SPA Spring Meeting Reviews

Friday Session IV - Vaccination Nation

By Faye Evans, MD
Boston Children’s Hospital

Measles and Anesthesia: Let’s Be Prepared

This session began with Karla Wyatt, MD, MS, (Texas Children’s Hospital) presenting a one-year-old child for urgent removal of a foreign body in the airway in the middle of the night. The child was in obvious respiratory distress with oxygen saturations of 88%, retractions and drooling. On physical exam the child was noted to have a rash suggestive of measles. Measles (Rubeola) is a highly contagious virus which belongs to the paramyxovirus family. It is spread by aerosol or droplet contact and can remain suspended in the ambient environment for up to two hours.  It is characterized by the three C’s: cough, conjunctivitis, and coryza. With infection, there is a 10-14 day incubation period, followed by a 2-4 day prodrome of non-specific symptoms and then the rash appears. The patient is most contagious the four days prior to the rash and for four days after the rash. Diagnosis is made by both clinical findings: Maculopapular rash for three days, temperature > 101F, and the three “C’s”, and laboratory tests +serological measles IgM and IgG seroconversion. Once confirmed, health care providers are required to report measles to local health department within 24 hours.

Dr. Wyatt explained that measles can cause severe disease especially in pregnant females, the immunocompromised, and children <1 year.  It is a multi-systemic viral process targeting epithelial and reticuloendothelial cells and leukocytes. One out of four infected individuals are hospitalized. The leading causes of hospitalization and death are pulmonary complications, followed by airway complications from laryngotracheobronchitis, and ocular complications which can lead to blindness. Patients are also at risk for neurologic complications such as encephalitis. Patients commonly develop diarrhea and are at risk for dehydration.

Dr. Wyatt then presented a historical overview of measles and our current understanding of the virus and its effects. Dr. Rhazes, a Persian philosopher and scientist, is credited with publishing the first treatise on the clinical characteristics of human measles in 910.  However, the virus had been around well before Dr. Rhazes' publication. Morbilliviruses (derived from the Latin word for 'little plague') represent a genus of viruses causing distinctive diseases with very high morbidity and mortality, especially in naïve populations. There are numerous historical descriptions of morbilliviral epidemics in both humans and animals. For example, rinderpest virus dates back to 3000 BC.  This virus was endemic in Asia and caused a “cattle” plaque that spread with the transport of cattle and colonization throughout Africa and Europe. Human measles virus (HMV), rinderpest virus (RPV) of cattle, and canine distemper virus (CDV) are very closely related and have all caused devastating disease epidemics for centuries. They are ‘crowd diseases’. They most likely arose after the development of agriculture when the large dense interacting populations of humans and animals required to maintain the viruses as endemic infections were established.

In the 17th and 18th centuries, measles was one of the leading causes of death. The development of a measles vaccine began with Dr. Francis Home who in 1765 identified the infectious agent in the blood. However,  it wasn’t until 1963 that Dr. Enders Hileman developed an FDA-approved vaccine. By 1970, Merck introduced the MMR vaccine and by 1983, there were zero cases of measles in the US. By 2000, widespread vaccination resulted in measles being declared eliminated from the US. However, measles elimination, which is defined as absence of continuous measles transmission for greater than 12 months, is a global problem. This does not necessarily equate to zero incidence.  In the US from the 1960s through 2000, efficacy was evident.  However, by 1989, a  second dose of MMR vaccine was recommended in response to increase in outbreaks amongst immunized children.

In recent years, the rise in the “Anti-vaxxer” movement has caused a resurgence in measles outbreaks in the US. However, this idea of opposition to mandatory vaccination is not new. With the introduction of the smallpox vaccination in the 18th and 19th centuries, there were some who felt that mandatory vaccines encroached on liberty and freedom of choice. The anti-vaccinationists' rejection of government and medical coercion in relation to health reflected a wider suspicion of state intervention in personal and family affairs. Activists were often religious dissenters, trade unionists, and radicals. They were often opponents of vivisection, supporters of temperance, vegetarianism and alternative medicine. As well as being an effective parliamentary lobby, anti-vaccinationism was a militant mass movement, given to carnivalesque demonstrations and riotous protests. During this time several anti-vaccination societies developed.

Though today's anti-vaccination campaigns get some support from quirky aristocrats, their base of support is almost exclusively middle class. Activists typically object to particular vaccines (in Britain mainly MMR, in the USA mainly those containing mercury). They have no objection to state intervention in any other area. While some anti-vaccinationists favor homeopathy or other alternative therapies, many seek to justify their concerns about vaccine safety with reference to mainstream medical science.  Some of the most prominent campaigns are careful to point out that they are not 'anti-vaccine' but simply want to promote 'informed choice' by parents. In contrast to the collective campaigns of the past, today's have a strongly individualistic character. Rather than demanding the abandonment of the national immunization programs, they merely request the choice of mercury-free vaccines, or single agents rather than MMR. 

The global impact of this movement is huge. Eight percent of children in the US are currently not vaccinated. While measles is endemic in several areas of the world due to poor access to medical care and political instability, there is also a rise in incidence in the US. Until 2017, there were only about 100 cases reported in the US per year. In 2019, there was a 2.5 x increase in incidence with over 1200 cases of measles being reported.  Seventy percent of those affected were children and 10% required hospitalization.

The resurgence of vaccine-preventable diseases presents the pediatric anesthesiologist and critical care intensivist with unique challenges as they will be given responsibility for caring for these patients with severe complications that they likely will have not previously encountered.  What should we as anesthesiologists know about these patients in order to care for them safely? The measles virus, when aerosolized, can travel further distances than many viruses. Airborne and contact precautions are a must. The CDC recommends gloves, gowns, and N95 masks or power purifying masks when caring for these patients. When they need to be transported through the hospital, transport routes to minimize contact with other individuals must be considered.

Operating rooms are designed to have positive pressure ventilation to create a 'clean' protective environment. A higher pressure inside the operating room than that of the surrounding environment means air can leave the room without circulating back in. Therefore, airborne particles that originate in the room will be filtered out.  Unfortunately, this system allows viruses such as measles to easily circulate into hallways.  Negative pressure ventilation is used for highly infective rooms in the hospital (e.g., isolation rooms for tuberculosis patients) and should be used for all intubations and extubation of patients with measles if possible.

As far as treatment for these patients, it is supportive care only and fortunately it usually resolves within 14 days. Mortality is usually associated with respiratory complications: pneumonitis or laryngotracheobronchitis (croup). Vitamin A administration is recommended as it can lessen the sequelae of some of the complications.  For those patients who do require intubation, practitioners should be aware that these patients can desaturate rapidly due to accompanying  interstitial lung disease. Also, there can be difficulty passing endotracheal tubes due to inflammation so a smaller endotracheal tube may be warranted. In addition, these patients are at increased risk of extra alveolar manifestations such as pneumothorax or pneumomediastinum.

Healthcare providers or patients who are not immunized and are exposed should receive an MMR within 72 hours of exposure. If healthcare providers are pregnant or immunocompromised, they should not be given an MMR as there is a very small risk of developing the virus from the vaccine. For both of these groups, IVIG can be considered. For patients under 12 months, IgM should be given instead of IVIG. All exposed,  non-immunized healthcare workers should be excluded from work for 5-21 days. For those healthcare workers and patients who are appropriately up to date on their MMR immunization, no additional treatment is necessary.

Be Wise, Immunize! A Review of the Interaction Between Anesthetics and Vaccines

The second half of the session was a presentation by Rebecca Evans, MD, MS, (University of Vermont Medical School) titled “Be Wise, Immunize!”  Her goal was to review the evidence regarding interactions between anesthetics and vaccines. She began the session by providing a brief history of vaccinations in people. While the first report at variolation or inoculation was attempted as far back as 1022 AD, it was not until 1796 that Edward Jenner preformed the first vaccination against smallpox. 

Dr. Evans then briefly reviewed how vaccines work. While a person’s innate immune system provides non-specific barriers to preventing pathogens from entering, the adaptive immune system is the memory portion that eliminates identified pathogens. There are currently 16 vaccine preventable diseases. Most of the vaccinations are for single pathogens except the MMRV (measles, mumps, rubella, and varicella) that is administered together as a single vaccine. There are four main types of vaccines: live-attenuated vaccines, inactivated/killed vaccines, subunit/conjugate, and toxoid (inactivated toxin).  She went on to review the routine vaccination schedule for these available vaccines.

Dr. Evans then presented data to illustrate that the incidence of vaccine-preventable diseases such as measles, mumps, and whooping cough are on the rise. It is not that the vaccinations are not working, rather, children are not getting immunized. Reasons for this include distrust of organizations recommending vaccinations, concern over potential adverse effects, religious reasons, cost, and that the disease itself is to be perceived to be only mild and self-limiting.  Herd immunity is no longer as effective as it requires a high enough proportion of individuals in a population receiving the vaccination and being immune.  With herd immunity, the majority will protect the few susceptible people because the pathogen is less likely to find a susceptible person.

Anesthesiologists need to be aware and realize there is an increased likelihood they will be presented with patients with these preventable diseases and their sequelae that they may have never previously seen such as measles, pertussis, diphtheria, and congenital rubella syndrome.  As anesthesiologists we need to be aware of these pathogens and do all that we can to reduce the spread when faced with patients who are infected.  Strict hand hygiene, contact and droplet precautions are imperative.

Dr. Evans then presented some interesting data on immunization practices among institutions.  Royal Children’s Hospital in Melbourne, Australia has one of the most proactive plans in place for improving vaccination compliance. They ask about the patient’s vaccination history during their preoperative visit.  If the patient is not up to date on their vaccinations, they will schedule necessary vaccinations at the end of the surgical procedure at the time of discharge.

Another debated topic is risks associated with vaccination during the perioperative period, including how long should you wait after receiving a vaccination to have elective surgery and how long after elective surgery should one should wait to receive a vaccination. Dr. Evans explained  that there is no consistency among institutions, societies, or countries. There are reportedly theoretical risks of decreased immune response for 48 hours after surgery and concerns around fever in the post-operative period masking more serious complications. However, there is no hard data supporting these concerns.  The literature supports that perioperative vaccination is fairly safe but there is currently no consensus what this specifically means. 

Dr. Evans concluded her presentation with a map of states that allow religious and/or personal belief exemptions for vaccinations. Many states are moving towards removing religious and personal belief exemptions, with California, Maine, and New York passing legislation in the past year.  Other countries, such as Australia, have instituted a strict vaccination policy “No Jab, No play, No Jab, No pay” that has increased the rate of children receiving vaccines significantly. While the policy had mixed opinion when it was implemented, the reality is that it increased the numbers of children being vaccinated from half of children in the mid-1990s to close to 95% in 2019.  There is now a perioperative system in place in Australia, discussed above, to catch children who need vaccination along with a proactive plan for making sure they receive them.

The session ended with a great discussion that included these questions posed by the audience:

  1. Where should these patients be intubated?
  2. If you are immune why is PPE required?
  3. If vaccines were to be ordered preop (i.e. Tetanus for a dog bite), who should be responsible for ordering and giving these vaccines – preop, pediatrician, nurse, anesthesiologists?.
  4. Should the AAP make a statement supporting perioperative vaccinations?
  5. I would think that receiving a vaccination in the perioperative period is better than no vaccination at all. What are your thoughts?
  6. Should you make a difference between active and passive vaccines?
  7. If you are administering a vaccine under anesthesia, who should administer it?
  8. If you are intubating a patient with the measles, where should they be intubated?

In summary, per CDC, patients with the measles and other highly infective viruses that are aerosolized should be intubated in the negative pressure room with proper personal protective equipment including an N95 or PAPR. The highest transmission of aerosolized particles occurs during intubation, extubation, bronchoscopy and tracheostomy. As such, providers should try to limit these procedures to negative pressure room isolation rooms to prevent aerosol spread.

If you are immune, personal protective equipment may still be required when caring for these patients; (1) Vaccine between 1963-67 was inactivated and not as effective-which can resultant in a secondary form of measles infection, (2) not all hospital employees are required to have MMR vaccination, (3) people who received the vaccine before 1989 only received one dose which confers 93% immunity but there still is the possibility of infection.

In regard to the questions addressing the administration of vaccines in the perioperative period, anesthesia and surgery exert immunomodulatory effects that may interfere with vaccine efficacy and safety. Very few studies have assessed the influence of anesthesia and surgery on pediatric vaccine responses. Additionally,  the misinterpretation of postoperative adverse events (i.e. fever) may be confounded in the setting of recent vaccine administration. However, it is thought that the potential immunomodulating effect is minimal and short lived without evidence for contraindication of vaccination of healthy children scheduled for elective surgery.

Nevertheless, some proponents suggest a minimal delay of two days for inactivated vaccines and 2-3 weeks for live attenuated viral vaccines between administration and anesthesia. In contrast, The Association of Paediatric Anaesthetists of Great Britain and Ireland recommends delaying elective surgery for two days after immunization with inactivated vaccines. They do not recommend delaying surgery after immunization with live vaccines because of a lower risk of febrile reactions.

This obviously requires an individualized approach as the risks of delaying surgery must also be considered. Various US hospitals have enacted perioperative policies but there is no consensus as to what is ideal for practice management. There are times when the anesthesiologist will administer a vaccine perioperatively, for example tetanus following a dog bite that is planned for operating room intervention. In this setting the anesthesiologist or bedside nurse often administers the medication which is ordered by the surgical team. The surgical team reviews the risks/benefits with the family prior to administration.

Given the current resurgence of vaccine preventable diseases, the question is raised as to whether or not review of children’s vaccination schedules and administration perioperatively is better than the risk of children not being vaccinated.  The workflow of the pediatric anesthesiologist and hospital infrastructure does not always permit time to review the vaccination record; however, this practice of post-operative vaccination (per vaccine schedule) is well accepted in Melbourne, Australia and is plausible for the US.  When perioperative administration of vaccines occurs, designation of who discusses the risks/benefits with families, orders and administers the vaccine, would need to be factored into the workflow.

Due to the ranges of practice and accepted understanding of vaccines in the perioperative period a consensus statement by the Society for Pediatric Anesthesia/AAP would better enable uniformity/standardization of approach amongst US practitioners.

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