ASRA Pain Medicine Update

The COVID-19 pandemic presents unique challenges to anesthesiologists caring for patients during labor and delivery.  Unlike elective surgical procedures, delivery cannot be rescheduled or delayed.  Labor and delivery is a fast-paced, multidisciplinary environment involving a large number of healthcare workers that must coordinate their efforts across disciplines.  Anesthesiologists taking care of patients in labor and delivery must understand the presentation of COVID-19 in pregnant patients and recognize the potential overlap between COVID-19-related and pregnancy-related symptoms. The anesthesia team must ensure that appropriate institutional protocols are in place to safely provide labor analgesia and anesthesia for cesarean delivery or other necessary surgical procedures.  The policies should focus on how to risk stratify patients, minimize the risk of exposure to patients and healthcare workers, and manage personal protective equipment (PPE).

Information regarding the impact of COVID-19 on pregnant patients and implications for obstetric anesthesia is rapidly evolving.

Prior experience with pandemic viral pneumonias, including the 1918 and 2009 influenza outbreaks^[1,2] and severe acute respiratory syndrome,^[3] raised fears that pregnant women could be at increased risk for morbidity and mortality associated with COVID-19.  Fortunately, data thus far,^[4] while limited, suggests that pregnancy itself is not a risk factor for severe disease and that the presentation of COVID-19 infection in parturients is similar to non-pregnant individuals.  While early experience in China^[5] suggested that the majority of pregnant patients with COVID-19 infection had mild symptoms, most commonly fever and cough, universal screening on admission to labor and delivery in New York suggests that nearly 90% of pregnant women with COVID-19 may be asymptomatic.^[6]  Non-specific symptoms associated with COVID-19 also overlap considerably with symptoms associated with pregnancy and labor.  Pre-eclampsia, for example, can present with headache; subjective dyspnea is common, particularly in the third trimester; and chorioamnionitis can present with fever in labor or immediately postpartum. This overlap may delay recognition of COVID-19 infection in pregnancy in settings where testing is driven by symptoms.

Risk stratification and testing for COVID-19 is essential to guide rational decisions regarding PPE use by healthcare workers.  Screening for COVID-19-related symptoms and exposure  should be performed with focused testing of high-risk individuals. Depending on local epidemiology and testing capacity, universal screening also may be appropriate when feasible.^[7]  Patients with suspected or confirmed COVID-19 infection should be placed in isolation rooms, and PPE appropriate for droplet and contact precautions should be used for all patient contact.  Aerosol-generating procedures, such as endotracheal intubation, should be performed in a negative-pressure environment with PPE appropriate for airborne-precautions (including an N95 respirator or equivalent).  The likelihood that forceful exhalations that frequently occur during the second stage of labor may aerosolize viral particles^[8] is controversial, and the Centers for Disease Control and Prevention (CDC) does not classify the second stage of labor as an aerosol-generating procedure meriting prioritization of N95 respirators during shortages.^[9] 

COVID-19 infection is not considered a contraindication to labor neuraxial analgesia.  Neurologic complications or deterioration have not been reported following neuraxial procedures in obstetric patients with COVID-19 infection.^[10] While there may be a theoretical risk of causing meningitis or encephalitis,^[11] viremia is rare in patients with severe disease,^[12] and viral RNA was not detected in the cerebrospinal fluid of 7 of 7 severely ill encephalopathic patients with COVID-19 infections.^[13]  A functional labor epidural decreases the likelihood that intubation will be necessary should intrapartum cesarean delivery be required. In the context of a COVID-19 infection, this has a significant advantage of avoiding further compromise of respiratory function resulting from intubation and mechanical ventilation.  Avoiding an aerosol-generating procedure also decreases the risk for healthcare providers and others present on the labor and delivery floor.  Therefore, the benefits of neuraxial labor analgesia in a COVID-19 infected patient outweigh any hypothetical concerns.  From a practical perspective, anesthesiologists should ensure that they are wearing appropriate PPE and that the patient wears a mask at all times.  Depending on local epidemiology and practice patterns, some institutions may also consider altering routine practice to maximize social distancing efforts by taking steps such as conducting pre-anesthetic and intrapartum evaluations over the phone instead of in person encounters.

Anesthesiologists must remain cognizant of standard contraindications to neuraxial procedures including severe thrombocytopenia and recent use of anticoagulants.^[14]  Thrombocytopenia has been reported in parturients with COVID-19 infection^[15] and, in the general population, appears to be more common in association with severe disease.^[16]  The hypercoagulable state that has been described in association with COVID-19 infection has led some centers to expand use of thromboprophylaxis in COVID-19-positive parturients.  Anesthesiologists performing neuraxial procedures must be vigilant regarding the potential for developing thrombocytopenia and use of anticoagulant therapy in a COVID-19-positive parturient. 

An increasing number of centers in the United States have adopted nitrous oxide for labor analgesia.^[17]  Continuing the use of nitrous oxide during the COVID-19 pandemic is controversial. The Society for Obstetric Anesthesia and Perinatology (SOAP) recommends considering suspending use given “insufficient information about the cleaning, filtering, and potential aerosolization”^[18] associated with nitrous oxide.  The Royal College of Gynecology and the Royal College of Anaesthetists recommend use of a single patient filter, which is standard practice in the United Kingdom, and considers there to be no evidence that labor nitrous oxide use generates aerosols.^[19]  Individual centers should weigh the risks and benefits of continuing to offer nitrous oxide for labor analgesia in the context of their institutional cleaning and filtering protocols, as well as local epidemiology and testing for COVID-19.

Neuraxial anesthesia is preferred for cesarean delivery, regardless of COVID-19 infection status.  As discussed above, neuraxial procedures are not contraindicated by COVID-19 infection; providers, however, always need to be prepared for conversion to a general anesthetic.  Given the possible need to convert emergently to general anesthesia, as well as the frequent need to remove a patient’s mask during episodes of vomiting, centers should consider use of aerosol protection for all providers in the operating room during cesarean delivery.²⁰ A retrospective study from Wuhan, which was not randomized or controlled for other sources of COVID-19 exposure, suggested that use of enhanced PPE may be associated with a decreased rate of COVID-19 acquisition among anesthesiologists who provided spinal anesthesia.^[21]  Emergent cesarean deliveries require coordinated efforts among many providers.  Donning and doffing appropriate PPE and ensuring safe transport of patients with or suspected of having COVID-19 infection, requires organized efforts among providers.  Unavoidable delays will occur for emergency procedures during the COVID-19 pandemic. Efforts should be made to minimize the need for emergent procedures. Having simulations, drills, and multidisciplinary planning are recommended to prevent negative outcomes.^[18]

Several commonly used obstetric medications have special considerations in patients with COVID-19.  Carboprost is used as a uterotonic in the management of postpartum hemorrhage and may cause bronchospasm. Its use was associated with unexpectedly severe bronchospasm following intubation in a patient with COVID-19 infection.^[22]  Non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of treatment for post-cesarean pain control. They also are used for tocolysis and prevention of preeclampsia in some high-risk patients. Although possible association with worsening of infection in patients with COVID-19 was hypothesized, these reports have not been substantiated and the Society for Maternal Fetal Medicine does not currently recommend suspending use of NSAIDs in patients with confirmed or suspected COVID-19 infection.^[23]  Magnesium sulfate is used for seizure prophylaxis as well as neonatal neuroprotection. Magnesium can accumulate in renal failure, which is common in severe COVID-19 infection. Magnesium toxicity can also lead to respiratory compromise.  The use of magnesium sulfate in patients with COVID-19 should be individualized while taking into account the patient’s renal function and respiratory status.  Steroids are given for fetal lung maturity and occasionally as an antiemetic for cesarean delivery.  While the routine use of steroids is not currently recommended in the general population with severe COVID-19,^[24] the Society for Maternal Fetal Medicine recommends consideration of their use for fetal benefit in women with COVID-19 at risk of preterm delivery prior to 34 weeks of gestation.^[23] Alternative agents are recommended for antiemetic use.^[18]

Information regarding the impact of COVID-19 on pregnant patients and implications for obstetric anesthesia is rapidly evolving.  Anesthesiologists should be familiar with their local hospital guidelines and consult sources such as SOAP,^[18] ACOG,^[7] and the CDC.^[9]  With up-to-date knowledge and appropriate precautions, anesthesiologists on labor and delivery will be well-prepared to care for obstetric patients during the COVID-19 pandemic. 

References

1. Harris JW. Influenza occurring in pregnant women. JAMA 1919;72:978–80.
2. Jamieson DJ, Honein MA, Rasmussen SA, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009;374:451–8. doi: 10.1016/S0140-6736(09)61304-0.
3. Lam CM, Wong SF, Leung TN, et al. A case-controlled study comparing clinical course and outcomes of pregnant and non-pregnant women with severe acute respiratory syndrome. BJOG 2004;111:771–4. doi: 10.1111/j.1471-0528.2004.00199.x.
4. Elshafeey F, Magdi R, Hindi N, et al. A systematic scoping review of COVID-19 during pregnancy and childbirth. Int J Gynecol Obstet 2020;23:e204621–6. doi:10.1002/ijgo.13182
5. Chen L, Li Q, Zheng D, et al. Clinical characteristics of pregnant women with COVID-19 in Wuhan, China. N Engl J Med 2020;382:e100. doi: 10.1056/NEJMc2009226.
6. Sutton D, Fuchs K, D'Alton M, Goffman D. Universal screening for SARS-CoV-2 in women admitted for delivery. N Engl J Med 2020;382(22):2163-4. doi: 10.1056/NEJMc2009316. 
7. American College of Obstetricians and Gynecologists. Novel coronavirus 2019 (COVID-19): Practice advisory. Available at: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2020/03/novel-coronavirus-2019. Accessed May 28, 2020.
8. Palatnik A, McIntosh JJ. Protecting labor and delivery personnel from COVID-19 during the second stage of labor. Am J Perinatol 2020; Apr 10. doi: 10.1055/s-0040-1709689. Online ahead of print.
9. Centers for Disease Control and Prevention. Clinical questions about COVID-19: Questions and answers. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html. Accessed May 28, 2020.
10. Bauer ME, Chiware R, Pancaro C. Neuraxial procedures in COVID-19 positive parturients. Anesth Analg 2020. doi: 10.1213/ANE.0000000000004831. Online ahead of print.
11. Yashavantha Rao HC & Jayabaskaran C. The emergence of a novel coronavirus (SARS-CoV-2) disease and their neuroinvasive propensity may affect in COVID-19 patients. J Med Virol 2020;92:786-90. doi: 10.1002/jmv.25918.
12. Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA 2020;323:1843-44. doi: 10.1001/jama.2020.3786. 
13. Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med 2020;382:2268-70. doi: 10.1056/NEJMc2008597.
14. Leffert LR, Dubois HM, Butwick AJ, Carvalho B, Houle TT, Landau R. Neuraxial anesthesia in obstetric patients receiving thromboprophylaxis with unfractionated or low-molecular-weight heparin: a systematic review of spinal epidural hematoma. Anesth Analg 2017;125(1):223–31. doi: 10.1213/ANE.0000000000002173.
15. Kim J-H, Shrestha N, Girshin M. Unexpected severe thrombocytopenia in the COVID-19 positive parturient. Anesthesia & Analgesia 2020 May 4;10.1213/ANE.0000000000004948.
     doi: 10.1213/ANE.0000000000004948. Online ahead of print.
16. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta 2020;506:145–8.
17. Richardson MG, Raymond BL, Baysinger CL, Kook BT, Chestnut DH. A qualitative analysis of parturients' experiences using nitrous oxide for labor analgesia: it is not just about pain relief. Birth 2019;46:97–104. doi: 10.1111/birt.12374. 
18. Society for Obstetric Anaesthesia and Perinatology. Interim considerations for obstetric anesthesia care related to COVID19. Available at: https://soap.org/education/provider-education/expert-summaries/interim-considerations-for-obstetric-anesthesia-care-related-to-covid19/. Accessed May 28, 2020.
19. The Royal College of Midwives & Royal College of Obstetricians & Gynecologists. Coronavirus (COVID-19) infection in pregnancy. Available at: https://www.rcog.org.uk/globalassets/documents/guidelines/2020-05-13-coronavirus-covid-19-infection-in-pregnancy.pdf. Accessed May 28, 2020.
20. Bauer M, Bernstein K, Dinges E, et al. Obstetric anesthesia during the COVID-19 pandemic. Anesth Anal 2020;131(1):7-15. doi: 10.1213/ANE.0000000000004856.
21. Zhong Q, Liu YY, Luo Q, et al. Spinal anaesthesia for patients with coronavirus disease 2019 and possible transmission rates in anaesthetists: retrospective, single-centre, observational cohort study. Br J Anaesth 2020;124(6)670-5. doi: 10.1016/j.bja.2020.03.007.
22. Breslin N, Baptiste C, Miller R, et al. COVID-19 in pregnancy: early lessons. Am J Obstet Gynecol MFM 2020;2(2)100111. doi: 10.1016/j.ajogmf.2020.100111
23. Society for Maternal-Fetal Medicine. Society for Maternal-Fetal Medicine management considerations for pregnant patients with COVID-19. Available at: https://s3.amazonaws.com/cdn.smfm.org/media/2336/SMFM_COVID_Management_of_COVID_pos_preg_patients_4-30-20_final.pdf. Accessed May 28, 2020.
24. National Institutes of Health. COVID-19 treatment guidelines. Available at: https://www.covid19treatmentguidelines.nih.gov/. Accessed May 28, 2020.