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Statement on the Use of Adjuvant Medications and Management of Intraoperative Pain During Cesarean Delivery

Developed by: Committee on Obstetric Anesthesia
Original Approval: October 23, 2024

Executive Summary

Executive Summary Introduction

  • American Society of Anesthesiologists Statement on Pain During Cesarean Delivery provided background and guidance in the recognition and treatment of pain during cesarean delivery, which occurs in about 15%.
  • Multiple medication types can be delivered via varied routes to help manage pain during cesarean delivery.
  • This statement provides guidance on the use of adjuvant medications to help manage pain during cesarean delivery. No one technique or adjuvant can guarantee full pain relief.  

Neuraxial adjuvant medication

  • Additional local anesthetics such as lidocaine and chloroprocaine can be administered through an epidural catheter to provide additional analgesia. Consider alkalinization of local anesthetic with bicarbonate to increase effectiveness as well as the addition of epinephrine 5 mcg/ml to increase effectiveness and decrease risk of local anesthetic systemic toxicity.
  • Lipophilic opioids such as fentanyl and sufentanil can be administered through an epidural catheter to improve analgesia.

Intravenous adjuvant medication

  • Short acting opioids such as fentanyl are recommended as first line agents for management of pain during cesarean delivery.
  • Ketamine is considered a second line agent for pain that can provide analgesia at subanesthetic doses with minimal neonatal effects, but maternal side effects such as hallucinations can occur.
  • Dexmedetomidine is another second line agent for pain that can provide analgesia and anxiolysis but can cause maternal bradycardia and hypotension.
  • Maternal anxiety can be treated with anxiolytics such as midazolam, dexmedetomidine, or subanesthetic doses of propofol.

Inhalational adjuvant medication

  • Inhaled nitrous oxide can provide additional maternal analgesia and anxiolysis. The concentration of nitrous oxide should not exceed 75%.
  • Volatile anesthetic gases such as sevoflurane are not recommended without a supraglottic airway or endotracheal tube.

Sedation for cesarean delivery

  • While both moderate and especially deep sedation for cesarean delivery are typically avoided, some circumstances may justify its use. 
  • Consider shared decision making with the patient prior to initiation of sedation.
  • Use lowest effective doses of sedative medications to decrease risk of maternal harm.
  • Sedation is not a substitute for anesthesia in a patient experiencing pain during cesarean delivery.

Decision to convert to general anesthesia

  • Patients may require conversion from neuraxial to general anesthesia despite supplemental adjuvant medications. 

Psychologic effects

  • Significant pain during cesarean delivery has the potential to cause psychological distress and may immediate or longer-term effects.
  • Acknowledge complaints of pain during cesarean delivery and participate in shared decision making regarding to the decision to convert to general anesthesia, if possible.

Follow-up

  • Provide follow-up with post-operative visits in person or telephonic for patients who required conversion to general anesthesia or for significant pain during cesarean delivery. Refer for additional support, if needed.

Quality improvement

  • Consider internal audits of general anesthesia rate for cesarean delivery, use of anesthetic adjunct medications, and adverse events associated with general anesthesia and the use of anesthetic adjunct medications.

Introduction

The American Society of Anesthesiologists Statement on Pain During Cesarean Delivery1 provided background and guidance in the recognition and treatment of pain during cesarean delivery. One of the recommendations covered in that statement was the supplementation of inadequate neuraxial anesthesia with adjuvant medications such as intravenous fentanyl or inhaled nitrous oxide. This current statement expands upon that topic to provide guidance to anesthesia professionals in order to assist in the treatment of pain during cesarean delivery. 

In pharmacology, adjuvant medications are substances added to a primary treatment, such as a leading drug or therapy, to enhance its effects. These supportive agents play a role in potentiating the action of the primary treatment, managing side effects, or extending therapeutic effects. For example, adjuvant medications can be utilized alongside local anesthetics to optimize pain relief, prolong analgesia, and improve patient comfort during procedures. The selection of adjuvant medication is based on pharmacological properties and their ability to enhance the desired effects of the primary anesthesia agents, reflecting a comprehensive strategy in patient management.

There are multiple routes of administration for adjuvant medications. Intrathecal adjuvant medications are strategically employed in addition to intrathecal or epidural local anesthetics to augment their analgesic/anesthetic effects. Intravenous adjuvant medications are administered intravenously to complement the effects of spinal or epidural procedures, aiming to improve pain relief and overall patient comfort. Additionally, nitrous oxide can be an important inhalational adjuvant to neuraxial anesthesia for cesarean delivery.

Historically, use of adjuvant medications were minimized to reduce the chances of placental transfer to the fetus, neonatal depression and need for neonatal resuscitation at birth, maternal aspiration and transfer into breast milk. The emphasis has shifted to the recognition and treatment of pain during cesarean delivery.1 Patients should be believed when they state that they are experiencing pain. Appropriate interventions such as administration of epidural, intravenous, or inhalational systemic anesthetic adjuvant agents should be considered for the management of intraoperative pain and the surgical procedure should be paused if possible to allow the patient’s condition to improve. Subsequent surgical activity should not resume until the patient is comfortable. 

This statement serves to inform practitioners and give recommendations that may help decrease pain during cesarean delivery under neuraxial anesthesia and help identify and guide management to meet individual patient desires and needs. Recognition of risk factors, past medical or non-medical traumatic experiences, patient education, and shared decision making may help improve patient experience and reduce disparities.

Anesthesiologists and other anesthesia professionals would benefit from guidance in the use of adjuvant medication during cesarean delivery. The American Society of Anesthesiologists Committee on Obstetric Anesthesia identified five topics related to the use of adjuvant medication during cesarean delivery.

Recommendations

The following recommendations regarding the use of adjuvant medications during cesarean delivery were developed by the working group and approved by the Committee on Obstetric Anesthesia and are organized into six topics:

  1. Neuraxial adjuvant medication
  2. Intravenous adjuvant medication
  3. Inhalational adjuvant medication
  4. Sedation for cesarean delivery
  5. Decision to convert to general anesthesia
  6. Quality improvement

Table 1. Neuraxial adjuvant medication

Why This Supplementation with neuraxial adjuvant medications is usually the first intervention for inadequate regional anesthesia for cesarean delivery after skin incision if there is an epidural catheter in place.  
Background Neuraxial anesthetic adjuvant medications include additional epidural local anesthetics (e.g. lidocaine, chloroprocaine), lipophilic opioids (e.g. fentanyl, sufentanil), and alpha2-agonists (e.g. clonidine, dexmedetomidine).
Best Practices 
  • Local Anesthetics: Consider additional epidural administration with rapid-onset supplemental local anesthetics, such as lidocaine 2% with epinephrine 1:200,000 (5 mcg/ml) or chloroprocaine 3%, not to exceed recommended doses for systemic toxicity. 
    • Consider alkalinization with sodium bicarbonate 8.4% (1 ml sodium bicarbonate per 10 ml local anesthetic)2 to hasten onset of lidocaine 2% with epinephrine or chloroprocaine 3% 
      • Lidocaine with epinephrine: Mean onset 5.2 min (SD 1.5 min, range 2-8 min) with alkalinization vs. 9.7 min (SD 1.6 min, range 6-12 min) without alkalinization; mean difference 4.5 min (95% CI 3.5-5.5 min; p < 0.001)3 
      • Chloroprocaine: mean (+/- SD) onset 2.7 +/- 0.8 min with alkalinization vs. 4.2 +/- 0.8 min without alkalinization4
    • Epidural chloroprocaine can be used concurrently with epidural morphine 
      • Eisenach et al. reported that epidural chloroprocaine interfered with the duration of action of epidural morphine5
      • A recent randomized controlled trial demonstrated non-inferiority in 24-hour postoperative opioid consumption between subjects who received epidural morphine 3 mg following loading of the epidural catheter with lidocaine or chloroprocaine6

 

  • Lipophilic opioids (e.g. fentanyl 50-100 mcg, sufentanil 10-20 mcg) are among the most commonly used neuraxial methods to treat pain.
    • At equipotent doses, no differences in onset time, quality of analgesia, or duration of analgesia have been observed between fentanyl and sufentanil.7,8
    • Side effects of epidural lipophilic opioids include systemic absorption, sedation, respiratory depression, nausea/vomiting, and pruritis.7-11
    • No difference in APGAR scores or cord blood pH has been noted with the administration of epidural lipophilic opioids prior to delivery.9-11
  • alpha-2 adrenergic agonists like neuraxial clonidine (75-200 mcg)2, 12-15 or dexmedetomidine (0.5-1 mcg/kg)15-17 have also been used.
    • Side effects of epidural administration of a2 adrenergic agonists include hypotension, decreased heart rate, sedation, and prolonged motor blockade.12-17 
    • No difference in APGAR scores has been noted with the administration of epidural a2-agonists before delivery.14,16
  • Note that many of these commonly used medications do not have specific FDA approved indications for the neuraxial route of administration. The decision to use or not use these modalities is the individual’s decision based on the surgical, maternal, fetal considerations, judgement on patient responsiveness to these and other modalities, and other considerations around management of alternative anesthetic options including general anesthesia (e.g., airway examination, course of labor, etc.). 

Table 2. Intravenous adjuvant medication

Why This  Maternal discomfort during cesarean delivery under neuraxial anesthesia is common. Administration of systemic adjuvant medications can mitigate the sequelae of inadequate neuraxial anesthesia, help relieve discomfort, pain and anxiety and potentially avoid the necessity of conversion to general anesthesia. 
Background The incidence of maternal pain and/or distress during cesarean delivery under neuraxial anesthesia ranges from 11.5% to 22.7%.18-20 Inadequate anesthesia can both adversely impact the intraoperative experience and contribute to long-term consequences, including postpartum depression, post-traumatic stress disorder, and chronic pain.21,22 In addition, pain under neuraxial anesthesia is the leading cause of litigation against anesthesiologists participating in cesarean deliveries.23-25 Supplementation with intravenous medications can potentially alleviate the pain and distress accompanying inadequate neuraxial anesthesia. 
Best Practices 
  • Acknowledge the patient’s experience when they report pain and/or distress. 
    • A recent study highlighted providers’ inaccuracy in identifying discomfort during cesarean delivery, with a reported false negative pain perception rate of 82.6% for obstetricians and 52.2% for anesthesiologists.18 The patient’s stated experience should supersede the anesthesiologist’s or surgeon’s assessment of the surgical block. Dismissal and/or delayed management of a patient’s discomfort can lead to psychological trauma with long-term sequelae.
  • Evaluate the patient’s characterization of discomfort in the context of the clinical scenario
    • Management will depend on the contribution of pain versus anxiety. The appropriate systemic adjuvant medication(s) is/are contingent on the patient’s comorbidities, fetal status, and surgical stage of cesarean delivery. 
  • Solicit and support the patient’s preferences when deciding to administer intravenous adjuvant medications. 
    • Most patients have insight into their analgesic and anxiolytic needs.26,27 Management should be patient-centered, guided by an understanding of the patient’s individual preference for relief versus avoidance of maternal and fetal side effects. 
    • The patient should be informed of potential maternal and neonatal side effects of commonly administered systemic adjuvant medications. 

 

  • Manage pain with analgesic medications.
    • Short-acting opioids are recommended for the first-line management of pain during cesarean delivery.28 The efficacy of systemic opioid analgesia and incidence of maternal side effects (sedation, nausea, pruritis, and respiratory depression) are largely dose-, rather than drug-dependent. All opioids cross the placenta and are associated with a risk of neonatal respiratory depression and neurobehavioral changes.29 The most appropriate opioids for analgesia during cesarean delivery have a quick onset and short duration of action.
      • Remifentanil (20 mcg boluses or 0.05 - 0.1 mcg/kg/min infusion)29-31
      • Alfentanil (250 to 500 mcg boluses, maximum cumulative dose < 10 mcg/kg prior to delivery of the fetus)29 
      • Fentanyl (25 to 50 mcg boluses, maximum cumulative dose < 1.5 mcg/kg prior to delivery of the fetus)29,33
    • Ketamine (10 mg boluses, maximum cumulative dose < 1 mg/kg) is a second-line agent that provides analgesia at subanesthetic doses with no impact on neonatal outcomes (Apgar scores, umbilical blood pH, or need for resuscitation).29,34,35 Consideration should be given to maternal side effects including drowsiness, restlessness, hallucinations, diplopia, and nystagmus.
    • Dexmedetomidine (10 mcg boluses, 0.5 mcg/kg loading dose over 10 minutes, and/or 0.5 – 1 mcg/kg/hr infusion) is a second-line medication that provides both maternal analgesia and anxiolysis with no reported effect on neonatal Apgar scores or umbilical blood pH.36,37 The antisympathetic effects of dexmedetomidine can lead to maternal bradycardia and hypotension. While dexmedetomidine’s distribution half-life is 6 minutes, the terminal elimination half-life is 2 hours.
  • Treat anxiety and psychological distress with anxiolytic medications.
    • Midazolam (0.01 – 0.02 mg/kg) provides anxiolysis without impacting maternal memory formation or neonatal outcomes (Apgar score, neurobehavioral scores, and continuous oxygen saturation).33,38,39
    • Dexmedetomidine (10 mcg boluses, 0.5 mcg/kg loading dose over 10 minutes, and/or 0.5 – 1 mcg/kg/hr infusion) provides both analgesia and anxiolysis with minimal respiratory depression.36-38
    • Propofol infusion (25-50 mcg/kg/min) may provide anxiolysis; respiratory monitoring (EtCO2) required. Patient should be able to converse, thus avoiding deep sedation.

Table 3. Inhalational adjuvant medication

Why This Inhalational systemic adjuvant agents such as nitrous oxide can be used as part of a multimodal approach to treat inadequate analgesia during cesarean delivery. 
Background  Nitrous oxide has been used in labor to provide analgesia and anxiolysis.40 Similarly, nitrous oxide can also be used during cesarean delivery to treat anxiety and pain.41 
Best Practices 
  • Solicit and support the patient’s preferences when deciding to administer inhalational adjuvant medications. 
  • Nitrous oxide
    • Two prospective, double-blind trials found that anxiety VAS scores were lower during cesarean delivery in patients who received a 50% N2O: 50% O2 mixture compared to those who received oxygen alone.41,42
    • The analgesic effectiveness of nitrous oxide is comparatively lower than that of neuraxial and intravenous analgesics.40,43 Anxiolysis is the primary benefit of inhalation N2O use, and should not replace analgesics for the treatment of moderate to severe pain.
    • Inhaled 50% N2O with oxygen is generally safe for both the mother and newborn.
      • An inhaled concentration of 50% N2O with oxygen is routinely utilized and has been shown to significantly reduce anxiety and pain during labor and cesarean delivery without compromising the airway or hemodynamics.40-42 Additionally, it has been shown to have a good safety profile for procedures performed in the emergency department.44
      • N2O should not be administered in concentrations exceeding 70–75% to ensure adequate oxygen delivery.43,44
      • A French prospective survey study of 35,000 pediatric and adult patients who were administered a 50% N2O/O2 mixture as the sole agent for managing procedural pain found that serious adverse effects such as altered consciousness and hypoxia only occurred in 0.03% of patients.45 In the same study, the most common reported adverse effects were agitation, euphoria, nausea and emesis. 
  • Sevoflurane
    • The use of sevoflurane during cesarean delivery is usually restricted to general anesthesia in patients who have an endotracheal tube46 or a supraglottic airway.47
    • In a retrospective study of 1867 patients who had cesarean deliveries in a community hospital, two patients were reported to have received sevoflurane by mask without an endotracheal tube or supraglottic airway.48 The safety of administering sevoflurane as a systemic adjuvant agent to treat inadequate regional anesthesia during cesarean delivery is unknown and its use is not recommended.

Table 4. Sedation for cesarean delivery

Why This  Patients with pre-existing anxiety may benefit from administration of anxiolytic medications to improve their experience. Additionally, judicious use of moderate sedation may allow the patient to avoid conversion to general anesthesia in select circumstances. 
Background  Providing moderate or deep sedation during surgical procedures performed with regional anesthesia is common in non-pregnant patients to improve comfort, allay anxiety, and produce amnesia.49 During cesarean delivery, doses of sedative-hypnotic medications are typically limited or avoided due to the maternal risks of pulmonary aspiration, respiratory depression, hypoxemia, and amnesia of the birth experience and the neonatal risks of central nervous system and/or respiratory depression and increased need for neonatal resuscitation.2 An analysis of 4,305 deliveries at one tertiary center in Israel between 2017 – 2020 found that 9.1% of patients required anxiolysis50 and a retrospective study of 1867 patients who had cesarean deliveries at a community hospital reported that 32 (1.7%) and 148 (7.9%) patients received intravenous midazolam and propofol, respectively.48  
Best Practices 
  • Discuss the plan to administer intravenous sedative medications with the patient beforehand. 
    • Discussing the plan, including the risks and benefits, facilitates tailored treatment that accounts for patients’ preferences and values through shared decision-making.51
  • Titrate medications incrementally to the lowest required doses to produce desired degree of anxiolysis. 
    • The American Society of Anesthesiologists Statement on Continuum of Depth of Sedation: Definition of General Anesthesia and Levels of Sedation/Analgesia52 provides the following definitions of sedation levels:
      • Minimal sedation/anxiolysis, whereby the patient has ‘normal response to verbal stimulation’ , with respiratory and cardiovascular functions not affected is ideal. 
      • Patients with significant psychological distress and discomfort may benefit from moderate sedation/analgesia (‘Conscious Sedation’) to cope with intraoperative anxiety and discomfort, the features of which include ‘purposeful response to verbal commands, either alone or accompanied by light tactile stimulation,’ with protective airway reflexes and ventilation intact. Unwanted side effects from agents such as ketamine, include hallucination, dysphoria and uncontrolled movements may occur.53 
      • Deep sedation, where ‘patients cannot be easily aroused but respond purposefully following repeated or painful stimulation,’ may have loss of protective airway reflexes, and support required to ensure airway patency and adequate ventilation risks pulmonary aspiration of gastric contents should be avoided. 
    • Note that sedation is a continuum, and an individual patient’s response may not be predictable. Personnel providing sedation should be able and prepared to rescue patients whose level of sedation becomes deeper than initially intended. Stop administering agents should the degree of sedation become excessive. 
    • Concern about impaired memory formation during childbirth associated with midazolam in doses from 2 – 7 mg IV has existed since the agent was introduced into practice in the 1980s.54 Frolich et al. found no difference in the ability to recall delivery for women randomized to receive fentanyl 1 mcg/kg and midazolam 0.02 mg/kg immediately prior to spinal anesthesia compared to the control group receiving saline.33 There were also no differences in neonatal Apgar or neurobehavioral scores or pulse oximetry for 3 hours. 

 

  • Sedation is not a treatment for pain and is not a substitute for general anesthesia. Sedation should be used with caution. Consider inducing general anesthesia and securing the airway with an endotracheal tube for patients with significant intraoperative pain or discomfort. 

 

  • In patients receiving moderate sedation, provide supplemental oxygen to avoid hypoxemia and monitor exhaled carbon dioxide.
    • Inadequate ventilation is tolerated poorly in late pregnancy, with rapid oxygen desaturation during periods of apnea, due to lower functional residual capacity and higher oxygen consumption.55
    • Generally, try to avoid moderate sedation in both fasted and non-fasted patients and patients in labor, due to the risk of pulmonary aspiration. 

 

  • Risks and benefits of providing moderate sedation to both patients who are fasted undergoing elective obstetric procedures and to patients who are not fasted undergoing non-elective obstetric procedures should be carefully considered.
    • Lower esophageal sphincter tone is reduced during pregnancy with the incidence of gastroesophageal reflux disease exceeding 50% in the third trimester.56 Laboring patients have significantly reduced gastric emptying.57 Both factors may increase the risk of pulmonary aspiration of gastric contents with sedation. 
    • Consider timely pre-procedural administration of pharmacologic gastrointestinal prophylaxis.58
    • Contemporary assessments suggest that the actual risk of aspiration is very low. A retrospective chart review of patients who underwent cesarean delivery with neuraxial anesthesia at two hospitals in Israel from 2007 – 2018 identified only one incident of aspiration among approximately 26,000 patients; in that patient, deep sedation had been performed with midazolam, ketamine and fentanyl while undergoing emergent cesarean delivery under spinal anesthesia for chorioamnionitis.59 In this same Israeli cohort, the incidence of aspiration for patients undergoing cesarean delivery with general anesthesia was 2 in 22,690, in the setting of difficult laryngoscopy in non-fasted patients undergoing emergent delivery, without gastrointestinal prophylaxis.
  • Allow for breastfeeding
    • Breastfeeding may take place after sedation and anesthesia, once the patient is alert enough to do so.60
    • Most medications do not cross into the breastmilk in a clinically significant amount to affect the newborn; the correct scientific measure is relative infant dose (RID), with <10% of maternal considered acceptable.

Table 5. Decision to convert to general anesthesia

Why This  Conversion to general anesthesia should be considered when surgical pain under neuraxial anesthesia for cesarean delivery is refractory to systemic anesthetic adjuvant medications. 
Background Hawkins et al reported a 17-fold increase in mortality among patients who had general anesthesia for cesarean delivery compared to patients who had regional anesthesia.61 This finding prompted a change in practice to lower the rate of general anesthesia for cesarean delivery and one institution reported a rate of less than one percent.62 Inadequate anesthesia for cesarean delivery can cause significant psychological trauma for the patient.63 Expert definitions of neuraxial block failure differ64,65 but the patient’s experience of pain is the foremost consideration.66 
Best Practices 
  • Acknowledge complaints of pain
    • Complaints of pain expressed by the patient must be believed by the anesthesia professional67
  • Determine whether anxiolysis, analgesia, or both are indicated
    • Neuraxial, intravenous, and inhalational analgesia addressed in Tables 1, 2, and 3, respectively
    • Anxiolysis addressed in Table 4
  • Balance patient autonomy and beneficence
    • Patients with inadequate analgesia during cesarean delivery are in a vulnerable position and it is sometimes difficult to determine how much decision making the patient is able to perform or wants to perform.68
    • Facilitate a patient request for conversion to general anesthesia if feasible.
  • General anesthesia should be avoided when possible but initiated when indicated
    • Potentially avoidable general anesthesia for cesarean delivery has been associated with adverse events.69
    • General anesthesia for cesarean delivery has become safer with advances in technology and human factors and should be initiated when indicated.70
  • Provide follow up with postoperative visits to the bedside and/or phone calls67

Table 6. Quality improvement

Why This  Quality improvement measures enable individuals and institutions to optimize their anesthetic practice. 
Background Anesthesiologists are integral to the safe provision of modern obstetric care, delivery of anesthesia, and perioperative services on labor and delivery. As such, broader quality metrics to guide overall performance are needed. The American Society of Anesthesiologists Statement on Quality Metrics identified six areas of obstetric anesthesia for quality improvement and encouraged anesthesiologists to monitor practice trends for these items.71 Previous studies have focused on anesthesia interventions as a quality metric,3,7-13 while other studies have focused on self-reported pain.18-20 
Best Practices 
  • Consider a continual institutional audit of the following metrics:
    • Percentage of patients who receive general anesthesia for cesarean delivery for the indication of failed neuraxial anesthesia.
    • Percentage of patients who receive systemic anesthetic adjunct medication for cesarean delivery performed under neuraxial anesthesia including route and dose.
    • Adverse events associated with initiation of general anesthesia for cesarean delivery.
    • Adverse events associated with the administration of systemic anesthetic adjunct medication for cesarean delivery.
  • Consider implementing a process to evaluate and, if indicated, modify institutional practice in response to quality metric data.

References:

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Curated by: Governance

Last updated by: Governance

Date of last update: October 23, 2024