.1% bupivacaine and fentanyl 2 μg/mL); the use of a low-dose maintenance infusion led to higher spontaneous vaginal delivery rates and corresponding lower instrumental delivery dates . In a systematic review and meta-analysis of randomized trials comparing high-concentration solutions (>0.1% bupivacaine or 0.17% ropivacaine) with low-concentration solutions, the odds of instrumental vaginal delivery was lower in the low-concentration groups (OR 0.70, 95% CI 0.56–0.86) . Thus, the routine use of traditional concentrated solutions of local anaesthetic solutions can no longer be justified.

Bupivacaine is a commonly used local anaesthetic for the maintenance of epidural analgesia, frequently in combination with fentanyl or sufentanil. Levobupivacaine, the S-enantiomer of bupivacaine, is less cardiotoxic than bupivacaine; however, this purported advantage may not be clinically relevant because low concentrations are typically used for modern epidural labour analgesia.

Ropivacaine, another popular local anaesthetic, is a long-acting amide. Ropivacaine is formulated as the single S-enantiomer rather than a racemic mixture; thus, the potential for cardiac toxicity may be lower than bupivacaine. Previous studies have shown ropivacaine to be comparable with bupivacaine in causing sensory blockade with limited placental transfer . It may have a lower propensity for motor blockade relative to equipotent bupivacaine doses required for sensory blockade . A 2015 systematic review found that bupivacaine and ropivacaine have indistinguishable analgesic efficacy and safety profiles and similar maternal satisfaction . Ropivacaine was associated with a lower incidence of motor blockade despite a more prolonged second stage of labour compared with bupivacaine.

The lipid-soluble opioids fentanyl and sufentanil are commonly added to local anaesthetic solutions for the initiation and maintenance of neuraxial labour analgesia. When used appropriately, epidural fentanyl (2–3 μg/mL) and epidural sufentanil (0.2–0.4 μg/mL) have been found to be safe and effective for both the mother and foetus .

Patient-controlled epidural analgesia

Patient-controlled epidural analgesia (PCEA) was first described by Gambling et al. for labour pain control in 1988 . This technique provides flexibility by allowing the parturient to customize analgesia while accommodating escalating analgesic requirements as labour progresses or if pain is increased with oxytocin augmentation of labour. Initially, the technique consisted of patient-initiated boluses only, but currently, a more common technique consists of a continuous background infusion supplemented by patient-controlled bolus doses. The use of PCEA has been shown to reduce local anaesthetic consumption without compromising the quality of analgesia, resulting in fewer side effects and greater maternal satisfaction . A meta-analysis by Van der Vyver et al. found that PCEA was associated with lower local anaesthetic consumption, less motor blockade and lower incidence of breakthrough pain compared with continuous infusion analgesia . In a review, D’Angelo suggested that PCEA reduces local anaesthetic consumption, pain scores and clinician workload and is associated with less motor blockade, resulting in increasing maternal satisfaction compared with continuous infusion techniques .

A typical PCEA regimen includes a background infusion of 5–8 mL/h of dilute local anaesthetic-opioid solution, a patient-controlled bolus dose of 5–10 mL and a lock-out interval of 10–20 min . Halpern and Carvalho suggested that the administration of approximately one-third of the total hourly dose through a continuous background infusion may minimize the risk of breakthrough pain while optimising dose titration . The American Society of Anesthesiologists Practice Guidelines for Obstetric Anesthesia also suggests that a background infusion provides better analgesia than a pure bolus technique .

The basal or background infusion rates used in clinical practice are quite varied. Most studies recommend a moderate basal infusion rate (4–6 mL/h) with the aim of reducing pain scores and the incidence of breakthrough pain without increasing the risk of adverse effects or local anaesthetic consumption . Loubert et al. compared seven studies with ‘low-rate’ basal infusion (≤4 mL/h) to seven studies with ‘high-rate’ basal infusion (≥5 mL/h) and suggested that high-rate basal infusion may be more effective than low-rate infusions . In a 2015 systematic review, the addition of a basal infusion was found to increase the risk of instrumental delivery and prolong the second stage of labour, however, with a reduced need for physician-administered rescue boluses .

Programmed intermittent epidural boluses

The program intermittent epidural bolus (PIEB) technique uses a programmed infusion pump to administer intermittent boluses of epidural solution to maintain analgesia, rather than a continuous infusion. The rationale behind automated mandatory boluses (AMBs) or the PIEB technique is that delivering the basal local anaesthetic solution as regularly spaced, intermittent boluses may provide improved analgesia with a lower drug dose compared with continuous infusions. The concept is similar to the improved analgesia observed with a pure PCEA (no background infusion) technique compared with a continuous infusion. It is hypothesized that drug solution is more widely distributed in the epidural space when administered as a bolus and under greater pressure, rather than as a continuous infusion. An epidural catheter for labour analgesia is commonly placed in the mid-lumbar epidural space, but distribution to the low thoracic and sacral epidural spaces is necessary for complete analgesia. In an in vitro model, bolus injection through a multi-orifice epidural catheter resulted in the exit of the solution from all holes of the multi-orifice catheter, whereas the solution only exited the proximal orifice during a continuous infusion . Similarly, a human cadaver study also suggested that bolus administration produces more uniform spread of solution in the epidural space .

Multiple studies have found improved analgesia when the basal dose is administered as a bolus rather than a continuous infusion. Fettes et al. found that the use of regular intermittent epidural injections (without PCEA) was associated with a lower requirement for epidural rescue medication, less drug use and a longer time to first rescue bolus while providing equivalent pain relief compared with a continuous infusion . Similarly, Chua and Sia found that parturients who received intermittent epidural boluses had a longer duration of uninterrupted analgesia after the initiation of CSE analgesia, lower pain scores and more cephalad extent of sensory block . In a 2016 study, Nunes et al. suggested that intermittent epidural bolus may be associated with lower risk of caesarean delivery than continuous epidural infusion .

The AMB program was incorporated in a single-pump system by Sia et al. who compared a PCEA technique with a basal infusion (5 mL/h) to PCEA with AMB technique (5 mL every 60 min) . The PCEA/AMB group had reduced local anaesthetic consumption, longer analgesia before the first patient-administered bolus and a smaller proportion of parturients who required self-administered boluses. There was, however, no difference in the need for clinician interventions. A follow-up study using a modified version of the original algorithm also demonstrated similar results as did a study by Wong et al. using a dual pump system to administer the intermittent bolus and PCEA .

In another randomized trial that investigated women who received either programmed intermittent boluses of 10 mL/h or a continuous epidural infusion of 10 mL/h (both in conjunction with PCEA), more women who had received a continuous infusion developed earlier and more frequent lower limb motor block (37% vs 2.7%) . Therefore, the incidence of instrumental delivery was 20% in the infusion group and 7% in the intermittent bolus group. Local anaesthetic consumption, additional PCEA requirement and the mean number of PCEA boluses per patient were also lower in the intermittent bolus group despite similar pain scores.

The effects of manipulating the programmed intermittent bolus time interval and injection volume was further investigated by Wong et al. who randomized women to one of three programmed intermittent bolus dose regimens: 2.5 mL every 15 min, 5 mL every 30 min or 10 mL every 60 min . The local anaesthetic consumption was significantly reduced when the time interval between intermittent bolus and bolus volumes were increased.

The AMB lockout period(s), bolus volume(s) and analgesia solutions vary significantly among studies investigating AMB for the maintenance of labour analgesia; the optimal combination is not known. However, despite diverse drug administration parameters, the majority of AMB studies found decreased local anaesthetic consumption, improved maternal satisfaction scores, decreased duration of the second stage of labour and decreased number of clinician rescue boluses in AMB groups compared to continuous infusion groups . This is also demonstrated in an impact study when clinical practice changed from a PCEA to a PIEB technique .

Role of combined spinal epidural technique

The initiation of neuraxial labour analgesia using the combined spinal epidural (CSE) technique has gained popularity in recent years. CSE analgesia was initially introduced to reduce the adverse effects associated with traditional epidural analgesia and to improve maternal mobility. Compared with traditional epidural analgesia, the major advantage of CSE analgesia is the rapid onset of uniform analgesia. CSE analgesia reliably blocks both low thoracic and sacral nerve roots with minimal maternal and umbilical cord blood concentrations of analgesics because of the low doses of local anaesthesia and opioid required to initiate spinal analgesia . The CSE ‘needle-through-needle’ technique may improve the proper placement of a functioning epidural catheter; verification of placement of the spinal needle tip in the subarachnoid space by the return of the cerebrospinal fluid through the needle makes it highly likely that the tip of the epidural needle is correctly sited in the epidural space . The dural puncture may also allow subarachnoid transfer of epidurally administered drugs, potentially enhancing the spread of the block and the analgesic quality .

Despite the widespread use of this technique, CSE analgesia has not been shown to confer advantages compared with epidural analgesia in terms of obstetric or neonatal outcomes . A recent randomized double-blind trial found no differences between CSE and epidural analgesia in neonatal or obstetric outcomes, including foetal heart abnormalities . Interestingly, in a study using non-invasive cardiac output assessment, high baseline systemic vascular resistance and lack of increase in stroke volume and cardiac output after the initiation of CSE analgesia were directly correlated with post-analgesia foetal heart rate decelerations .

Low-dose epidural solutions

Historically, 0.2–0.25% bupivacaine was used to maintain epidural analgesia. In the past several decades, short-acting lipophilic opioids such as fentanyl and sufentanil have been combined with the local anaesthetic. The opioid and local anaesthetic work synergistically, allowing the use of lower concentrations of local anaesthetic (bupivacaine 0.0625%–0.125% or equipotent concentrations of ropivacaine), thus reducing the incidence of local anaesthetic adverse effects such as motor blockade and maternal hypotension without compromising analgesic effectiveness. In the multi-centre Comparative Obstetric Mobile Epidural Trial, a traditional epidural technique using 0.25% bupivacaine was compared with two low-dose techniques (initiation of analgesia with CSE or low-dose bupivacaine-fentanyl epidural analgesia and maintenance of epidural analgesia with 0.1% bupivacaine and fentanyl 2 μg/mL); the use of a low-dose maintenance infusion led to higher spontaneous vaginal delivery rates and corresponding lower instrumental delivery dates . In a systematic review and meta-analysis of randomized trials comparing high-concentration solutions (>0.1% bupivacaine or 0.17% ropivacaine) with low-concentration solutions, the odds of instrumental vaginal delivery was lower in the low-concentration groups (OR 0.70, 95% CI 0.56–0.86) . Thus, the routine use of traditional concentrated solutions of local anaesthetic solutions can no longer be justified.

Bupivacaine is a commonly used local anaesthetic for the maintenance of epidural analgesia, frequently in combination with fentanyl or sufentanil. Levobupivacaine, the S-enantiomer of bupivacaine, is less cardiotoxic than bupivacaine; however, this purported advantage may not be clinically relevant because low concentrations are typically used for modern epidural labour analgesia.

Ropivacaine, another popular local anaesthetic, is a long-acting amide. Ropivacaine is formulated as the single S-enantiomer rather than a racemic mixture; thus, the potential for cardiac toxicity may be lower than bupivacaine. Previous studies have shown ropivacaine to be comparable with bupivacaine in causing sensory blockade with limited placental transfer . It may have a lower propensity for motor blockade relative to equipotent bupivacaine doses required for sensory blockade . A 2015 systematic review found that bupivacaine and ropivacaine have indistinguishable analgesic efficacy and safety profiles and similar maternal satisfaction . Ropivacaine was associated with a lower incidence of motor blockade despite a more prolonged second stage of labour compared with bupivacaine.

The lipid-soluble opioids fentanyl and sufentanil are commonly added to local anaesthetic solutions for the initiation and maintenance of neuraxial labour analgesia. When used appropriately, epidural fentanyl (2–3 μg/mL) and epidural sufentanil (0.2–0.4 μg/mL) have been found to be safe and effective for both the mother and foetus .

Patient-controlled epidural analgesia

Patient-controlled epidural analgesia (PCEA) was first described by Gambling et al. for labour pain control in 1988 . This technique provides flexibility by allowing the parturient to customize analgesia while accommodating escalating analgesic requirements as labour progresses or if pain is increased with oxytocin augmentation of labour. Initially, the technique consisted of patient-initiated boluses only, but currently, a more common technique consists of a continuous background infusion supplemented by patient-controlled bolus doses. The use of PCEA has been shown to reduce local anaesthetic consumption without compromising the quality of analgesia, resulting in fewer side effects and greater maternal satisfaction . A meta-analysis by Van der Vyver et al. found that PCEA was associated with lower local anaesthetic consumption, less motor blockade and lower incidence of breakthrough pain compared with continuous infusion analgesia . In a review, D’Angelo suggested that PCEA reduces local anaesthetic consumption, pain scores and clinician workload and is associated with less motor blockade, resulting in increasing maternal satisfaction compared with continuous infusion techniques .

A typical PCEA regimen includes a background infusion of 5–8 mL/h of dilute local anaesthetic-opioid solution, a patient-controlled bolus dose of 5–10 mL and a lock-out interval of 10–20 min . Halpern and Carvalho suggested that the administration of approximately one-third of the total hourly dose through a continuous background infusion may minimize the risk of breakthrough pain while optimising dose titration . The American Society of Anesthesiologists Practice Guidelines for Obstetric Anesthesia also suggests that a background infusion provides better analgesia than a pure bolus technique .

The basal or background infusion rates used in clinical practice are quite varied. Most studies recommend a moderate basal infusion rate (4–6 mL/h) with the aim of reducing pain scores and the incidence of breakthrough pain without increasing the risk of adverse effects or local anaesthetic consumption . Loubert et al. compared seven studies with ‘low-rate’ basal infusion (≤4 mL/h) to seven studies with ‘high-rate’ basal infusion (≥5 mL/h) and suggested that high-rate basal infusion may be more effective than low-rate infusions . In a 2015 systematic review, the addition of a basal infusion was found to increase the risk of instrumental delivery and prolong the second stage of labour, however, with a reduced need for physician-administered rescue boluses .

Programmed intermittent epidural boluses

The program intermittent epidural bolus (PIEB) technique uses a programmed infusion pump to administer intermittent boluses of epidural solution to maintain analgesia, rather than a continuous infusion. The rationale behind automated mandatory boluses (AMBs) or the PIEB technique is that delivering the basal local anaesthetic solution as regularly spaced, intermittent boluses may provide improved analgesia with a lower drug dose compared with continuous infusions. The concept is similar to the improved analgesia observed with a pure PCEA (no background infusion) technique compared with a continuous infusion. It is hypothesized that drug solution is more widely distributed in the epidural space when administered as a bolus and under greater pressure, rather than as a continuous infusion. An epidural catheter for labour analgesia is commonly placed in the mid-lumbar epidural space, but distribution to the low thoracic and sacral epidural spaces is necessary for complete analgesia. In an in vitro model, bolus injection through a multi-orifice epidural catheter resulted in the exit of the solution from all holes of the multi-orifice catheter, whereas the solution only exited the proximal orifice during a continuous infusion . Similarly, a human cadaver study also suggested that bolus administration produces more uniform spread of solution in the epidural space .

Multiple studies have found improved analgesia when the basal dose is administered as a bolus rather than a continuous infusion. Fettes et al. found that the use of regular intermittent epidural injections (without PCEA) was associated with a lower requirement for epidural rescue medication, less drug use and a longer time to first rescue bolus while providing equivalent pain relief compared with a continuous infusion . Similarly, Chua and Sia found that parturients who received intermittent epidural boluses had a longer duration of uninterrupted analgesia after the initiation of CSE analgesia, lower pain scores and more cephalad extent of sensory block . In a 2016 study, Nunes et al. suggested that intermittent epidural bolus may be associated with lower risk of caesarean delivery than continuous epidural infusion .

The AMB program was incorporated in a single-pump system by Sia et al. who compared a PCEA technique with a basal infusion (5 mL/h) to PCEA with AMB technique (5 mL every 60 min) . The PCEA/AMB group had reduced local anaesthetic consumption, longer analgesia before the first patient-administered bolus and a smaller proportion of parturients who required self-administered boluses. There was, however, no difference in the need for clinician interventions. A follow-up study using a modified version of the original algorithm also demonstrated similar results as did a study by Wong et al. using a dual pump system to administer the intermittent bolus and PCEA .

In another randomized trial that investigated women who received either programmed intermittent boluses of 10 mL/h or a continuous epidural infusion of 10 mL/h (both in conjunction with PCEA), more women who had received a continuous infusion developed earlier and more frequent lower limb motor block (37% vs 2.7%) . Therefore, the incidence of instrumental delivery was 20% in the infusion group and 7% in the intermittent bolus group. Local anaesthetic consumption, additional PCEA requirement and the mean number of PCEA boluses per patient were also lower in the intermittent bolus group despite similar pain scores.

The effects of manipulating the programmed intermittent bolus time interval and injection volume was further investigated by Wong et al. who randomized women to one of three programmed intermittent bolus dose regimens: 2.5 mL every 15 min, 5 mL every 30 min or 10 mL every 60 min . The local anaesthetic consumption was significantly reduced when the time interval between intermittent bolus and bolus volumes were increased.

The AMB lockout period(s), bolus volume(s) and analgesia solutions vary significantly among studies investigating AMB for the maintenance of labour analgesia; the optimal combination is not known. However, despite diverse drug administration parameters, the majority of AMB studies found decreased local anaesthetic consumption, improved maternal satisfaction scores, decreased duration of the second stage of labour and decreased number of clinician rescue boluses in AMB groups compared to continuous infusion groups . This is also demonstrated in an impact study when clinical practice changed from a PCEA to a PIEB technique .