Summary Childbirth pain is a perfect example of acute pain as somatic, visceral and related components are present. This kind of pain opens up a wide field of study and wide therapeutic possibilities to the algologist. Epidural analgesia in childbirth still presents some limitations, related both to the possible motor block produced by local anesthetics (LAs); they are able to interfere variously on the course of childbirth, as well as potential maternal-fetal toxic effects induced by the possible passage in circulation of the drugs used. Clinically, the best applicable technique is the segmental peridural and the CSE (combined spinal-epidural anesthesia); the technological improvement essentially translates into a reduction of the side effects.
With LAs, opioids and intrathecal alpha-2-agonists can be associated as adjuvants.
Riassunto Il dolore da travaglio di parto, perfetto esempio di dolore acuto nel quale sono presenti le componenti somatica, viscerale e riferita, apre all'algologo un vasto campo di studio e ampie possibilità terapeutiche. L'analgesia epidurale in travaglio di parto presenta, tuttora, alcune limitazioni correlate sia al possibile blocco motorio prodotto dagli anestetici locali (AL) in grado di interferire variamente sul decorso del parto, sia ai potenziali effetti tossici materno-fetali indotti dall'eventuale passaggio in circolo dei farmaci utilizzati. Dal punto di vista clinico, la tecnica applicabile con i migliori risultati è la peridurale segmentaria e la CSE (anestesia combinata spinale-epidurale); il miglioramento tecnologico si traduce essenzialmente in una riduzione degli effetti collaterali.
Agli AL si possono associare, come adiuvanti, gli oppiacei e gli alfa-2-agonisti intratecali.
Key words Obstetrics, epidural analgesia, CSE-LAs, opioids, intrathecal clonidine
Parole chiave Ostetricia, analgesia epidurale, CSE-AL, oppiacei, clonidina intratecale
Labour pain is one of the best known sources of acute pain. It is an expected pain, prepared and feared during the nine months of gestation. In every century you can find evidence of suffering and mortality related to childbirth. The first attempts to control childbirth pain were psychological: hypnosis techniques were used by the Egyptians, the Chinese and this can also be found in the book of Genesis.1
Pregnancy changes the woman physiologywith a series of adaptations. From the anesthesiological point of view, the most affected apparatuses are the cardiovascular, respiratory and renal systems.2
Childbirth is the process which, through the integration of mechanical and dynamic phenomena, leads to the expulsion of the foetus. The value of childbirth represents a perfect model of acute pain in medicine: in particular, it is the only example of the simultaneous presence of somatic, visceral and related pain.3
Somatic pain is due to compression, dilation and stretching of the structures that are part of the perineum and vulva; it is usually evident in the expulsion period. The perineal area is innervated by sensitive fibers of the pudendum whose roots enter the medullaposterior cords at the level of the sacral segments S2-S4.4
Visceral pain is caused, however, by the dilation of the neck, the contraction of the uterus, the stretching of the appendages, the visceral perineum and, above all, the parietal one. Like all visceral pains, it is often accompanied by an emotional reaction (sense of anguish, of imminent death) and by vegetative symptoms (nausea, vomiting, bradi or tachycardia, dysthymia, pallor, sweating); it also has a deep, vague, inaccurate and poorly demarcable location (Figure 1). It can surface at the level of the abdominal wall in areas that are metamericically connected with the bowel in pain (reported pain); the modalities of parietalization are not yet clarified in all their aspects, the reported pain is therefore the superficialisation or parietalization of visceral pain.5 An explanation of the mechanism of onset of the reported pain is that both the uterus and some structures somatic (e.g. the abdominal wall) divide the same neuronal pool.6,7
Epidural and spinal analgesia are well recognized as forms of pain relief available in women's labour. Traditionally epidural analgesia has been performed for years using bupivacaine, in 1979 a lower dose of 0.125% have been reported to be as effective as the traditional concentration.8,9 Bupivacaine, being very linked to proteins, has the lowest placental (and therefore foetal) release among local anesthetics. The long duration of action provides a good sensory block with moderate muscle block. The side effects are cardio-toxicity and CNS toxicity. Concern about these unfavorable effects has pushed research towards alternative agents. The use of ropivacaine was confirmed able to reduce the motor block compared to bupivacaine especially at low concentration.10-12 Levo-bupivacaine is the levogiro enantiomer of bupivacaine, it was created for clinical use based on reduced cardiac toxicity and CNS; a preliminary comparison suggests that levobupivacaine may produce less motor block if used subarachnoidly but that Apgar scores and umbilical cord pH values are similar.13-15
In the Eighties, spinal and epidural opioids were introduced into clinical practice for analgesia in labour.16-21 The local anesthetic doses used for labor analgesia have decreased dramatically over the past 30 years.
The introduction of new techniques such as combined spino-epidural analgesia (CSE), new drugs such as ropivacaine and levobupivacaine, the widespread practice of adding more drugs with low concentrations of local anesthetic solution have changed the anesthetic practice satisfying the main aim of obstetric analgesia: practicing a spontaneous vaginal birth in pain without or with minimal obstetric intervention.22-26
The maternal analgesia can directly affect the baby with the transfer through the placenta. AL cause a dose-dependent motor block; high concentrations of AL can cause an increased risk of malpresentations,27 can prolong the expulsion period28 with a higher incidence of instrumental delivery.29 Highly concentrated local anesthetic can cause relaxation of the pelvic floor which can interfere with the internal rotation of the fetal head.30,31 The relaxation of the skeletal muscle not only increases the risk of malposition of the fetal head but causes a decrease in the pushing force too. The use of AL plus vasoconstrictors should be advised against in epidural analgesia in labor because epinephrine, presumably for its beta-adrenergic activity, can cause tocolytic effects, with a decrease in the frequency of uterine contractions.32,33
As for opioids beyond the usual controversies related to the method of administration to the dosage and any associations with AL,34,35 they could interfere with the progression of labor or through effects on the spinal centers that control uterine contractility or through a decrease in endogenous secretion of oxytocin.36 Clonidine does not directly interfere with uterine contractile activity, but enhances the action of AL and opioids, both in the epidural and in the spinal.37-39 The use of oxytocin is closely related to regional analgesia.40,41 Since the use of oxytocin is often associated with painful labors, the regional analgesia can be planned prior to administration of oxytocin.42,43 Infusion of fluids prior to regional analgesia may transiently reduce the contractile activity of uterus.44
Rapid expansion of plasma volume can cause a sudden release of atrial natriuretic factor or act directly on uterine vessels causing the release of vasoactive peptides. The natriuretic factor can cause vasodilation, natriuresis and diuresis, inhibiting the secretion or action of angiotensin II and norepinephrine45 and is also a powerful inhibitor of uterine contractility.46
Finally, the mother's position can interfere with uterine activity; the parturient on the left side will have less frequent but more effective contractions. Also allowing the mother to walk during regional analgesia labour reduces the risk of operational birth.47,48
Stage I pain is caused by uterine contractions that cause the cervico-vaginal angle to flatten and the cervix dilate with distension of the perineal plane.49,50 It is also partly due to ischemia of the myometrium of the cervix caused by contractions and vasoconstrictor action caused by sympathetic hyperactivity.51,52
In stage I, in addition to the visceral component, there is a minimal somatic component due to the distension and dilation of the muscles, pelvic ligaments and modulated vagina, as well as from the unmyelinated C fibers, from the A delta, myelinated fibers.53
As you pass through stage II, somatic pain becomes predominant over visceral pain. The presented part of the fetus relaxes the structures of the pelvis and peritoneum. Progression causes stretching of the cutaneous fascia of the vagina and adjacent structures (urethra, bladder, pelvic muscles, peritoneum, uterine ligaments).4
This differentiation of pain in the two stages of labor is fundamental for the pharmacological management of analgesia, as visceral pain is sensitive to opioids, while local anesthetic finds its place in the treatment of somatic pain (Table 1). Selective sequential analgesia is based on a sequential approach that takes into account the characteristics of pain during labor (which has two distinct phases, visceral and somatic) and pharmacological selectivity. The use of spino-epidural combined anesthesia (CSE) puts this concept into practice. In stage I of labour, subarachnoid opioids associated with clonidine are used,54 while in stage II of labor low-concentration local epidural anaesthetics are used. The transition from the first type of treatment to the second must be determined by monitoring the clinical characteristics of pain. The selectivity of the approach concerns the different receptors and nerve fibers involved in the two phases of labour: in the first stage, the blockage of the sodium and potassium channels with opioids and clonidine; and phasic block of the sodium channels in the delta and C fibers with bupivacaine or ropivacaine. The pharmacological selectivity of opioids and clonidine on their receptors allows the synergistic use of the two drugs useful for reducing the dosage of both and minimizing side effects.56
In addition, in the second stage of labour the synergistic action of clonidine and local anesthetics capable of producing a phasic blockage (such as bupivacaine and ropivacaine) allows the use of low concentrations of the latter without changing the motor function and the degree of anesthesia. 15 µ of clonidine associated with 10 µg of sufentanil or fentanyl is used subarachnoidly, while ropivacaine is used for the treatment of somatic pain (0.1% 10 ml epidurally). In conclusion, the advantages of the combined spinal-epidural block during labor are: rapid onset with good analgesia; absence of motor blockage; low drug dosages and reduced fetal absorption; minimal influence on the progression of labor. But the main advantage is the pharmacological modulation carried out with the combined selective sequential analgesia consists in the exploitation of the synergistic action of two drugs, opioid, alpha-2 adrenergic and local anesthetics.
The requirements that make CSE the ideal technique are reported in Table 2.
This guarantees analgesia with ideal characteristics and safety with the possibility of switching to anesthesia when this is required by clinical situations.
A well-conducted CSE analgesia that uses opioid drug combination and an adjuvant clonidine by subarachnoid route, and a low dose of fast-acting AL is effective and safe to obtain an easy and satisfactory pain control throughout the duration of labor and spontaneous vaginal birth, bringing significant benefits to both the mother and the foetus (Table 3) Analgesia with CSE in labour today tends to favor a multi-pharmacological approach such as to allow the use of low concentrations of drugs obtaining effective pain control with minimal side effects. Combining drugs with different mechanisms and sites of action would produce better pain relief with minimal side effects.56
It can be concluded, that epidural or combined spinal-epidural analgesia, for labour of childbirth, can be considered far from the accusation of being able to complicate the progression of the happy event provided if all those factors are scrupulously considered and observed, and sufficiently discussed.
Conflict of interests
L'autore dichiara di aver redatto la review in assenza di conflitto di interessi.
18th June 2020
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14) Harding DP, Callier PA, Hunckle RM et al. Comparison of the cardiotoxic effects of bupuvacaine, levobupivacaine and ropivacaine. An in vitro study in guinea-pig and human cardiac muscle (Abstract) Reg Anesth Pain Med 1998; 23(3) suppl:6.