Radiotherapy and Oncology xxx (2014) xxx–xxx
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Original article
Non-invasive anesthesia for children undergoing proton radiation therapy Pascal Owusu-Agyemang a,⇑, David Grosshans b, Radha Arunkumar a, Elizabeth Rebello a, Shannon Popovich a, Acsa Zavala a, Cynthia Williams a, Javier Ruiz a, Mike Hernandez c, Anita Mahajan b,1, Vivian Porche a,1 a Department of Anesthesiology & Perioperative Medicine; b Department of Radiation Oncology; c Department of Biostatistics, The University of Texas MD Anderson Cancer Center, United States
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Article history: Received 28 November 2013 Received in revised form 21 January 2014 Accepted 21 January 2014 Available online xxxx Keywords: Anesthesia Children Proton radiotherapy
a b s t r a c t Background: Proton therapy is a newer modality of radiotherapy during which anesthesiologists face specific challenges related to the setup and duration of treatment sessions. Purpose: Describe our anesthesia practice for children treated in a standalone proton therapy center, and report on complications encountered during anesthesia. Materials and methods: A retrospective review of anesthetic records for patients 618 years of age treated with proton therapy at our institution between January 2006 and April 2013 was performed. Results: A total of 9328 anesthetics were administered to 340 children with a median age of 3.6 years (range, 0.4–14.2). The median daily anesthesia time was 47 min (range, 15–79). The average time between start of anesthesia to the start of radiotherapy was 7.2 min (range, 1–83 min). All patients received Total Intravenous Anesthesia (TIVA) with spontaneous ventilation, with 96.7% receiving supplemental oxygen by non-invasive methods. None required daily endotracheal intubation. Two episodes of bradycardia, and one episode each of; seizure, laryngospasm and bronchospasm were identified for a cumulative incidence of 0.05%. Conclusions: In this large series of children undergoing proton therapy at a freestanding center, TIVA without daily endotracheal intubation provided a safe, efficient, and less invasive option of anesthetic care. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2014) xxx–xxx
Proton therapy is a radiation modality gaining increasing popularity, particularly for the treatment of pediatric cancer patients. Particle therapy, including proton therapy has unique physical properties, which allow for the reduction or elimination of unnecessary dose to normal tissues. It is believed that reduced normal tissue exposure will translate into both decreased rates of both early and late treatment induced toxicities. As such, increasingly young patients are commonly referred, many of who require anesthesia given the need for prolonged immobilization with treatment sessions ranging from 30 to 90 min in length. Several authors have described techniques for anesthetizing children undergoing conventional radiation therapy [1–6]. Anesthesia for proton therapy is unique due to the specific patient set up requirements and potentially longer duration of individual treatments. Moreover, currently the majority of proton therapy ⇑ Corresponding author. Address: Department of Anesthesiology & Perioperative Medicine, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 0409, Houston, TX 77030, United States. E-mail address: [email protected] (P. Owusu-Agyemang). 1 These authors contributed equally.
centers are not within inpatient facilities and as such the capacity for emergency response is limited. There are a limited number of publications on the safety and techniques of providing anesthesia for proton therapy. Investigators from the Indiana University Health Proton center have described their initial experience, recording a low rate of anesthetic related complications at their offsite facility [7]. In their report, anesthesia was induced, a laryngeal mask airway (LMA) placed and anesthesia maintained using inhalational sevoflurane [7]. In contrast, investigators from the University’s Children Hospital and the Paul Scherrer Institute in Switzerland reported on the use of propofol sedation in 10 pediatric patients treated with proton therapy without placement of an artificial airway [8,9]. Such an approach avoids repeated daily instrument-induced irritation of the airway and facilitates immobilization with thermoplastic masks. Additional benefits of avoiding artificial airways may include a reduction in the total amount of anesthetic necessary to maintain adequate sedation and decreased overall room time. As new proton centers continue to emerge, there is a need for further publications describing the anesthetic management for
http://dx.doi.org/10.1016/j.radonc.2014.01.016 0167-8140/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Owusu-Agyemang P et al. Non-invasive anesthesia for children undergoing proton radiation therapy. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.01.016
2
Anesthesia for pediatric proton radiotherapy
children undergoing proton therapy. The primary objective of our study was to review and describe the anesthetic management of children undergoing proton radiation therapy at our center and report on anesthesia-related complications. Materials and methods After approval by the University of Texas MD Anderson Cancer Center Institutional Review Board, we retrospectively reviewed the records of children 18 years of age and younger treated with proton therapy between September 2006 and April 2013. Patient demographics, medical history, site of irradiation, number of anesthetic sessions and route of administration were recorded. Airway management, medications administered, duration of anesthetics, and major complications occurring during anesthesia were recorded. Major complications were defined as the following: cardiopulmonary resuscitation, urgent intubation, unexpected admission to the hospital, the administration of epinephrine or atropine, laryngospasm, pulmonary aspiration, and bronchospasm. Coughing, which required suctioning, and brief spells of apnea or desaturation were not classified as major complications. Likewise, episodes of hypotension or bradycardia, which did not require the administration of epinephrine or atropine, were not classified as major complications. Anesthetic personnel and patient management The proton therapy center is a standalone facility located one mile from the main MD Anderson Hospital Campus. The anesthesia team consists of a physician with pediatric anesthesia expertise and a Certified Registered Nurse Anesthetist (CRNA). Other medical personnel at the facility include; radiation oncologists, radiation therapists, and registered nurses. Referrals for proton therapy under anesthesia are based on the age of the patient, prior history of requiring anesthesia for imaging, the emotional maturity of the child, and the duration and site of treatment. We treat a number of international patients at our proton therapy center, and we have noted anecdotally that European patients above the age of 5 years often do not require anesthesia. It is however not uncommon for North American children over the age of 7 to undergo these procedures under anesthesia. In the event that anesthesia is not required, child life specialists are on hand to provide care with the aid of various toys and distraction techniques. All patients requiring anesthesia have a pre-anesthesia evaluation prior to sedation. Anesthetic risks for the procedure with regard to the current cardiopulmonary, neurological, endocrine and immune status of the patient are assessed. The risk of airway compromise and previous and current chemotherapy regimens are also assessed. Bearing in mind that a change in airway management may alter the radiation treatment plan and also require re-simulation, several factors were taken into consideration in the decision to use an unprotected airway. The decision to use an unprotected airway was based on an adequate cardiopulmonary status, the absence of obstructive airway lesions, and the ability of the patient to adequately clear oropharyngeal secretions when awake. A history of obstructive sleep apnea was a contraindication to non-invasive airway management. Prone positioning and radiation to the head and neck area did not serve as a contraindication to unprotected airway management. The appropriateness of non-invasive airway management was continuously assessed over the duration of treatment. Close collaboration and communication with the primary care team is essential to ensure uninterrupted chemo and radiotherapy sessions and also to acquire updates on the patients’ condition. Despite the majority of our patients being American Society of Anesthesiologists (ASA) risk class 3 or higher, all patients referred for anesthesia evaluation were allowed to undergo treatment under
anesthesia. None were referred for alternate methods of care based on anesthetic concerns. Fasting instructions according to the current ASA guidelines were provided. This typically requires no solids by mouth for 8 h, 6 h for milk and 4 h for breast milk. Clear fluid intake was encouraged for up to 2 h prior to treatment. An effort was made to treat younger children earlier in the day, since they are more prone to dehydration and less tolerable of the fasting guidelines. In general, each patient undergoes a simulation first followed by 10–33 daily proton treatments given Monday to Friday, each requiring sedation. Each session can last between 30 and 90 min depending on the complexity of the treatment set up and delivery. Patients who do not have central venous access were referred for surgical placement of such a line before the start of treatment. The majority of our patients are treated on an out-patient basis, and not routinely admitted to the hospital for post anesthetic or post radiotherapy care. In the absence of specific contraindications or airway concerns, induction of anesthesia and access of central lines is carried out on the treatment table (or computed tomography simulator suite) with the patient awake and seated on the parent’s lap. Due to the immunocompromised status of many patients central line access and handling was performed with strict sterile precautions. A child life specialist was present during induction and central line access to distract and comfort the child with toys and video games. Standard ASA monitors (electrocardiography, pulse oximetry, noninvasive blood pressure, and capnography) were placed. Our anesthetic management of choice is Total Intravenous Anesthesia with the patient spontaneously breathing. The induction and maintenance drug of choice is propofol. Induction and maintenance doses of propofol were titrated to individual patient requirements. Dexmedetomidine or narcotics were added when there was excessive patient movement despite higher than average doses of propofol. The depth of anesthesia was guided by hemodynamic parameters and the extent of patient movement during positioning. Bispectral Index monitoring of the depth of anesthesia is not utilized since the probe may interfere with the treatment field. Anti-emetics were routinely administered after induction. Thermoplastic immobilization masks are placed after an appropriate depth of anesthesia is established and supplemental oxygen was administered by nasal cannula or facemask. At the time of simulation, thermoplastic masks were fabricated in such a way as to elevate the patient’s chin, thereby promoting an open airway. During molding of the mask, orifices for placement of a nasal cannula are created. Alternatively, following fabrication of the mask, small sections are removed to allow for cannula placement, while respecting mask integrity. For treatments sessions, patients were secured to the treatment table with the aid of straps across their body and covered with a warm blanket. Cameras are positioned to allow visualization of the patient as well as monitors from the treatment control room. After the completion of treatment patients were transported to the recovery area staffed by a trained recovery room nurse. Standard monitoring was continued until the patient was awake, alert, hemodynamically stable, and tolerating oral intake if desired. Duration of stay in the recovery area was variable since most children were allowed to wake up spontaneously and feed in the recovery room. The staff anesthesiologist remained at the treatment facility until the last patient is discharged from the recovery area. Radiotherapy and chemotherapy specific anesthetic concerns A significant number of children receiving radiotherapy may have or be receiving concurrent chemotherapy. In addition to the well documented side effects of chemotherapy, gastrointestinal (GI) and hematologic toxicities are may be encountered during
Please cite this article in press as: Owusu-Agyemang P et al. Non-invasive anesthesia for children undergoing proton radiation therapy. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.01.016
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P. Owusu-Agyemang et al. / Radiotherapy and Oncology xxx (2014) xxx–xxx
the course of proton radiotherapy [10]. These toxicities may lead to interruptions or cancelations of treatment when not managed appropriately. Significant GI toxicity including nausea/vomiting, anorexia and dysphagia, may result in significant weight loss and adequate intravenous hydration during treatment is therefore essential. At our center, every effort is made to administer a 20 ml/kg bolus of normal saline followed by a maintenance rate. Fluid administration is continued in the recovery room if the bolus is not completed before the end of the treatment session. An antiemetic is also routinely administered during induction of anesthesia, and oral intake is encouraged before discharge from the recovery room. Radiation induced bone marrow damage during craniospinal irradiation may result in neutropenia and thrombocytopenia leading to an increased risk of infections and/or bleeding. At our center, central-line access and care is carried out with strict sterile precautions, and aggressive suctioning of oropharyngeal secretions is carried out to reduce the risk of pulmonary infections. Suctioning of the nasopharyngeal passages is avoided in the presence of thrombocytopenia. Chemotherapy induced cardiotoxictity is also well documented [11]. It is therefore imperative that the anesthesiologist is aware of the child’s chemotherapeutic regimen and its associated side effects. Induction and maintenance of anesthesia with propofol is slowly titrated so as not to decrease the mean blood pressure below 20% of baseline. Some movement of the patient is tolerated while immobilization masks are being placed. Adjuncts such as narcotics or dexmedetomidine are added when there is significant movement. Close monitoring of blood pressure is essential and non-invasive blood pressure measurements are carried out every 3 min.
Statistical analysis Descriptive statistics were used to summarize patient and clinical characteristics of interest. Results Between January 2006 and April 2013, 9328 anesthetics were administered to 340 unique children for the purposes of simulation and/or proton treatment. Patient characteristics and diagnoses are reported in Table 1. Two hundred and eight children (61%) had previous chemotherapy, and 110 (32%) children were receiving concurrent chemotherapy during proton therapy. Twelve patients underwent simulation but did not ultimately receive proton therapy. The majority of patients were treated for brain tumors and 39% received comprehensive radiation to the entire neural axis. Sites of irradiation are shown in Table 2. The median number of anesthetics including simulations and re-treatments was 31 (range, 1–61). The median total time under anesthesia for the entire treatment course was 20.3 h (range, 22 min to 40.2 h) with a median daily anesthesia time of 47 min (range, 15–79 min). The average time between start of anesthesia to the start of radiotherapy was 7.2 min (range, 1–83 min). For simulation without central venous access, 28 inhalation inductions (0.3%) were carried out for the purposes of peripheral intravenous line (IV) placement. All of these were followed by TIVA with propofol after an IV had been established. TIVA with spontaneous ventilation was employed in all patients. Three hundred and thirty three patients (97.9%) received propofol alone as the main induction and maintenance anesthetic. Seven patients (2.1%) required supplementation of their propofol anesthetic with dexmedetomidine. At first anesthetic session, the mean induction propofol dose was 4.1 mg/kg (range, 0.5–21.4).
Table 1 Patient characteristics and diagnoses. N = 340 (%)* Gender Male Female Age at consent, years Mean ± SD Median (min–max) Age at consent categorized Less than 1 year 1–3 years 4–10 years 11–14 years Weight (kg) Mean ± SD Median (min–max) Diagnosis Medulloblastoma Ependymoma Rhabdomyosarcoma Atypical teratoid rhabdoid tumor Primitive neuroectodermal tumor Retinoblastoma Astrocytoma Ewings sarcoma Neuroblastoma Craniopharyngioma Choroid plexus carcinoma Germ cell tumor Glioma Ganglioma Acute lymphoblastic Leukemia Other**
188 (55.3) 152 (44.7) 4.0 ± 2.4 3.6 (0.4–14.2) 17 (5.0) 176 (51.8) 141 (41.4) 6 (1.8) 17.4 ± 9.6 15.2 (2.8–109.0) 87 (25.6) 49 (14.4) 46 (13.5) 26 (7.6) 22 (6.4) 17 (5.0) 13 (3.8) 12 (3.5) 9 (2.6) 7 (2.1) 7 (2.1) 6 (1.8) 6 (1.8) 4 (1.2) 3 (0.9) 26 (7.6)
*
Percentages may not total 100 due to round-off error. Other includes: medulloepithelioma (2 patients); glioblastoma (2 patients); chondrosarcoma (2 patients); Only one patient was associated with each of the following diagnoses: astroblastoma; blue cell tumor, chest wall mass, germinoma, glioneuronal tumor, hepatoblastoma, leptomeningeal disease, acute myeloblastic leukemia, neurofibroma, osteoblastoma, osteosarcoma, spindle cell sarcoma, synovial sarcoma, teratoma, ameloblastic carcinoma, frontal sarcoma, orbial sarcoma, pineoblastoma, xanthoastocytoma.
**
Table 2 Sites of irradiation. N (%)* Sites of irradiation Craniospinal Brain Orbit Head and neck Pelvis Abdomen ace Thorax Other**
130 (39.8) 121 (37.0) 22 (6.7) 20 (6.1) 18 (5.5) 5 (1.5) 2 (0.6) 2 (0.6) 7 (2.1)
*
Percentages may not total 100 due to round-off error. Other includes only one patient associated with each of the following sites: paraspinal region, neck, perineum, sacrum, adrenal region, skull, and tibia.
**
Mean maintenance dose of propofol administered during the first treatment was 214.8 mcg/kg/min (range, 75–350). The antiemetics; ondanseteron or granisetron were administered routinely unless contraindicated or when the patient had received a dose prior to their proton therapy treatment. Narcotics were not administered routinely. Fentanyl, morphine or hydromorphone was administered 84 times (0.9%) to 36 unique patients. Bronchodilators were administered during 27 anesthetics (0.23%) to 13 unique patients (3.82%).
Please cite this article in press as: Owusu-Agyemang P et al. Non-invasive anesthesia for children undergoing proton radiation therapy. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.01.016
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Anesthesia for pediatric proton radiotherapy
Table 3 Patients requiring bronchodilator therapy. Patient
Age
Number sessions requiring bronchodilators
Anesthetic
Airway
Diagnosis
Site of irradiation
Notable events
1 2
1.3 6.6
1 1
NC NC
Rhabdomyosarcoma Craniopharyngioma
Neck Brain
Congested
3 4 5
4.4 1.3 1.6
1 1 6
NC NC NC/facemask
Retinoblastoma Retinoblastoma Orbit sarcoma
Orbit Orbit Orbit
6
1.1
5
Propofol Propofol/ dexmedetomidine Propofol Propofol Propofol/ dexmedetomidine Propofol
NC
Rhabdomyosarcoma
Orbit
7 8 9 10 11 12 13
7.8 2.4 2.4 2.2 2.8 2.2 7.5
3 1 1 2 1 3 1
Propofol Propofol Propofol Propofol Propofol Propofol Propofol
NC NC NC NC NC NC NC
Ependymoma Small round blue cell tumor Retinoblastoma Rhabdomyosarcoma Medulloepithelioma PNET Germ cell tumor
Brain Brain Orbit Nasopharynx Brain Brain Brain
All but 3 patients were treated in the supine position. A total of 9 patients had preexisting tracheostomies. Two patients required daily placement of a Laryngeal Mask Airway (LMA): one due to excess secretions and need for repeated suctioning and the second due to airway obstruction resulting from the head position in the immobilization mask. For the purposes of radiation simulation and treatment, no patient underwent endotracheal tube placement. Rather supplemental oxygen was delivered by nasal cannula or facemask in 96.7% of the patients. Five events qualified as major complications according to our definition. One child, with a history of diabetes insipidus and previous seizures, developed seizure activity during treatment and required on site intubation and was then transported to the main hospital by ambulance. This child recovered and continued proton therapy treatments within several days. This was the only admission to the hospital for complications occurring during anesthesia. There was one documented episode of bronchospasm, but several incidences of bronchodilator use (27 events, or 0.23% of total anesthetics). Table 3 shows the characteristics of the children (n = 13) and events requiring bronchodilator therapy. Two patients required atropine for bradycardia resulting from desaturation. There was one documented episode of laryngospasm, which was treated with positive pressure ventilation. No patients required CPR or the administration of epinephrine. There were no documented episodes of pulmonary aspiration or airway complications requiring intubation or the administration of succinylcholine. Discussion The stand-alone nature of many proton therapy centers presents a specific challenge to the anesthesia provider due to the lack of back up, and absence of onsite laboratory facilities, etc. However, the current study provides support for the safety of propofol based anesthesia and non-invasive airway management during sedation at such treatment centers. The importance of a dedicated sedation team in reducing anesthesia related complications is well-documented [12]. At our institution, a select team of anesthesiologists and CRNAs has been formed to staff the proton therapy center. This has led to familiarity with the anesthesia setup and the location of various supplies. Children become accustomed to the familiar faces, which greatly reduces their level of anxiety. Distraction techniques have been shown to be effective in reducing the perception of pain and levels of anxiety in children undergoing invasive and noninvasive procedures [13,14]. More recently electronic-based distraction techniques, now employed at our center, have also been shown to be effective [15,16].
Copious secretions, tight mask fit, re-simulated Current URI Secretions, suctioned Bronchospasm
Various anesthetic techniques are utilized for conventional and proton radiation therapy. They include general inhalational anesthesia with endotracheal intubation and deep sedation with midazolam, ketamine, meperidine, dexmedetomidine or propofol [1,3–5]. Our anesthetic of choice is TIVA with propofol, which has been shown to be safe and effective for children undergoing complex imaging and radiation therapy [9,17]. The risk of aspiration, central apnea and airway obstruction during delivery of anesthesia outside the operating room is well-documented [18,19]. It is therefore not surprising that some institutions choose to employ general anesthesia with endotracheal intubation or LMA placement as the preferred method of anesthesia delivery during proton therapy [20]. In our series of over 9300 propofol anesthetics with a nasal cannula or facemask, there were no airway or pulmonary complications requiring intubation or the administration of succinylcholine. However, there was one documented episode of laryngospasm (0.01%), one episode of bronchospasm (0.01%) and 2 episodes of atropine administration for bradycardia secondary to desaturation (0.02%). the incidence of major airway complications (0.04%) reported here is comparable to the 0.05% incidence reported by Buchsbaum et al. in their review of anesthetic complications during proton radiation therapy when patients were intubated [20]. Also, our incidences of laryngospasm (0.01%), pulmonary aspiration (0%), and unexpected admission to the hospital (0.01%) were lower than the reported incidences of 0.5%, 0.008%, and 0.07%, respectively in a large database review of adverse events during pediatric sedation with propofol outside the operating room [18]. Although the reasons or thresholds for bronchodilator administration were unclear on many occasions, it may be safe to conclude that children who required frequent suctioning and bronchodilator treatments may not have been good candidates for anesthesia with an unprotected airway. Apart from the increased risk or bronchospasm and laryngospasm in this group of patients, frequent suctioning and bronchodilator administration may result in several interruptions of treatments, as well as prolonged treatment times. X-ray imaging obtained as part of image guided radiotherapy, which is employed for all proton patients, may also need to be re-taken to confirm adequate positioning thereby resulting in increased radiation exposure as well as additional in room time. Regardless, our results suggest that careful patient selection may allow TIVA with a facemask or nasal cannula to be safely employed during proton therapy, thus avoiding daily intubations [5,21]. A lower aggregate dose of propofol may be necessary when airway instrumentation is not required, and may lead to a quicker recovery from anesthesia. Our single direct admission to the hospital for seizure activity has reinforced the importance of updates on
Please cite this article in press as: Owusu-Agyemang P et al. Non-invasive anesthesia for children undergoing proton radiation therapy. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.01.016
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our patients’ condition over the course of treatment, and to follow up on pertinent laboratory tests. Children undergoing proton radiation therapy may have received or be receiving chemotherapy, making them prone to neutropenia, and therefore infections. Central line access and drug administration should therefore be done with particular attention to sterility. Though the risk of nausea and vomiting due to craniospinal radiotherapy is reduced with proton therapy, it may still occur in 40% of the patients [22]. We therefore routinely administer anti-emetics to all our patients receiving craniospinal irradiation. In regard to patient setup as part of the proton therapy planning and delivery, the vast majority of our patients were treated in the supine position, which facilitates airway access by the anesthesia team. In our experience, one key to successful, un-interrupted completion of treatments is to have an immobilization mask fit that will not compromise the airway as treatment progresses. In order to achieve this, the anesthesiologist must participate in the immobilization mask molding process to ensure there is appropriate neck extension and/or jaw thrust to optimize airway patency. The latter practice has reduced the number of patients with airway obstruction during treatment and the need for re-simulations at our institution. It is important that the anesthesia team and the radiation therapy team work in unison to ensure the safety of the patient. During treatments, radiation therapists may need to adjust the child’s position to match the simulation set up to allow precise targeting according to the calculated radiation plan. The radiation therapist may occasionally remove the immobilization mask in order to reposition the head. It is therefore important that members of the anesthesia team be aware of the intentions of the therapists at various times during the treatment. Another example is for the anesthesia team to be aware of the treatment room layout. Activation of movement and pressure sensors around the treatment gantry may also result in the interruption of treatment. Monitoring cables and intravenous lines have to be secured away from these sensors. Conclusion Our review of over 9300 anesthetics demonstrates that anesthesia providers with pediatric anesthesia expertise may safely anesthetize children undergoing proton radiation therapy. Coordination and communication with all members of the healthcare team is essential to ensure the safety of the treatment process, and leads to a better understanding of anesthesia related issues. Careful patient selection along with fabrication of immobilization masks which will not compromise the airway allows the use of propofol TIVA with spontaneous ventilation and oxygen delivery by face mask or nasal cannula, thereby avoiding repeated intubations.
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References [1] Seiler G, De Vol E, Khafaga Y, et al. Evaluation of the safety and efficacy of repeated sedations for the radiotherapy of young children with cancer: a prospective study of 1033 consecutive sedations. Int J Radiat Oncol Biol Phys 2001;49:771–83. [2] Scheiber G, Ribeiro FC, Karpienski H, et al. Deep sedation with propofol in preschool children undergoing radiation therapy. Paediatr Anaesth 1996;6:209–13. [3] Wojcieszek E, Rembielak A, Bialas B, et al. Anaesthesia for radiation therapy – Gliwice experience. Neoplasma 2010;57:155–60. [4] Shukry M, Ramadhyani U. Dexmedetomidine as the primary sedative agent for brain radiation therapy in a 21-month old child. Pediatr Anesth 2005;15:241–2. [5] Anghelescu DL, Burgoyne LL, Liu W, et al. Safe anesthesia for radiotherapy in pediatric oncology: St. Jude Children’s Research Hospital Experience, 2004– 2006. Int J Radiat Oncol Biol Phys 2008;71:491–7. [6] McFadyen JG, Pelly N, Orr RJ. Sedation and anesthesia for the pediatric patient undergoing radiation therapy. Curr Opin Anaesthesiol 2011;24:433–8. doi: 410.1097/ACO.1090b1013e328347f328931. [7] Buchsbaum JC, McMullen KP, Douglas JG, et al. Repetitive pediatric anesthesia in a non-hospital setting. Int J Radiat Oncol Biol Phys 2013;85:1296–300. doi: 1210.1016/j.ijrobp.2012.1210.1006. Epub 2012 Dec 1291. [8] Weiss M, Frei M, Buehrer S, et al. Deep propofol sedation for vacuum-assisted bite-block immobilization in children undergoing proton radiation therapy of cranial tumors. Paediatr Anaesth 2007;17:867–73. [9] Buehrer S, Immoos S, Frei M, et al. Evaluation of propofol for repeated prolonged deep sedation in children undergoing proton radiation therapy. Br J Anaesth 2007;99:556–60. [10] Brown AP, Barney CL, Grosshans DR, et al. Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol Biol Phys 2013;86:277–84. [11] Ai D, Banchs J, Owusu-Agyemang P, et al. Chemotherapy induced cardiovascular toxicity: beyond anthracyclines. Minerva Anestesiol. 2013 Oct 14. [Epub ahead of print]. [12] Gozal D, Drenger B, Levin PD, et al. A pediatric sedation/anesthesia program with dedicated care by anesthesiologists and nurses for procedures outside the operating room. J Pediatr 2004;145:47–52. [13] Chambers CT, Taddio A, Uman LS, et al. Psychological interventions for reducing pain and distress during routine childhood immunizations: a systematic review. Clin Therapeut 2009;31:S77–S103. [14] Yip P, Middleton P, Cyna AM, et al. Non-pharmacological interventions for assisting the induction of anaesthesia in children. Cochr Database Systemat Rev 2009;3:CD006447. [15] Patel A, Schieble T, Davidson M, et al. Distraction with a hand-held video game reduces pediatric preoperative anxiety. Paediatr Anaesth 2006;16:1019–27. [16] McQueen A, Cress C, Tothy A. Using a tablet computer during pediatric procedures a case series and review of the ‘‘apps’’. Pediatr Emerg Care 2012;28:712–4. [17] Griffiths MA, Kamat PP, McCracken CE, et al. Is procedural sedation with propofol acceptable for complex imaging? A comparison of short vs. prolonged sedations in children. Pediatr Radiol 2013. [18] Cravero JP, Beach ML, Blike GT, et al. The incidence and nature of adverse events during pediatric sedation/anesthesia with propofol for procedures outside the operating room: a report from the Pediatric Sedation Research Consortium. Anesth Analg 2009;108:795–804. [19] Stokes MA, Soriano SG, Tarbell NJ, et al. Anesthesia for stereotactic radiosurgery in children. J Neurosurg Anesthesiol 1995;7:100–8. [20] Buchsbaum JC, McMullen KP, Douglas JG, et al. Repetitive pediatric anesthesia in a non-hospital setting. Int J Radiat Oncol Biol Phys 2013;85:1296–300. [21] McFadyen JG, Pelly N, Orr RJ. Sedation and anesthesia for the pediatric patient undergoing radiation therapy. Curr Opin Anaesthesiol 2011;24:433–8. [22] Suneja G, Poorvu PD, Hill-Kayser C, et al. Acute toxicity of proton beam radiation for pediatric central nervous system malignancies. Pediatr Blood Cancer 2013.
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Radiotherapy and Oncology journal homepage: www.thegreenjournal.com
Original article
Non-invasive anesthesia for children undergoing proton radiation therapy Pascal Owusu-Agyemang a,⇑, David Grosshans b, Radha Arunkumar a, Elizabeth Rebello a, Shannon Popovich a, Acsa Zavala a, Cynthia Williams a, Javier Ruiz a, Mike Hernandez c, Anita Mahajan b,1, Vivian Porche a,1 a Department of Anesthesiology & Perioperative Medicine; b Department of Radiation Oncology; c Department of Biostatistics, The University of Texas MD Anderson Cancer Center, United States
a r t i c l e
i n f o
Article history: Received 28 November 2013 Received in revised form 21 January 2014 Accepted 21 January 2014 Available online xxxx Keywords: Anesthesia Children Proton radiotherapy
a b s t r a c t Background: Proton therapy is a newer modality of radiotherapy during which anesthesiologists face specific challenges related to the setup and duration of treatment sessions. Purpose: Describe our anesthesia practice for children treated in a standalone proton therapy center, and report on complications encountered during anesthesia. Materials and methods: A retrospective review of anesthetic records for patients 618 years of age treated with proton therapy at our institution between January 2006 and April 2013 was performed. Results: A total of 9328 anesthetics were administered to 340 children with a median age of 3.6 years (range, 0.4–14.2). The median daily anesthesia time was 47 min (range, 15–79). The average time between start of anesthesia to the start of radiotherapy was 7.2 min (range, 1–83 min). All patients received Total Intravenous Anesthesia (TIVA) with spontaneous ventilation, with 96.7% receiving supplemental oxygen by non-invasive methods. None required daily endotracheal intubation. Two episodes of bradycardia, and one episode each of; seizure, laryngospasm and bronchospasm were identified for a cumulative incidence of 0.05%. Conclusions: In this large series of children undergoing proton therapy at a freestanding center, TIVA without daily endotracheal intubation provided a safe, efficient, and less invasive option of anesthetic care. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2014) xxx–xxx
Proton therapy is a radiation modality gaining increasing popularity, particularly for the treatment of pediatric cancer patients. Particle therapy, including proton therapy has unique physical properties, which allow for the reduction or elimination of unnecessary dose to normal tissues. It is believed that reduced normal tissue exposure will translate into both decreased rates of both early and late treatment induced toxicities. As such, increasingly young patients are commonly referred, many of who require anesthesia given the need for prolonged immobilization with treatment sessions ranging from 30 to 90 min in length. Several authors have described techniques for anesthetizing children undergoing conventional radiation therapy [1–6]. Anesthesia for proton therapy is unique due to the specific patient set up requirements and potentially longer duration of individual treatments. Moreover, currently the majority of proton therapy ⇑ Corresponding author. Address: Department of Anesthesiology & Perioperative Medicine, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 0409, Houston, TX 77030, United States. E-mail address: [email protected] (P. Owusu-Agyemang). 1 These authors contributed equally.
centers are not within inpatient facilities and as such the capacity for emergency response is limited. There are a limited number of publications on the safety and techniques of providing anesthesia for proton therapy. Investigators from the Indiana University Health Proton center have described their initial experience, recording a low rate of anesthetic related complications at their offsite facility [7]. In their report, anesthesia was induced, a laryngeal mask airway (LMA) placed and anesthesia maintained using inhalational sevoflurane [7]. In contrast, investigators from the University’s Children Hospital and the Paul Scherrer Institute in Switzerland reported on the use of propofol sedation in 10 pediatric patients treated with proton therapy without placement of an artificial airway [8,9]. Such an approach avoids repeated daily instrument-induced irritation of the airway and facilitates immobilization with thermoplastic masks. Additional benefits of avoiding artificial airways may include a reduction in the total amount of anesthetic necessary to maintain adequate sedation and decreased overall room time. As new proton centers continue to emerge, there is a need for further publications describing the anesthetic management for
http://dx.doi.org/10.1016/j.radonc.2014.01.016 0167-8140/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Owusu-Agyemang P et al. Non-invasive anesthesia for children undergoing proton radiation therapy. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.01.016
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Anesthesia for pediatric proton radiotherapy
children undergoing proton therapy. The primary objective of our study was to review and describe the anesthetic management of children undergoing proton radiation therapy at our center and report on anesthesia-related complications. Materials and methods After approval by the University of Texas MD Anderson Cancer Center Institutional Review Board, we retrospectively reviewed the records of children 18 years of age and younger treated with proton therapy between September 2006 and April 2013. Patient demographics, medical history, site of irradiation, number of anesthetic sessions and route of administration were recorded. Airway management, medications administered, duration of anesthetics, and major complications occurring during anesthesia were recorded. Major complications were defined as the following: cardiopulmonary resuscitation, urgent intubation, unexpected admission to the hospital, the administration of epinephrine or atropine, laryngospasm, pulmonary aspiration, and bronchospasm. Coughing, which required suctioning, and brief spells of apnea or desaturation were not classified as major complications. Likewise, episodes of hypotension or bradycardia, which did not require the administration of epinephrine or atropine, were not classified as major complications. Anesthetic personnel and patient management The proton therapy center is a standalone facility located one mile from the main MD Anderson Hospital Campus. The anesthesia team consists of a physician with pediatric anesthesia expertise and a Certified Registered Nurse Anesthetist (CRNA). Other medical personnel at the facility include; radiation oncologists, radiation therapists, and registered nurses. Referrals for proton therapy under anesthesia are based on the age of the patient, prior history of requiring anesthesia for imaging, the emotional maturity of the child, and the duration and site of treatment. We treat a number of international patients at our proton therapy center, and we have noted anecdotally that European patients above the age of 5 years often do not require anesthesia. It is however not uncommon for North American children over the age of 7 to undergo these procedures under anesthesia. In the event that anesthesia is not required, child life specialists are on hand to provide care with the aid of various toys and distraction techniques. All patients requiring anesthesia have a pre-anesthesia evaluation prior to sedation. Anesthetic risks for the procedure with regard to the current cardiopulmonary, neurological, endocrine and immune status of the patient are assessed. The risk of airway compromise and previous and current chemotherapy regimens are also assessed. Bearing in mind that a change in airway management may alter the radiation treatment plan and also require re-simulation, several factors were taken into consideration in the decision to use an unprotected airway. The decision to use an unprotected airway was based on an adequate cardiopulmonary status, the absence of obstructive airway lesions, and the ability of the patient to adequately clear oropharyngeal secretions when awake. A history of obstructive sleep apnea was a contraindication to non-invasive airway management. Prone positioning and radiation to the head and neck area did not serve as a contraindication to unprotected airway management. The appropriateness of non-invasive airway management was continuously assessed over the duration of treatment. Close collaboration and communication with the primary care team is essential to ensure uninterrupted chemo and radiotherapy sessions and also to acquire updates on the patients’ condition. Despite the majority of our patients being American Society of Anesthesiologists (ASA) risk class 3 or higher, all patients referred for anesthesia evaluation were allowed to undergo treatment under
anesthesia. None were referred for alternate methods of care based on anesthetic concerns. Fasting instructions according to the current ASA guidelines were provided. This typically requires no solids by mouth for 8 h, 6 h for milk and 4 h for breast milk. Clear fluid intake was encouraged for up to 2 h prior to treatment. An effort was made to treat younger children earlier in the day, since they are more prone to dehydration and less tolerable of the fasting guidelines. In general, each patient undergoes a simulation first followed by 10–33 daily proton treatments given Monday to Friday, each requiring sedation. Each session can last between 30 and 90 min depending on the complexity of the treatment set up and delivery. Patients who do not have central venous access were referred for surgical placement of such a line before the start of treatment. The majority of our patients are treated on an out-patient basis, and not routinely admitted to the hospital for post anesthetic or post radiotherapy care. In the absence of specific contraindications or airway concerns, induction of anesthesia and access of central lines is carried out on the treatment table (or computed tomography simulator suite) with the patient awake and seated on the parent’s lap. Due to the immunocompromised status of many patients central line access and handling was performed with strict sterile precautions. A child life specialist was present during induction and central line access to distract and comfort the child with toys and video games. Standard ASA monitors (electrocardiography, pulse oximetry, noninvasive blood pressure, and capnography) were placed. Our anesthetic management of choice is Total Intravenous Anesthesia with the patient spontaneously breathing. The induction and maintenance drug of choice is propofol. Induction and maintenance doses of propofol were titrated to individual patient requirements. Dexmedetomidine or narcotics were added when there was excessive patient movement despite higher than average doses of propofol. The depth of anesthesia was guided by hemodynamic parameters and the extent of patient movement during positioning. Bispectral Index monitoring of the depth of anesthesia is not utilized since the probe may interfere with the treatment field. Anti-emetics were routinely administered after induction. Thermoplastic immobilization masks are placed after an appropriate depth of anesthesia is established and supplemental oxygen was administered by nasal cannula or facemask. At the time of simulation, thermoplastic masks were fabricated in such a way as to elevate the patient’s chin, thereby promoting an open airway. During molding of the mask, orifices for placement of a nasal cannula are created. Alternatively, following fabrication of the mask, small sections are removed to allow for cannula placement, while respecting mask integrity. For treatments sessions, patients were secured to the treatment table with the aid of straps across their body and covered with a warm blanket. Cameras are positioned to allow visualization of the patient as well as monitors from the treatment control room. After the completion of treatment patients were transported to the recovery area staffed by a trained recovery room nurse. Standard monitoring was continued until the patient was awake, alert, hemodynamically stable, and tolerating oral intake if desired. Duration of stay in the recovery area was variable since most children were allowed to wake up spontaneously and feed in the recovery room. The staff anesthesiologist remained at the treatment facility until the last patient is discharged from the recovery area. Radiotherapy and chemotherapy specific anesthetic concerns A significant number of children receiving radiotherapy may have or be receiving concurrent chemotherapy. In addition to the well documented side effects of chemotherapy, gastrointestinal (GI) and hematologic toxicities are may be encountered during
Please cite this article in press as: Owusu-Agyemang P et al. Non-invasive anesthesia for children undergoing proton radiation therapy. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.01.016
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the course of proton radiotherapy [10]. These toxicities may lead to interruptions or cancelations of treatment when not managed appropriately. Significant GI toxicity including nausea/vomiting, anorexia and dysphagia, may result in significant weight loss and adequate intravenous hydration during treatment is therefore essential. At our center, every effort is made to administer a 20 ml/kg bolus of normal saline followed by a maintenance rate. Fluid administration is continued in the recovery room if the bolus is not completed before the end of the treatment session. An antiemetic is also routinely administered during induction of anesthesia, and oral intake is encouraged before discharge from the recovery room. Radiation induced bone marrow damage during craniospinal irradiation may result in neutropenia and thrombocytopenia leading to an increased risk of infections and/or bleeding. At our center, central-line access and care is carried out with strict sterile precautions, and aggressive suctioning of oropharyngeal secretions is carried out to reduce the risk of pulmonary infections. Suctioning of the nasopharyngeal passages is avoided in the presence of thrombocytopenia. Chemotherapy induced cardiotoxictity is also well documented [11]. It is therefore imperative that the anesthesiologist is aware of the child’s chemotherapeutic regimen and its associated side effects. Induction and maintenance of anesthesia with propofol is slowly titrated so as not to decrease the mean blood pressure below 20% of baseline. Some movement of the patient is tolerated while immobilization masks are being placed. Adjuncts such as narcotics or dexmedetomidine are added when there is significant movement. Close monitoring of blood pressure is essential and non-invasive blood pressure measurements are carried out every 3 min.
Statistical analysis Descriptive statistics were used to summarize patient and clinical characteristics of interest. Results Between January 2006 and April 2013, 9328 anesthetics were administered to 340 unique children for the purposes of simulation and/or proton treatment. Patient characteristics and diagnoses are reported in Table 1. Two hundred and eight children (61%) had previous chemotherapy, and 110 (32%) children were receiving concurrent chemotherapy during proton therapy. Twelve patients underwent simulation but did not ultimately receive proton therapy. The majority of patients were treated for brain tumors and 39% received comprehensive radiation to the entire neural axis. Sites of irradiation are shown in Table 2. The median number of anesthetics including simulations and re-treatments was 31 (range, 1–61). The median total time under anesthesia for the entire treatment course was 20.3 h (range, 22 min to 40.2 h) with a median daily anesthesia time of 47 min (range, 15–79 min). The average time between start of anesthesia to the start of radiotherapy was 7.2 min (range, 1–83 min). For simulation without central venous access, 28 inhalation inductions (0.3%) were carried out for the purposes of peripheral intravenous line (IV) placement. All of these were followed by TIVA with propofol after an IV had been established. TIVA with spontaneous ventilation was employed in all patients. Three hundred and thirty three patients (97.9%) received propofol alone as the main induction and maintenance anesthetic. Seven patients (2.1%) required supplementation of their propofol anesthetic with dexmedetomidine. At first anesthetic session, the mean induction propofol dose was 4.1 mg/kg (range, 0.5–21.4).
Table 1 Patient characteristics and diagnoses. N = 340 (%)* Gender Male Female Age at consent, years Mean ± SD Median (min–max) Age at consent categorized Less than 1 year 1–3 years 4–10 years 11–14 years Weight (kg) Mean ± SD Median (min–max) Diagnosis Medulloblastoma Ependymoma Rhabdomyosarcoma Atypical teratoid rhabdoid tumor Primitive neuroectodermal tumor Retinoblastoma Astrocytoma Ewings sarcoma Neuroblastoma Craniopharyngioma Choroid plexus carcinoma Germ cell tumor Glioma Ganglioma Acute lymphoblastic Leukemia Other**
188 (55.3) 152 (44.7) 4.0 ± 2.4 3.6 (0.4–14.2) 17 (5.0) 176 (51.8) 141 (41.4) 6 (1.8) 17.4 ± 9.6 15.2 (2.8–109.0) 87 (25.6) 49 (14.4) 46 (13.5) 26 (7.6) 22 (6.4) 17 (5.0) 13 (3.8) 12 (3.5) 9 (2.6) 7 (2.1) 7 (2.1) 6 (1.8) 6 (1.8) 4 (1.2) 3 (0.9) 26 (7.6)
*
Percentages may not total 100 due to round-off error. Other includes: medulloepithelioma (2 patients); glioblastoma (2 patients); chondrosarcoma (2 patients); Only one patient was associated with each of the following diagnoses: astroblastoma; blue cell tumor, chest wall mass, germinoma, glioneuronal tumor, hepatoblastoma, leptomeningeal disease, acute myeloblastic leukemia, neurofibroma, osteoblastoma, osteosarcoma, spindle cell sarcoma, synovial sarcoma, teratoma, ameloblastic carcinoma, frontal sarcoma, orbial sarcoma, pineoblastoma, xanthoastocytoma.
**
Table 2 Sites of irradiation. N (%)* Sites of irradiation Craniospinal Brain Orbit Head and neck Pelvis Abdomen ace Thorax Other**
130 (39.8) 121 (37.0) 22 (6.7) 20 (6.1) 18 (5.5) 5 (1.5) 2 (0.6) 2 (0.6) 7 (2.1)
*
Percentages may not total 100 due to round-off error. Other includes only one patient associated with each of the following sites: paraspinal region, neck, perineum, sacrum, adrenal region, skull, and tibia.
**
Mean maintenance dose of propofol administered during the first treatment was 214.8 mcg/kg/min (range, 75–350). The antiemetics; ondanseteron or granisetron were administered routinely unless contraindicated or when the patient had received a dose prior to their proton therapy treatment. Narcotics were not administered routinely. Fentanyl, morphine or hydromorphone was administered 84 times (0.9%) to 36 unique patients. Bronchodilators were administered during 27 anesthetics (0.23%) to 13 unique patients (3.82%).
Please cite this article in press as: Owusu-Agyemang P et al. Non-invasive anesthesia for children undergoing proton radiation therapy. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.01.016
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Anesthesia for pediatric proton radiotherapy
Table 3 Patients requiring bronchodilator therapy. Patient
Age
Number sessions requiring bronchodilators
Anesthetic
Airway
Diagnosis
Site of irradiation
Notable events
1 2
1.3 6.6
1 1
NC NC
Rhabdomyosarcoma Craniopharyngioma
Neck Brain
Congested
3 4 5
4.4 1.3 1.6
1 1 6
NC NC NC/facemask
Retinoblastoma Retinoblastoma Orbit sarcoma
Orbit Orbit Orbit
6
1.1
5
Propofol Propofol/ dexmedetomidine Propofol Propofol Propofol/ dexmedetomidine Propofol
NC
Rhabdomyosarcoma
Orbit
7 8 9 10 11 12 13
7.8 2.4 2.4 2.2 2.8 2.2 7.5
3 1 1 2 1 3 1
Propofol Propofol Propofol Propofol Propofol Propofol Propofol
NC NC NC NC NC NC NC
Ependymoma Small round blue cell tumor Retinoblastoma Rhabdomyosarcoma Medulloepithelioma PNET Germ cell tumor
Brain Brain Orbit Nasopharynx Brain Brain Brain
All but 3 patients were treated in the supine position. A total of 9 patients had preexisting tracheostomies. Two patients required daily placement of a Laryngeal Mask Airway (LMA): one due to excess secretions and need for repeated suctioning and the second due to airway obstruction resulting from the head position in the immobilization mask. For the purposes of radiation simulation and treatment, no patient underwent endotracheal tube placement. Rather supplemental oxygen was delivered by nasal cannula or facemask in 96.7% of the patients. Five events qualified as major complications according to our definition. One child, with a history of diabetes insipidus and previous seizures, developed seizure activity during treatment and required on site intubation and was then transported to the main hospital by ambulance. This child recovered and continued proton therapy treatments within several days. This was the only admission to the hospital for complications occurring during anesthesia. There was one documented episode of bronchospasm, but several incidences of bronchodilator use (27 events, or 0.23% of total anesthetics). Table 3 shows the characteristics of the children (n = 13) and events requiring bronchodilator therapy. Two patients required atropine for bradycardia resulting from desaturation. There was one documented episode of laryngospasm, which was treated with positive pressure ventilation. No patients required CPR or the administration of epinephrine. There were no documented episodes of pulmonary aspiration or airway complications requiring intubation or the administration of succinylcholine. Discussion The stand-alone nature of many proton therapy centers presents a specific challenge to the anesthesia provider due to the lack of back up, and absence of onsite laboratory facilities, etc. However, the current study provides support for the safety of propofol based anesthesia and non-invasive airway management during sedation at such treatment centers. The importance of a dedicated sedation team in reducing anesthesia related complications is well-documented [12]. At our institution, a select team of anesthesiologists and CRNAs has been formed to staff the proton therapy center. This has led to familiarity with the anesthesia setup and the location of various supplies. Children become accustomed to the familiar faces, which greatly reduces their level of anxiety. Distraction techniques have been shown to be effective in reducing the perception of pain and levels of anxiety in children undergoing invasive and noninvasive procedures [13,14]. More recently electronic-based distraction techniques, now employed at our center, have also been shown to be effective [15,16].
Copious secretions, tight mask fit, re-simulated Current URI Secretions, suctioned Bronchospasm
Various anesthetic techniques are utilized for conventional and proton radiation therapy. They include general inhalational anesthesia with endotracheal intubation and deep sedation with midazolam, ketamine, meperidine, dexmedetomidine or propofol [1,3–5]. Our anesthetic of choice is TIVA with propofol, which has been shown to be safe and effective for children undergoing complex imaging and radiation therapy [9,17]. The risk of aspiration, central apnea and airway obstruction during delivery of anesthesia outside the operating room is well-documented [18,19]. It is therefore not surprising that some institutions choose to employ general anesthesia with endotracheal intubation or LMA placement as the preferred method of anesthesia delivery during proton therapy [20]. In our series of over 9300 propofol anesthetics with a nasal cannula or facemask, there were no airway or pulmonary complications requiring intubation or the administration of succinylcholine. However, there was one documented episode of laryngospasm (0.01%), one episode of bronchospasm (0.01%) and 2 episodes of atropine administration for bradycardia secondary to desaturation (0.02%). the incidence of major airway complications (0.04%) reported here is comparable to the 0.05% incidence reported by Buchsbaum et al. in their review of anesthetic complications during proton radiation therapy when patients were intubated [20]. Also, our incidences of laryngospasm (0.01%), pulmonary aspiration (0%), and unexpected admission to the hospital (0.01%) were lower than the reported incidences of 0.5%, 0.008%, and 0.07%, respectively in a large database review of adverse events during pediatric sedation with propofol outside the operating room [18]. Although the reasons or thresholds for bronchodilator administration were unclear on many occasions, it may be safe to conclude that children who required frequent suctioning and bronchodilator treatments may not have been good candidates for anesthesia with an unprotected airway. Apart from the increased risk or bronchospasm and laryngospasm in this group of patients, frequent suctioning and bronchodilator administration may result in several interruptions of treatments, as well as prolonged treatment times. X-ray imaging obtained as part of image guided radiotherapy, which is employed for all proton patients, may also need to be re-taken to confirm adequate positioning thereby resulting in increased radiation exposure as well as additional in room time. Regardless, our results suggest that careful patient selection may allow TIVA with a facemask or nasal cannula to be safely employed during proton therapy, thus avoiding daily intubations [5,21]. A lower aggregate dose of propofol may be necessary when airway instrumentation is not required, and may lead to a quicker recovery from anesthesia. Our single direct admission to the hospital for seizure activity has reinforced the importance of updates on
Please cite this article in press as: Owusu-Agyemang P et al. Non-invasive anesthesia for children undergoing proton radiation therapy. Radiother Oncol (2014), http://dx.doi.org/10.1016/j.radonc.2014.01.016
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our patients’ condition over the course of treatment, and to follow up on pertinent laboratory tests. Children undergoing proton radiation therapy may have received or be receiving chemotherapy, making them prone to neutropenia, and therefore infections. Central line access and drug administration should therefore be done with particular attention to sterility. Though the risk of nausea and vomiting due to craniospinal radiotherapy is reduced with proton therapy, it may still occur in 40% of the patients [22]. We therefore routinely administer anti-emetics to all our patients receiving craniospinal irradiation. In regard to patient setup as part of the proton therapy planning and delivery, the vast majority of our patients were treated in the supine position, which facilitates airway access by the anesthesia team. In our experience, one key to successful, un-interrupted completion of treatments is to have an immobilization mask fit that will not compromise the airway as treatment progresses. In order to achieve this, the anesthesiologist must participate in the immobilization mask molding process to ensure there is appropriate neck extension and/or jaw thrust to optimize airway patency. The latter practice has reduced the number of patients with airway obstruction during treatment and the need for re-simulations at our institution. It is important that the anesthesia team and the radiation therapy team work in unison to ensure the safety of the patient. During treatments, radiation therapists may need to adjust the child’s position to match the simulation set up to allow precise targeting according to the calculated radiation plan. The radiation therapist may occasionally remove the immobilization mask in order to reposition the head. It is therefore important that members of the anesthesia team be aware of the intentions of the therapists at various times during the treatment. Another example is for the anesthesia team to be aware of the treatment room layout. Activation of movement and pressure sensors around the treatment gantry may also result in the interruption of treatment. Monitoring cables and intravenous lines have to be secured away from these sensors. Conclusion Our review of over 9300 anesthetics demonstrates that anesthesia providers with pediatric anesthesia expertise may safely anesthetize children undergoing proton radiation therapy. Coordination and communication with all members of the healthcare team is essential to ensure the safety of the treatment process, and leads to a better understanding of anesthesia related issues. Careful patient selection along with fabrication of immobilization masks which will not compromise the airway allows the use of propofol TIVA with spontaneous ventilation and oxygen delivery by face mask or nasal cannula, thereby avoiding repeated intubations.
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References [1] Seiler G, De Vol E, Khafaga Y, et al. Evaluation of the safety and efficacy of repeated sedations for the radiotherapy of young children with cancer: a prospective study of 1033 consecutive sedations. Int J Radiat Oncol Biol Phys 2001;49:771–83. [2] Scheiber G, Ribeiro FC, Karpienski H, et al. Deep sedation with propofol in preschool children undergoing radiation therapy. Paediatr Anaesth 1996;6:209–13. [3] Wojcieszek E, Rembielak A, Bialas B, et al. Anaesthesia for radiation therapy – Gliwice experience. Neoplasma 2010;57:155–60. [4] Shukry M, Ramadhyani U. Dexmedetomidine as the primary sedative agent for brain radiation therapy in a 21-month old child. Pediatr Anesth 2005;15:241–2. [5] Anghelescu DL, Burgoyne LL, Liu W, et al. Safe anesthesia for radiotherapy in pediatric oncology: St. Jude Children’s Research Hospital Experience, 2004– 2006. Int J Radiat Oncol Biol Phys 2008;71:491–7. [6] McFadyen JG, Pelly N, Orr RJ. Sedation and anesthesia for the pediatric patient undergoing radiation therapy. Curr Opin Anaesthesiol 2011;24:433–8. doi: 410.1097/ACO.1090b1013e328347f328931. [7] Buchsbaum JC, McMullen KP, Douglas JG, et al. Repetitive pediatric anesthesia in a non-hospital setting. Int J Radiat Oncol Biol Phys 2013;85:1296–300. doi: 1210.1016/j.ijrobp.2012.1210.1006. Epub 2012 Dec 1291. [8] Weiss M, Frei M, Buehrer S, et al. Deep propofol sedation for vacuum-assisted bite-block immobilization in children undergoing proton radiation therapy of cranial tumors. Paediatr Anaesth 2007;17:867–73. [9] Buehrer S, Immoos S, Frei M, et al. Evaluation of propofol for repeated prolonged deep sedation in children undergoing proton radiation therapy. Br J Anaesth 2007;99:556–60. [10] Brown AP, Barney CL, Grosshans DR, et al. Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol Biol Phys 2013;86:277–84. [11] Ai D, Banchs J, Owusu-Agyemang P, et al. Chemotherapy induced cardiovascular toxicity: beyond anthracyclines. Minerva Anestesiol. 2013 Oct 14. [Epub ahead of print]. [12] Gozal D, Drenger B, Levin PD, et al. A pediatric sedation/anesthesia program with dedicated care by anesthesiologists and nurses for procedures outside the operating room. J Pediatr 2004;145:47–52. [13] Chambers CT, Taddio A, Uman LS, et al. Psychological interventions for reducing pain and distress during routine childhood immunizations: a systematic review. Clin Therapeut 2009;31:S77–S103. [14] Yip P, Middleton P, Cyna AM, et al. Non-pharmacological interventions for assisting the induction of anaesthesia in children. Cochr Database Systemat Rev 2009;3:CD006447. [15] Patel A, Schieble T, Davidson M, et al. Distraction with a hand-held video game reduces pediatric preoperative anxiety. Paediatr Anaesth 2006;16:1019–27. [16] McQueen A, Cress C, Tothy A. Using a tablet computer during pediatric procedures a case series and review of the ‘‘apps’’. Pediatr Emerg Care 2012;28:712–4. [17] Griffiths MA, Kamat PP, McCracken CE, et al. Is procedural sedation with propofol acceptable for complex imaging? A comparison of short vs. prolonged sedations in children. Pediatr Radiol 2013. [18] Cravero JP, Beach ML, Blike GT, et al. The incidence and nature of adverse events during pediatric sedation/anesthesia with propofol for procedures outside the operating room: a report from the Pediatric Sedation Research Consortium. Anesth Analg 2009;108:795–804. [19] Stokes MA, Soriano SG, Tarbell NJ, et al. Anesthesia for stereotactic radiosurgery in children. J Neurosurg Anesthesiol 1995;7:100–8. [20] Buchsbaum JC, McMullen KP, Douglas JG, et al. Repetitive pediatric anesthesia in a non-hospital setting. Int J Radiat Oncol Biol Phys 2013;85:1296–300. [21] McFadyen JG, Pelly N, Orr RJ. Sedation and anesthesia for the pediatric patient undergoing radiation therapy. Curr Opin Anaesthesiol 2011;24:433–8. [22] Suneja G, Poorvu PD, Hill-Kayser C, et al. Acute toxicity of proton beam radiation for pediatric central nervous system malignancies. Pediatr Blood Cancer 2013.
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