key: cord-0955784-24b19v5d
authors: LaRiviere, Michael J.; Shah, Yash B.; Cummings, Elizabeth R.; Clegg, Kelly; Doucette, Abigail; Struyk, Brian P.; Lustig, Robert A.; Kurtz, Goldie; Hill-Kayser, Christine E.
title: General Anesthesia for Pediatric Radiotherapy in the Era of COVID-19
date: 2022-03-06
journal: Adv Radiat Oncol
DOI: 10.1016/j.adro.2022.100929
sha: d1e84a5673d0d5229b202bab0175a35c37ba9162
doc_id: 955784
cord_uid: 24b19v5d

Purpose Managing pediatric patients requiring daily general anesthesia (GA) for radiation therapy (RT) in the setting of COVID-19 is complex, due to the aerosolizing nature of GA procedures, the risk of cardiopulmonary complications for infected patients, and the treatment of immunocompromised oncology patients in a busy, densely populated radiation oncology clinic. Methods and Materials We developed an institutional protocol to define procedures for COVID testing and protection of patients, caregivers, and staff, hypothesizing that this protocol would allow patients requiring GA to be safely treated, minimizing COVID transmission risk to both patients and staff, at the same time maintaining pre-COVID patient volumes. All patients underwent COVID testing prior to their first treatment and thrice weekly during treatment. For COVID+ patients, RT was delivered in the last end-of-day treatment appointment. A negative pressure room was used for GA induction and recovery, and separate physician/nurse teams were designated for in-room vs. out-of-room patient management. Results Seventy-eight pediatric patients received RT under GA, vs. 69 over the same prior year timeframe, and 2 patients received 2 courses of RT under GA, for a total of 80 courses. The mean age was 4.9 y (range 0.5-19.0 y) and 41/78 (52.6%) were male. Two patients (2.6%) received two courses of radiotherapy under GA, establishing a total of 80 courses. The mean number of treatment fractions was 22.2 (range 1-40). Two of 78 patients (2.6%) tested positive for COVID-19; both were asymptomatic. Both patients completed treatment as prescribed. Neither patient developed cardiopulmonary symptoms complicating anesthesia, and neither patient experienced grade 3+ acute radiation toxicity. Conclusions With careful multidisciplinary planning to mitigate COVID-19 risk, pediatric RT with GA was carried out for a large patient volume without widespread infection, and without increased toxicities from either GA or RT.

The COVID-19 pandemic has disrupted clinicians' approach to the diagnosis and management of cancer.

Radiation Oncology, in particular, has required adaptations to balance the competing demands of providing life-saving daily treatments to patients who may be immunocompromised and at increased risk of severe COVID-19 infection, 1 with the protection of staff who treat confirmed COVID-positive patients. Common protective precautions include screening all hospital entrants, regularly testing patients, requiring masks for patients and caregivers, enforcing social distancing, minimizing time spent in public spaces, enforcing mandatory staff use of personal protective equipment (PPE), and limiting the number of staff who interact with patients with suspected or confirmed COVID-19. 2, 3 With the emergence of the Delta variant and the specter of new COVID variants on the horizon, evaluating these precautions brings a renewed urgency. 4 Novel variants' high rate of transmission and potential to infect vaccinated individuals demand evidencebased precautions to protect vulnerable cancer patients. 5 Pediatric patients treated with radiotherapy (RT) require additional unique precautions, particularly if they require daily general anesthesia (GA) if their age or developmental stage prevents them from maintaining the treatment position during RT setup and treatment. Anesthesia induction and recovery involve potentially aerosol-generating procedures that have the potential to increase the risk of viral transmission to nearby staff and patients. [6] [7] [8] [9] Although the degree to which these procedures generate clinically significant aerosols is not well understood, [6] [7] [8] [9] odds of viral transmission are estimated to be elevated 6.6 times during intubation. 10 Moreover, supraglottic airway (SGA) devices, including laryngeal mask airways (LMAs) commonly used for pediatric GA, may actually be more aerosolizing than endotracheal intubation. 11,12 COVID infection may introduce additional cardiopulmonary risks among patients receiving GA, as even clinically asymptomatic patients may have CT imaging evidence of pulmonary injury, 13 and GA may interfere with normal immune function. 14 Given the risks and challenges associated with treating pediatric patients with COVID-19 under GA, our tertiary academic center developed and implemented a detailed, systematic testing and management protocol to reduce the risk of COVID-19 transmission among patients and staff. We hypothesized that that this protocol would allow patients requiring GA to be safely treated, minimizing COVID transmission risk to both patients and staff, at the same time maintaining pre-COVID patient volumes to allow for the continuation of essential and timely radiation treatments. Figures 1-2) . All patients underwent COVID polymerase chain reaction (PCR) testing 3 times per week, initiated prior to the first treatment and continued throughout the treatment course, with results typically available within 4-6 hours. Testing was initially conducted by nasopharyngeal swab but later transitioned to anterior nasal swab. Adult caregivers were not COVID-tested, but all hospital entrants underwent verbal screening. Only asymptomatic caregivers were allowed entry. Staff and patient protections still treated asymptomatic caregivers of COVID-positive patients as potentially COVID-positive themselves. As directed by hospital-wide guidelines, only a single adult caregiver was permitted for each patient. For confirmed COVID-positive patients, only the same caregiver was allowed to accompany the patient through the duration of the treatment under COVID precautions.

All COVID-positive patients and their caregivers were required to don masks and gloves during the duration of the visit, unless, for the patient, radiation setup and treatment required their removal. The number of rooms or corridors occupied by each patient was minimized, as the patient was escorted directly from the parking lot to the GA induction/recovery room, to the treatment vault, and vice versa.

Staff -expanded PPE‖ included gown, gloves, eye protection, and N95 masks or, when N95s were initially unavailable, powered air purifying respirators (PAPRs) (Supplemental Figure 1) . PAPR use required additional staff to ensure correct donning and doffing. Separate physician and nurse teams were designated for in-room versus out-of-room patient management. When exiting patient rooms, in-room staff were required to doff PPE in the anteroom. Staff -modified expanded PPE‖ included gown, gloves, eye protection, and surgical masks.

COVID-positive patients were treated in the final evening appointment slot each day to allow the facility to remain empty after treatment, until they were cleaned overnight. Because the usual induction and recovery rooms lacked negative pressure ventilation, a separate negative pressure room was designated for both GA induction and recovery. MD anesthesiologists, rather than CRNA anesthetists, were responsible for COVIDpositive patients. Treatment, the Anesthesia Induction protocol details the use of expanded PPE, and which staff may remain in the negative pressure room during induction. In the next Patient Treatment subsection, Transport to Treatment Room, the children's hospital/pediatric anesthesia team transports the patient to the treatment room, where 2 -dirty‖ radiation therapists wear expanded PPE, and 2 -clean‖ radiation therapists remain in the control room with modified expanded PPE. The -dirty‖ radiation therapists wait in the designated -dirty‖ area outside of the treatment room, and re-enter for multi-field treatments or at the end of treatment. As staff gained experience with these procedures, the protocol was amended to require only 2, rather than 4 radiation therapiststhe first remains -dirty‖ and the second alternates between -dirty‖ and -clean‖ with PPE donning and doffing. The third Patient Treatment subsection describes Transport to Recovery Room, where the patient is brought back to the negative pressure room. To ensure fully functional negative pressure, the children's hospital/pediatric anesthesia team must wait 4 minutes before beginning the extubation sequence. Additional anesthesia team members, wearing modified expanded PPE, wait outside of the negative pressure room in case of emergency. No less than 15 minutes after extubation, after the patient has recovered from anesthesia, the caregiver is escorted to the negative pressure room. The final Patient Treatment subsection outlines the steps for Patient Departure. Briefly, after 2 nurses escort the patient and caregiver back to the exit via the designated route, the negative pressure, recovery, and treatment rooms are cleaned, Environmental Services and Physics are notified of room closure time, and therapy managers are notified. Therapy managers ensure the treatment room is clean before resuming treatments the next morning.

Seventy-eight pediatric patients received RT under GA, compared to 69 patients over the same timeframe the previous year (Table 1) . For the present cohort, the mean age was 4.9 y (range 0.5-19.0 y) and 41/78 (52.6%) were male. Two patients (2.6%) received two courses of RT under GA, establishing a total of 80 courses.

Nine of 80 (11.3%) courses involved total body irradiation, 24/80 (30.0%) were delivered to the chest, abdomen, and/or pelvis, 21/80 (26.3%) to the craniospinal axis, 17/80 (21.3%) to the brain, 5/80 (6.3%) to the head/neck, and 4/80 (5%) to other sites. Sixty-four of 80 (80%) courses were delivered with curative intent, with 39/80 (48.8%) utilizing proton therapy, 18/80 (22.5%) using photons, and 23/80 (28.8%) using both modalities. The mean number of treatment fractions was 22.2 (range 1-40). Two of 78 patients (2.6%) tested positive for COVID-19, although both were asymptomatic.

The first COVID-positive patient was a 3 yo female with high-risk neuroblastoma. Her simulation was initially delayed by 8 days as she had a known household contact with COVID, and delay was not expected to impact disease-related outcomes. RT was ultimately initiated 15 days after simulation, but the patient herself tested positive for COVID after the first fraction of RT. A 2-day treatment interruption was required to finalize and implement institutional COVID guidelines. Including the weekend and an additional missed fraction for nil per os (NPO) violation, resumption of treatment was delayed by a total of 5 days. Proton therapy to 21.6 Gy/12 fx for this COVID-positive patient then continued without incident. The only toxicities noted were grade 1 anorexia and grade 2 alopecia. Approximately 1/3 of staff members donned PAPRs due to limited N95 supply, fit test failures, or personal preference. Because eye protection was not yet routinely used, 17 staff were quarantined because of exposure on treatment day 1, but no further staff exposures occurred after precautions for this positive test were implemented.

The second COVID-positive patient was a 3 yo male with relapsed medulloblastoma, not previously treated with radiation, who tested positive on initial COVID testing, requiring a 1-day treatment delay to implement COVID precautions. The patient was treated as COVID-positive with appropriate precautions implemented for the following 10 days of treatment. Proton CSI and boost to a cumulative dose of 54 Gy/30 fx was well tolerated, with only grade 1 dermatitis, cough, voice alteration, anorexia, fatigue, and grade 2 alopecia noted.

No staff exposures were recorded. As the supply of N95 masks had improved when he underwent treatment, all staff members wore N95 masks. On-treatment visits (OTVs) were held via telemedicine for patient 1 and in-person for patient 2. No caregivers screened positive, and neither patient presented for treatment without the designated parent. Both patients were managed with LMAs for GA. Neither patient developed cardiopulmonary symptoms complicating GA, and neither patient experienced grade 3+ acute radiation toxicity.

To our knowledge, this is the first publication of a protocol to facilitate the continued, safe RT treatment of pediatric patients under GA in the midst of the COVID-19 pandemic. With careful multidisciplinary planning to mitigate the risk of transmission, pediatric RT with GA was carried out for a large patient volume without widespread infection or increased toxicities from either GA or RT. Only 2 patients from a large cohort tested positive for COVID-19, both at the beginning of the RT course (infection not thought to be related to RT).

With the institutional COVID guidelines finalized and implemented after the first patient tested positive, treatment delay was reduced for the second COVID-positive patient. Staff exposures were minimized, and although staff quarantines were initially required, no positive cases were identified among staff.

The COVID-19 pandemic has introduced significant challenges for healthcare systems worldwide, leading to clinically meaningful interruptions in the management of cancer patients 15 as well as increased COVIDrelated ICU admissions and deaths among this group. 16 Implementation of our protocol was instrumental in allowing treatments for all children receiving GA to continue with minimal delay or interruption, while at the same time minimizing their risk of transmitting or contracting COVID. Our volume of children treated with GA was actually 13% higher compared to the same time-frame the prior year. By contrast, 85% of practices across the United States saw decreased patient volume several months into the COVID-19 pandemic, with an average volume of 68% versus baseline. 17 Moreover, these practices treat primarily adult patients, with no GA.

Although this report is the first to describe a specific protocol for RT in pediatric patients receiving GA, others have published recommendations that are relevant to this patient cohort. For instance, in April of 2020, Johns Hopkins Radiation Oncology Department published guidelines that described selected pediatric patients as high-priority, and for whom RT should be continued even in the setting of COVID infection. 18 In July of 2020, The European Society of Paediatric Oncology (SIOPE) published recommendations for the delivery of RT for pediatric patients. 19 Although GA was not specifically discussed, our management of both COVID-positive patients was consistent with the authors' recommendations that 1) neuroblastoma should be treated with standard dose/fractionation schedules when possible, and 2) radiation for medulloblastoma should not be delayed.

Staff were generally highly receptive to the implementation of this protocol and gained comfort with it over time. There were no notable points of contention in the development of this protocol in collaboration with the Infection Prevention and Control and Radiation Safety teams, as radiation therapists, nurses, and physicians felt that given the risks of COVID, they should proceed as directed by these groups despite certain challenges noted below. Notably, correct donning and doffing of PPE was initially challenging. Based on additional input from the Infection Prevention and Control team, and as supplies of appropriate PPE stabilized after shortages early in the pandemic, the donning/doffing sequence was streamlined. The staffing required by the original protocol was difficult to maintain in the setting of pandemic-related staffing shortages. While the required number of anesthesiologists (2) and nurses (2) has remained unchanged, the protocol was amended to require fewer radiation therapists (2 vs. 4) to be present for each COVID+ GA treatment. As our department has robust processes in place for the review and implementation of new procedures, staff felt that, when sufficient time was allowed to schedule appropriate staffing levels, to procure the requisite supplies, and to rearrange treatment time schedulesspecifically requiring at least 2 days to preparethis protocol was fairly straightforward to implement.

In addition to staff, patients and families have experienced challenges related to this protocol. Because GA requires patients to be nil per os (NPO), and because COVID-positive patients require end-of-day treatment times, adherence to NPO instructions is particularly unpleasant for these children. Another point of contention has been clearance from COVID precautions, as our departmental and adult hospital requirements differ from the children's hospital's requirements. Our practice has been to follow the more conservative protocol that treats patients as COVID-positive for a longer period.

GA is a staff-, time-, and resource-intensive procedure, and access to GA may be limited. Prior to the COVID-19 pandemic, in the setting of higher patient volumes or limited GA staffing, the pediatric radiation oncology team led multidisciplinary communication among the radiation therapy, anesthesia, and nursing teams in order to triage patients by clinical need, delaying treatment start dates if clinically acceptable. In the setting of COVID-19, this multidisciplinary discussion now includes the Infection Prevention and Control team. After this protocol was implemented, our department has assembled a Radiation Oncology COVID committee, which includes a pediatric radiation oncologist, to discuss the triage and management of any COVID-positive patient requiring treatment. A similar committee could be developed to triage access to GA if this becomes a more limited resource.

Safe and timely management of pediatric patients who require RT under GA is seeing renewed importance in light of the multiple variants that have emerged since this patient cohort was analyzed, namely the Delta and Omicron variants, and there remains concern that novel more virulent COVID variants may develop. Indeed, although the Delta variant did not appear to cause more severe disease among children, it caused a marked increase in cases and hospitalizations: among children who were hospitalized between June 20, 2021 and July 31, 2021, approximately 23.2% required intensive care unit admission, 9.8% required ventilator support, and 1.8% died. 20 Likewise, the Omicron variant was even less severe for children, with 10.4% of hospitalized patients under 18 requiring ICU admission and 0 requiring ventilator support; no children died during the Omicron surge between December 26, 2021 and January 15, 2021. 21 Our protocol presents a standardized approach to prevent transmission of a highly infectious respiratory disease for children who require GA for RT. This protocol may be adapted to reflect institution-specific considerations and requirements. Key limitations include the fact that as only 2 patients tested positive for COVID, and both patients were asymptomatic, it is difficult to conclude whether our findings regarding patient and staff safety will generalize to a larger population. Future directions include validation of this approach in the setting of the Delta and Omicron variants, future COVID variants, as well as any other novel respiratory virus outbreaks. To improve on this work, we propose the development of a consortium of institutions treating COVID-positive pediatric patients under GA, to efficiently share information about disease transmission and protocol failures. With this rapid information sharing in place, protocol updates can be made and evaluated in real-time to allow for the continued treatment of pediatric cancer patients.

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