Childbirth has been described as an extremely painful physical activity, with women experiencing the highest pain scores on the medical pain scale, and the birth of modern anesthesiology in the early 19th century opened up the possibility of pain-free childbirth for women. in 1848, British obstetrician Dr. Simpson used chloroform to provide pain relief for a woman giving birth in Edinburgh. In 1848, British obstetrician Simpson used chloroform to successfully administer labor analgesia to a woman in Edinburgh. With the advancement of science and technology, today's labor analgesia techniques have been better developed. Around the world, local analgesia is used for labor analgesia, with intrathecal labor analgesia being the most widely used. The choice of anesthetics is also more diverse, including local anesthetics such as ropivacaine and bupivacaine, which are good for blocking the upward movement of sensory fibers, and opioids such as fentanyl and sufentanil, which are good for promoting the release of opioids from the nervous system. A review of proven labor analgesia modalities and commonly used analgesic medications that are commonly used within today's medicine is presented.
1 Analgesic drugs commonly used in childbirth
Analgesic drugs for labor and delivery are generally required to be able to block sensory fibers, slow down pain sensation or enhance the body's endogenous analgesia, while not affecting motor fibers, so that the mother can move freely and actively cooperate with the labor and delivery. Labor analgesics should be administered in such a way as to avoid any harm to the mother or the newborn and to stimulate the health of the mother and the newborn. Considering that women in labor are a high-risk group, special attention should be paid to the type of anesthetic or analgesic to be used, the dosage, and so on.
1.1 Amides
1.1.1 Bupivacaine
Bupivacaine, a commonly used anesthetic in modern clinical medicine, is a long-acting amide local anesthetic with the molecular formula C₁₈H₂₈N₂ O. It is generally a racemic compound consisting of 50:50 R-type and S-type mirror images. The physical manifestation is a white crystalline substance. Its physical manifestation is a white crystalline powder, odorless and bitter in taste. Bupivacaine anesthesia lasts 2-3 times longer than lidocaine, has less effect on circulation and respiration, and is not irritating to tissues.
The mechanism of action of bupivacaine is to bind to the receptor on the nerve membrane, blocking the sodium channel, so that the nerve membrane potential can not reach the action potential queue value, can not turn on the depolarization, so that the nerve impulse can not be transmitted. Bupivacaine acts in epidural blockade onset of action time is about 16~18 minutes, lasting 200~400 minutes, peak plasma concentration is 0.88 μg/mL, plasma protein binding rate is about 84%~95%. Drug metabolism is metabolized by the liver, and the decomposition products and the original drug are excreted by the kidneys.
Bupivacaine is used for epidural block at concentrations of approximately 0.25% to 0.75%, 0.75% concentration is contraindicated in obstetrics, and only 0.125% concentration is required for postoperative analgesia. For subarachnoid block the concentration is about 0.5%~0.75%, the dosage is according to the need. It should be used with caution in patients with low plasma protein, hepatic and renal hypoplasia, acidosis, hypoxia, and in women who are at high risk for maternal death. The mother herself is a high-risk group should also be used with caution.
1.1.2 Ropivacaine
Ropivacaine (ropivacaine) is also an amide local anesthetic, with the molecular formula C₁₇ H₂₆ N₂ O. It is a pure levorotatory isomer, which has a lower toxicity and longer duration of action than the dextrorotatory isomer. Ropivacaine is less fat-soluble, and low-dose ropivacaine has a better sensory-motor separation effect due to its slower arrival at motor nerve fibers but better sensory nerve block than bupivacaine The use of ropivacaine in labor analgesia can lead to better sensory-motor separation. Its use in labor analgesia allows women to maintain normal activities while relieving pain.
Ropivacaine produces sensorimotor dissociation and is commonly used for epidural labor analgesia due to its high penetration, rapid dispersion, and wide distribution after entering the bloodstream. However, the analgesic effect of low concentration of ropivacaine alone is poor, and it is generally adopted to prolong the analgesic time by means of the combined use of sufentanil or dexmedetomidine in the epidural.
1.2 Opioids
Studies on the mechanism of spinal opioid analgesia have revealed that pregnancy and labor pain are related to endogenous spinal opioid peptides, and that the level of happy hormones in laboring mothers activates the spinal endorphin/delta receptor and prednisolone/κ receptor analgesic systems, which results in significant analgesic effects and reduces the amount of medication used for obstetric analgesia.
1.2.1 Fentanyl
Fentanyl (fentanil) is a potent opioid analgesic with the molecular formula C₂₂ H₂₈ N₂ O light brown solid. It is suitable for all kinds of pain and analgesia in surgery, gynecology and other postoperative and surgical processes, and can also be used as an anesthetic adjuvant in combination with anesthetics.
Fentanyl is an opioid agonist that acts on spinal cord receptors to increase the analgesic effect of opioid peptides on the nervous system and achieve analgesia. Fentanyl belongs to the strong narcotic analgesic, the analgesic effect is 100 times stronger than morphine, the analgesic effect is produced quickly but the duration is shorter. A single intramuscular injection of 0.1 mg, 7-15 minutes to take effect, maintained for 1-2 hours. Fentanyl is weakly addictive and should be used with caution and strict dosage control. Contraindicated in non-opioid analgesics effective people, careful use in intracranial tumors, traumatic brain injury, hepatic and renal insufficiency, underage patients or less than 50 kg weight people.
1.2.2 Sufentanil
Sufentanil (sufentanil) is a new type of potent opioid analgesic with the molecular formula C₂₂H₃₀ N₂ S₂O. Sufentanil's analgesic effect is 5-10 times higher than that of fentanyl, and it is suitable for cardiovascular and neurosurgery as well as obstetrics surgery and postoperative analgesia. Sufentanil has a high binding rate to plasma proteins, especially to α-acid glycoprotein, which is 83%, much higher than that of fentanyl, so that fentanyl has a higher lipophilicity than fentanyl, but its distribution volume is lower than that of fentanyl, and it is retained in the plasma in a higher amount.
Similar to fentanyl, sufentanil acts in the nervous system and binds to μ receptors to produce analgesia. Sufentanil has additional advantages over equivalent doses of fentanyl. Sufentanil has a faster onset of action than fentanyl and is less severe in blocking motor fibers, and its use during labor is less likely to impede maternal movement. When used as an analgesic component of combined anesthesia, sufentanil is administered in adult patients at doses of approximately 0.5-5.0 μg/kg; as a stand-alone anesthetic for intravenous induction, it is not commonly used during labor and delivery, and is administered at doses of approximately 8-30 μg/kg.
1.2.3 Remifentanil
Remifentanil is a new generation of fast-acting, ultra-short-acting narcotic analgesic, with the molecular formula of C₂₀H₂₈ N₂₅ O, which is a μ-opioid receptor agonist. The analgesic effect of remifentanil is dose-dependent, has a capping effect, does not harm the liver and kidney function, and wakes up quickly after anesthesia. And because it is easily hydrolyzed by lipase in the body, it has a fast onset of action, short duration of action, and there is no opioid accumulation after continuous administration.
The mechanism of action of remifentanil is similar to that of other opioids. When remifentanil is used for anesthesia in cesarean section, it is general anesthesia, with an induction dose of 0.5 μg/kg, which is infused at a rate of 0.2 μg/(kg-min), and used in combination with propofol, it can effectively reduce the maternal stress response. It is worth noting that when remifentanil is used for obstetric analgesia, in addition to its role in assisting epidural blockade, unlike local anesthetic or other opioids, it is administered intravenously for analgesia, and clinical trials have shown that this is the most significant way in which remifentanil works. Remifentanil due to strong analgesic effect and has a unique non-specific lipase metabolism, patients with hepatic and renal impairment are not allowed to adjust the dose according to the needs of surgery, depth of anesthesia. The dose of remifentanil should not be adjusted in patients with hepatic or renal impairment according to surgical needs and depth of anesthesia.
1.3 Other drugs
1.3.1 Dexmedetomidine
Dexmedetomidine (dexmedetomidine) is a potent α2-adrenergic receptor agonist with the molecular formula C₁₃H₁₆N₂. Dexmedetomidine rapidly diffuses into the cerebrospinal fluid, inhibits the release of norepinephrine from the presynaptic membrane, and at the same time hyperpolarizes the cell membrane, inhibiting the transmission of pain signals and producing a sedative effect that resembles that of a natural sleep and reduces the sensation of pain in labor.
At the same time, dexmedetomidine is fat-soluble and is easily absorbed into the bloodstream by the epidural adipose tissue, producing a central sedative effect and decreasing the stress of the organism. Dexmedetomidine can selectively agonize the body. Dexmedetomidine can selectively agonize the central nervous system and peripheral receptors, reduce parasympathetic nervous tension and the release of catecholamines (stimulated sympathetic secretion by labor pain), and dexmedetomidine can promote peristalsis of the gastrointestinal tract, thus reducing the incidence of nausea and vomiting. The incidence of urinary retention due to suppression of the micturition reflex, urethral relaxation and differential contraction of the urethral muscles is also much lower than with opioids.