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In a single centre over two years, four children (7 to 10 years old) with upper limb osteosarcoma underwent chemotherapy followed by forequarter amputation. All patients had preoperative pain and were treated with gabapentin. Nerve sheath catheters were placed in the brachial plexus intraoperatively and left in situ for five to 14 days. After surgery, all patients received local anaesthetic infused via nerve sheath catheters as part of a multimodal analgesia technique. Three of the four patients were successfully treated as outpatients with the nerve sheath catheters in situ. All four children experienced phantom limb pain; however, it did not persist beyond four weeks in any patient. [ABSTRACT FROM AUTHOR]

We report three cases of children with osteosarcoma and pathologic fractures treated with long-term continuous nerve blocks for preoperative pain control. One patient with a left distal femoral diaphysis fracture had a femoral continuous nerve block catheter for 41 days without complications. Another with a fractured left proximal femoral shaft had three femoral continuous nerve block catheters for 33, 26 and 22 days respectively. The third patient, whose right proximal humerus was fractured, had a brachial plexus continuous nerve block catheter for 36 days without complication. In our experience, prolonged use of continuous nerve block is safe and effective in children with pathologic fractures for preoperative pain control. [ABSTRACT FROM AUTHOR]

Purpose: To determine the incidence of anesthesia-related complications in children undergoing radiotherapy and the associated risk factors.Methods and Materials: We retrospectively investigated the incidence and types of anesthesia-related complications and examined their association with age, weight, oncology diagnosis, type of anesthetic (propofol vs. propofol and adjuncts), total propofol dose, anesthetic duration, type of radiotherapy procedure (simulation vs. radiotherapy) and patient position (prone vs. supine).Results: Between July 2004 and June 2006, propofol was used in 3,833 procedures (3,611 radiotherapy sessions and 222 simulations) in 177 patients. Complications occurred during 49 anesthetic sessions (1.3%). On univariate analysis, four factors were significantly associated with the risk of complications: procedure duration (p <0.001), total propofol dose (p <0.001), use of adjunct agents (vs. propofol alone; p = 0.029), and simulation (vs. radiotherapy; p = 0.014). Patient position (prone vs. supine) was not significantly associated with the frequency of complications (odds ratio, 0.71; 95% confidence interval, 0.33-1.53; p = 0.38). On multivariate analysis, the procedure duration (p <0.0001) and total propofol dose (p < or =0.03) were the most significant risk factors after adjustment for age, weight, anesthetic type, and procedure type. We found no evidence of the development of tolerance to propofol.Conclusion: The rate of anesthesia-related complications was low (1.3%) in our study. The significant risk factors were procedure duration, total propofol dose, the use of adjunct agents with propofol, and simulation (vs. radiotherapy). [ABSTRACT FROM AUTHOR]

Background: Enhanced recovery after surgery (ERAS) protocols are multi-disciplinary approaches to standardize perioperative care. This is the first prospective, multi-institutional study to evaluate ERAS in pediatric patients undergoing abdominal tumor resections., Methods: All patients >1-month-old undergoing abdominal tumor resection at one of three children's hospitals between 2020 and 2022 were eligible. ERAS counseling was performed, and informed consent obtained. The ERAS protocol was standardized across institutions. We compared the prospective cohort to a propensity-matched historical cohort (2014-2020) from each institution utilizing 16 variables. Categorical variables were compared using McNemar's and/or Stuart-Maxwell testing. Continuous data was compared using logistic regression., Results: Ninety-five patients enrolled in the prospective cohort and were compared to 95 well-matched historic patients. Median LOS was 5.3 (4.1-7.2) days in the historic cohort, and 4.3 (3.3-6.2) days in the ERAS cohort (p = 0.053). Post-operative opioid consumption was lower in ERAS patients at 0.08 (0.03-0.16) MME mg/kg/day versus 0.23 (0.12-0.52) in historic patients (p = 0.013). ERAS patients received clear (POD#0, 0-0) and regular (POD#1, 1.0-1.0) diets two days sooner (both p < 0.001). ERAS patients ambulated two days sooner (1.0, 1.0-2.0 versus 3.0, 2.0-5.0). The number of patients who experienced any complication was significantly lower in the ERAS cohort (44, 44.2 %) compared to historic (82, 86.3 %, p < 0.001). This reduction was seen across each Clavien-Dindo grade 1-3 category (all p < 0.05)., Conclusion: ERAS protocols are feasible in pediatric patients undergoing abdominal tumor resections. Use of an ERAS protocol significantly reduced complications, opioid consumption, time to mobility, and time to diets., Level of Evidence: II., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This narrative review examines the evolving role of opioids in managing procedural and surgical pain in pediatric oncology patients. The review evaluates studies on opioid use across various oncological surgeries including thoracic, abdominal, orthopedic, and neurosurgical procedures, as well as for common painful procedures such as bone marrow aspirations and lumbar punctures. While opioids remain important for acute procedural and postoperative pain management in pediatric oncology patients, there is an increasing emphasis on multimodal, opioid-sparing approaches. The evidence presented within this review highlights the growing focus on judicious postoperative opioid prescribing to mitigate risks of adverse effects and persistent use or potential misuse. The review synthesizes findings from studies investigating various analgesic regimens, including the use of regional anesthesia techniques like epidural analgesia and peripheral nerve blocks, which have shown promise in reducing opioid requirements. For procedural pain, the review explores the efficacy of combining opioids with sedatives like midazolam or propofol, as well as the potential of ketamine as an opioid-sparing alternative. Key findings indicate that opioid-sparing techniques can effectively reduce overall opioid consumption without compromising pain control or patient satisfaction. Several studies demonstrated that regional anesthesia techniques and non-opioid adjuncts can significantly lower postoperative opioid requirements across various surgical procedures. For procedural pain, ketamine-based regimens often showed comparable or superior pain control to opioid-based approaches, with some studies reporting better patient satisfaction. This review also addresses the importance of tailored postoperative opioid prescribing, with some studies presenting algorithms to predict outpatient opioid needs more accurately. These approaches aim to ensure adequate pain control while minimizing excess opioid dispensing., Competing Interests: Declarations. Funding: No funding was received for the review or preparation of the manuscript. Conflict of Interest: All authors declare that they have no conflict of interest. Authors’ Contributions: Doralina L. Anghelescu and Elizabeth A. Hall led the article conception efforts. Hilary M. Jasmin performed the literature search. All authors contributed to the abstract screening, full-text review, and data extraction processes. All authors contributed to the preparation, review, and editing of the manuscript. All authors read and approved the final manuscript. Ethics Approval: Not applicable. Consent (Participation and Publication): Not applicable. Data Availability Statement: Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Code Availability: Not applicable., (© 2024. The Author(s).)

Opioid therapy is the mainstay for managing pain in pediatric oncology. This narrative review describes the current literature regarding opioids for pediatric cancer pain. The review explores the multifaceted landscape of opioid utilization in this population, including the role of opioids in certain clinical circumstances, modalities of opioid delivery, unique opioids, outpatient and at-home pain management strategies, and other key concepts such as breakthrough pain. This review highlights the importance of individualized dosing and multimodal approaches to enhance efficacy and minimize adverse effects. Drawing from a wide range of evidence, this review offers insights to optimize pediatric oncology pain management., (© 2024. The Author(s).)

Introduction: Enhanced recovery after surgery (ERAS) is an evidence-based, multi-modal approach to decrease surgical stress, expedite recovery, and improve postoperative outcomes. ERAS is increasingly being utilized in pediatric surgery. Its applicability to pediatric patients undergoing abdominal tumor resections remains unknown., Methods and Analysis: A group of key stakeholders adopted ERAS principles and developed a protocol suitable for the variable complexity of pediatric abdominal solid tumor resections. A multi-center, prospective, propensity-matched case control study was then developed to evaluate the feasibility of the protocol. A pilot-phase was utilized prior to enrollment of all patients older than one month of age undergoing any abdominal, retroperitoneal, or pelvic tumor resections. The primary outcome was 90-day complications per patient. Additional secondary outcomes included: ERAS protocol adherence, length of stay, time to administration of adjuvant chemotherapy, readmissions, reoperations, emergency room visits, pain scores, opioid usage, and differences in Quality of Recovery 9 scores., Ethics and Dissemination: Institutional review board approval was obtained at all participating centers. Informed consent was obtained from each participating patient. The results of this study will be presented at pertinent society meetings and published in peer-reviewed journals. We expect the results will inform peri-operative care for pediatric surgical oncology patients and provide guidance on initiation of ERAS programs. We anticipate this study will take four years to meet accrual targets and complete follow-up., Trial Registration Number: NCT04344899., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Mansfield, Kotagal, Hartman, Murphy, Davidoff, Anghelescu, Mecoli, Cost, Hogan and Rove.)

Pain is the hallmark symptom causing morbidity for people with sickle cell disease (SCD) and may present as nociceptive, neuropathic, or mixed type pain. Neuropathic pain (NP) is underrecognized and undertreated in patients with SCD and is associated with decreased patient-reported quality of life. Surveys were completed by clinicians caring for adolescents with SCD in the outpatient setting. SCD patients ages 1418 at increased risk of NP completed a patient-facing survey at a scheduled clinic visit. Ninety-four percent of responding clinicians agreed that NP significantly contributes to reported pain in SCD. Clinicians believed that NP medications are effective for reducing chronic pain (62%) and decreasing opioid utilization (44%). Clinician-identified barriers to prescribing NP medications included concerns about medication adherence (82%), lack of pediatric guidelines for NP medications (70%), and perceived patient concern about side effects (65%). More than 1/3 (35%) of clinicians reported that they were not comfortable managing NP medications. Clinician-identified barriers to referral to a pain management specialist included scheduling concerns (88%) and perceived patient/family lack of interest (77%). Most patients expressed willingness to take a medication for NP (78%), see a pain management specialist (84%), or learn more about nonpharmacologic interventions (72%), although most (51%) also reported some concerns about taking a medication for NP, citing insufficient knowledge (34%), and potential for side effects (32%). A minority of respondents (15%) worried about referral to a pain management specialist. Clinician and patient perspectives provide insights that may guide education efforts or other interventions to improve treatment of SCD-related NP., Competing Interests: Matthew Rees received support for travel and lodging expenses to attend an educational conference by Creative Educational Concepts. The conference was supported by a grant from Jazz Pharmaceuticals. No other authors declared any conflict of interest., (© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Context : Palliative sedation therapy (PST) can relieve suffering at end-of-life (EOL) in children with intolerable and refractory symptoms. However, updated and consistent guidance on PST practices are imperative. Objectives : We investigate current variations in clinical practice and PST implementation among pediatric palliative care (PPC) and pain management (PM) specialists. Methods : We distributed an IRB-exempt electronic anonymous survey via email through the Society of Pediatric Pain Medicine, and the American Academy of Hospice and Palliative Medicine. Survey responses were collated and descriptively reported. Results : Of 83 survey responses, the majority (75%) represented large academic children's hospitals. The distribution between PPC and pediatric pain management specialists' responses was 60% and 40%, respectively. Most respondents reported having designated pain management and/or palliative care teams (70% and 90%, respectively). Approximately half (48%) reported following an institutional PST protocol, most not requiring formal ethics consult (69%). Only 54% of respondents noted that the Do Not Resuscitate (DNR) order was required prior to PST initiation. PST was primarily utilized for children with oncologic diagnoses (76%). The primary and secondary medications of choice for PST implementation were reported to be opioids (39%) and benzodiazepines (36%) by pain management specialists, and benzodiazepines (52%) and barbiturates (28%) by palliative care specialists. Conclusions : Our study highlights the variability in the practice and implementation of PST. Further educational efforts are key for establishing PST practices and efficient protocol development.

Background: Patients undergoing limb amputation (LA) or limb-sparing (LS) for lower extremity oncologic diagnoses are at similar risk for chronic postsurgical pain of neuropathic nature (CPSP/NP). Regional anesthesia (RA) techniques are pre-emptive measures to prevent the occurrence of the CPS/NP. However, recommendations for epidural (EP) versus peripheral nerve blocks (PNBs) lack in pediatric literature., Aims: This study investigates the incidence and duration of CPSP/NP and describes NP-directed regimens., Methods and Results: Data on demographics, use of EP or PNB, duration of CPSP/NP, and NP-directed medication were retrospectively collected for LA and LS between 2009 and 2019. Mixed effects logistic regression was used to compare the odds of CPSP/NP between EP and PNB. Cox PH model with adjustment for clustering due to multiple surgeries on patients was used to quantify rate of pain relief between surgery groups (LA vs. LS) and RA groups (EP vs. PNB). The incidence of CPSP/NP was 36 (23.8%) after 165 surgeries (150 patients). The odds of CPSP/NP after PNB were 2.5 times those of CPSP/NP after EP (p = .11). The rate of pain relief at any instant after the EP was 1.2 times that after PNB (p = .3). The rate of pain relief for LS with EP was 1.9 times that of pain relief for LA with EP, a statistically significant difference (p = .03). Gabapentin was used (94.5%), with addition of amitriptyline (24.2%) and both amitriptyline and methadone (12.7%)., Conclusion: The LS with the EP group had a significantly higher rate of relief of CPSP/NP than LA with EP. Odds of CPSP/NP after PNB were 2.5 times those of CPSP after EP., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Objective: Recent increased awareness and research studies reflect possible associations between opioid exposure and cancer outcomes. Children with neuroblastoma (NB) often require opioid treatment for pain. However, associations between tumor response to chemotherapy and opioid exposure have not been investigated in clinical settings., Methods: This is a single-institution retrospective review of patients with NB treated between 2013 and 2016. We evaluated opioid consumption quantified in morphine equivalent doses (mg/kg) based on nurse- or patient-controlled analgesia during antibody infusions. We also analyzed their associations with change in primary tumor volume and total tumor burden., Results: Of 42 patients given opioids for pain related to anti-disialoganglioside monoclonal antibodies (anti-GD2 mAb), data completion was achieved for 36, and details of statistical analyses were entered. Median total weight-based morphine equivalent (over 8 days) was 4.71 mg/kg (interquartile range 3.49-7.96). We found a statistically insignificant weak negative relationship between total weight-based morphine equivalents and tumor volume ratio (correlation coefficient -.0103, p-value .9525) and a statistically insignificant weak positive relationship between total weight-based morphine equivalent and Curie score ratio (correlation coefficient .1096, p-value .5247)., Conclusion: Our study found no statistically significant correlation between opioid consumption and natural killer (NK) cell-mediated killing of NB cells as measured by effects on tumor volume/tumor load., (© 2022 Wiley Periodicals LLC.)

In recent years, there has been increased interest in using gabapentinoids (gabapentin and pregabalin) as part of multimodal medication plans or enhanced recovery after surgery protocols to mitigate several perioperative clinical challenges. Outcomes explored in the context of using gabapentinoids perioperatively in children are variable and include acute complications of pain, anxiety, nausea and vomiting, and emergence agitation, as well as the long-term postoperative outcome of chronic postsurgical pain. This narrative review describes the current literature regarding perioperative use of gabapentinoids in pediatric patients and aims to describe the role of gabapentinoids in the perioperative setting for each specific indication., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Context: Palliative sedation therapy (PST) can address suffering at the end of life (EOL) in children with cancer; yet, little is known about PST in this population. Objectives: We sought to describe the characteristics of pediatric oncology patients requiring PST at the EOL. Methods: A retrospective review was completed for pediatric oncology patients who required PST at a United States academic institution over 10 years, including demographics, disease characteristics, EOL characteristics, and medications for PST and symptom management. Results: PST was utilized in 3% of patients at the EOL. Of 24 study participants receiving PST, 83% ( n  = 20), 12.5% ( n  = 3), and 4.2% ( n  = 1) received dexmedetomidine, propofol, or both, respectively. The most frequent diagnosis for patients receiving PST was acute myelogenous leukemia (20.8%, n  = 5). All patients were followed up by the palliative care team, and two-thirds (66.6%, n  = 16) were also followed up by the pain management service; 79% ( n  = 19) were enrolled in hospice, and 98.5% ( n  = 23) had a Physician Orders for Scope of Treatment in place. Pain was the most common refractory symptom leading to PST initiation (33.3%, n  = 8), followed by neuroagitation and dyspnea. PST was initiated a median of 2.5 days before death. A third of deaths occurred in the intensive care unit (33.3%, n  = 8). Conclusions: PST was rare in this study; dexmedetomidine was used as first-line treatment for PST in patients at the EOL with refractory symptoms. Its place in PST protocols in pediatric oncology should be validated with prospective studies. Our study suggests the potential value of collaboration between palliative care and pain specialists in the context of PST.

Palliative sedation therapy (PST) is an important clinical intervention for pediatric patients with refractory symptoms and suffering during the end-of-life (EOL) period. Variations in PST implementation including medication selection, limited literature regarding feasibility in various clinical settings, particularly non-intensive care units, and lack of education on evolving definitions and ideal practices may all contribute to the current underutilization of this valuable resource. We therefore offer a clinical algorithm for identifying appropriate patients for PST, ensuring all other modalities for symptom management have been considered and/or optimized, and present a guideline for PST implementation that can be adapted and individualized based on institutional experience and resource availability. Furthermore, through case-based clinical scenarios, we demonstrate how to incorporate this algorithm into EOL practice.

Complex regional pain syndrome (CRPS) is a debilitating disorder that causes significant pain and can decrease the quality of life of affected individuals. This is the first report of CRPS in an adolescent oncology patient, whose symptoms successfully resolved with 3 weeks of intensive, multimodal, and multidisciplinary therapies. She experienced a complete return to pre-CRPS functional status within 10 weeks. The successful outcome of this case highlights the importance of early recognition of CRPS in the adolescent population and the need for a multimodal intensive treatment regimen to prevent the development of chronic pain and loss of limb function.

Context: Approximately 40%-60% of deaths in the pediatric intensive care unit (PICU) are in the context of de-escalation of life-sustaining treatments (LSTs), including compassionate extubation, withdrawal of vasopressors, or other LSTs. Suffering at the end of life (EOL) is often undertreated and underrecognized. Pain and poor quality of life are common concerns amongst parents and providers at a child's EOL. Integration of palliative care (PC) may decrease suffering and improve symptom management in many clinical situations; however, few studies have described medical management and symptom burden in children with cancer in the pediatric intensive care unit (PICU) undergoing de-escalation of LSTs., Methods: A retrospective chart review was completed for deceased pediatric oncology patients who experienced compassionate extubation and/or withdrawal of vasopressor support at EOL in the PICU. Demographics, EOL characteristics, and medication use for symptom management were abstracted. Descriptive analyses were applied., Results: Charts of 43 patients treated over a 10-year period were reviewed. Most patients (69.8%) were white males who had undergone hematopoietic stem cell transplantation and experienced compassionate extubation (67.4%) and/or withdrawal of vasopressor support (44.2%). The majority (88.3%) had a physician order for scope of treatment (POST - DNaR) in place an average of 13.9 days before death. PC was consulted for all but one patient; however, in 18.6% of cases, consultations occurred on the day of death. During EOL, many patients received medications to treat or prevent respiratory distress, pain, and agitation/anxiety. Sedative medications were utilized, specifically propofol (14%), dexmedetomidine (12%), or both (44%), often with opioids and benzodiazepines., Conclusions: Pediatric oncology patients undergoing de-escalation of LSTs experience symptoms of pain, anxiety, and respiratory distress during EOL. Dexmedetomidine and propofol may help prevent and/or relieve suffering during compassionate de-escalation of LSTs. Further efforts to optimize institutional policies, education, and collaborations between pediatric intensivists and PC teams are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cuviello, Pasli, Hurley, Bhatia, Anghelescu and Baker.)

Adolescents with sickle cell disease (SCD) have been shown to have pain-related sequelae following COVID-19 infection. In this case series, we discuss five adolescents with SCD and SARS-CoV-2 infection who subsequently developed complex pain circumstances manifested as: (1) increased frequency of acute care visits or admissions for pain; (2) new onset chronic pain; (3) new onset neuropathic pain; (4) escalation in the complexity of pharmacologic therapies; (5) increased use of nonpharmacologic interventions. While more research is needed to fully understand the implications of COVID-19 infection on pain in adolescents with SCD, these cases suggest the presence of a complex relationship., Competing Interests: The authors have no conflict of interest to report., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Ketamine is an NMDA-receptor antagonist with analgesic and opioid-sparing properties. Although well studied in adults, more robust evidence supporting ketamine's use for pediatric pain management is needed. This retrospective study evaluates ketamine's opioid-sparing effectiveness in pediatric and young adult oncology and hematology patients., Procedure: Continuous ketamine infusions administered for pain management between 2010-2020 were reviewed. Data including demographic characteristics, oncology/hematology and pain diagnoses, concurrent pain medications, and ketamine infusions' dose and duration were collected. Opioid consumption data based on delivery via patient-controlled analgesia were collected 1 day before (D1), all days during (cumulatively named D2), and 1 day after (D3) ketamine infusions and calculated as morphine-equivalent doses (mg/kg/day). Data were reported for the entire study group as well as for distinct oncology and end-of-life categories, and short-term acute pain circumstances which included vaso-occlusive crises in hematology patients. Side effects were reviewed., Results: Significantly lower daily opioid consumption was noted in the oncology group, while decreases were not significant in the end-of-life group and in the overall study population. The acute pain group did not show an opioid reduction associated with the ketamine infusions. A largely tolerable side-effect profile was observed, with no differences among each group's incidence., Conclusions: Ketamine infusions were associated with significantly reduced opioid consumption for oncology patients. The opioid-sparing effects of ketamine may vary according to clinical diagnoses and circumstances of use. Overall, low-dose ketamine infusions present an acceptable safety profile in pediatric and young adult patients; nevertheless, individual risks and benefits should be considered., (© 2022 Wiley Periodicals LLC.)

Background: Despite a more robust experience with lidocaine infusions for pain management in adults and general pediatric population, there is limited evidence of efficacy of lidocaine infusions for pain management in patients with pediatric hematology and oncology diagnoses., Methods: Data pertaining to continuous intravenous lidocaine infusions prescribed between January 2009 and June 2019 were reviewed, including patients' demographic characteristics, hematology/oncology and pain diagnoses, concurrent pain medications, and lidocaine infusion dose regimens and duration. Pain scores and opioid consumption calculations based on morphine equivalent doses (mg/kg/day) of patient-controlled analgesia were collected 1 day before infusion (D1), during infusion (D2), and 1 day after infusion (D3)., Results: The mean opioid consumption on D3 was significantly lower than that on D2 (p = .01). The pain scores on D3 were significantly lower than those on D1 when measured as average pain scores per 24 hours (p < .001) or as single pain scores immediately before and after infusions (p < .001). No significant associations were found between cumulative doses of lidocaine (loading dose plus total infusion dose) and either a decrease in the opioid consumption or a decrease in pain scores., Conclusions: In this retrospective series of pediatric hematology and oncology cases, we report positive outcomes in reducing opioid consumption and pain scores after lidocaine infusions. Prospective investigations designed in a collaborative, multi-institutional fashion, including a variety of pediatric populations are needed to further investigate the efficacy of lidocaine infusions., (© 2021 Wiley Periodicals LLC.)

This study retrospectively investigated psychological factors contributing to chronic post-surgical pain (CPSP) in pediatric patients after limb-sparing or amputation surgery for extremity osteosarcoma. Psychological factors were identified and analyzed by the Wilcoxon rank-sum and median two-sample tests. Univariate and multivariate Cox regressions were performed using gender, age, psychological factors, and psychological interventions related to CPSP duration as covariates. Duration of pain treatment was significantly longer in patients resistant to psychological interventions (p = 0.01) than those receptive to interventions. Shorter duration of pain treatment was associated with older age (p = 0.03) and receptiveness to psychological interventions (HR = 4.19, 95% CI [1.22, 14.35]). Older age and receptiveness to psychological interventions as part of pain management care are associated with needing a shorter duration of pain treatment. Our results highlight the importance of prospective investigations evaluating motivation to engage in psychotherapy and psychological interventions and identify risk factors for CPSP in pediatric oncology., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The goal of adequate pain control becomes increasingly salient for children with cancer and their families as the patients approach the end of life. Methadone is one option that is particularly desirable in end-of-life care given its long duration of action and NMDA antagonism that may help in controlling pain refractory to conventional opioids. The purpose of this study was to describe a single institution's experience with methadone for the treatment of cancer pain in pediatric end-of-life care., Methods: This retrospective, observational, single-center study included all patients during a 9-year period who died in the inpatient setting and were receiving methadone in their last 30 days of life., Results: Twenty patients were identified, 18 (90%) of whom received methadone for nociceptive pain. The median duration of methadone use was 32 days (range 2-323 days). Methadone doses ranged from 0.09 to 7.76 mg/kg per day. There were no instances of discontinuing methadone due to an increased QTc interval. No episodes of torsades de pointes were observed., Conclusion: In patients with pediatric cancer who are nearing the end of life, methadone is a valuable adjunctive therapy to treat nociceptive and neuropathic pain and to prevent opioid-induced hyperalgesia and opioid tolerance. An individualized approach to dosage and route should be considered based on specific clinical circumstances.

Lidocaine is an amino amide with a well-established role as a local anesthetic agent. Systemic intravenous administration expands its clinical use to include acute and chronic pain circumstances, such as postoperative pain, neuropathic pain, postherpetic neuralgia, hyperalgesia, visceral pain, and centrally mediated pain. For refractory pain that has not responded to conventional therapy or if further escalation of treatment is prevented by contraindications or side effects to standard therapies, a continuous infusion of lidocaine may be considered as a single intervention or as a sequence of infusions. Here, we review and evaluate published data reflecting the use of lidocaine continuous infusions for pain management in the pediatric population., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Although survivors of childhood cancer are at risk of chronic pain, the impact of pain on daily functioning is not well understood., Methods: A total of 2836 survivors (mean age, 32.2 years [SD, 8.5 years]; mean time since diagnosis, 23.7 years [SD, 8.2 years]) and 343 noncancer community controls (mean age, 35.5 years [SD, 10.2 years]) underwent comprehensive medical, neurocognitive, and physical performance assessments, and completed measures of pain, health-related quality of life (HRQOL), and social functioning. Multinomial logistic regression models, using odds ratios and 95% confidence intervals (95% CIs), examined associations between diagnosis, treatment exposures, chronic health conditions, and pain. Relative risks (RRs) between pain and neurocognition, physical performance, social functioning, and HRQOL were examined using modified Poisson regression., Results: Approximately 18% of survivors (95% CI, 16.1%-18.9%) versus 8% of controls (95% CI, 5.0%-10.9%) reported moderate to very severe pain with moderate to extreme daily interference (P < .001). Severe and life-threatening chronic health conditions were associated with an increased likelihood of pain with interference (odds ratio, 2.03; 95% CI, 1.62-2.54). Pain with daily interference was found to be associated with an increased risk of impaired neurocognition (attention: RR, 1.88 [95% CI, 1.46-2.41]; and memory: RR, 1.65 [95% CI, 1.25-2.17]), physical functioning (aerobic capacity: RR, 2.29 [95% CI, 1.84-2.84]; and mobility: RR, 1.71 [95% CI, 1.42-2.06]), social functioning (inability to hold a job and/or attend school: RR, 4.46 [95% CI, 3.45-5.76]; and assistance with routine and/or personal care needs: RR, 5.64 [95% CI, 3.92-8.10]), and HRQOL (physical: RR, 6.34 [95% CI, 5.04-7.98]; and emotional: RR, 2.83 [95% CI, 2.28-3.50])., Conclusions: Survivors of childhood cancer are at risk of pain and associated functional impairments. Survivors should be screened routinely for pain and interventions targeting pain interference are needed., (© 2020 American Cancer Society.)

Pain in sickle cell disease (SCD) can have a neuropathic component. This randomized phase II double-blinded placebo-controlled study evaluated the efficacy of gabapentin in reducing pain and opioid consumption (morphine-equivalent dose [MED]) during acute vaso-occlusive crisis (VOC). Of 90 patients aged 1-18 years with VOC pain, 45 were randomized to a single gabapentin dose (15 mg/kg) and 45 to placebo, in addition to standard treatment; 42 and 44 patients were evaluable in the gabapentin and placebo arms, respectively. A decrease in pain of ≥33% was reported in 68% of patients in the gabapentin arm and 60% of those in the placebo arm (one-sided p =  0.23). The median MED (mg/kg) in the gabapentin (0.12) and placebo arms (0.13) was similar ( p =  0.9). However, in the subset of patients with the HbSS genotype ( n  = 45), the mean (SD) absolute pain score decrease by the time of discharge was significantly greater in the gabapentin arm (5.9 [3.5]) than in the placebo arm (3.6 [3.3]) ( p =  0.032). Pain scores in the overall study population were not significantly reduced when gabapentin was added to standard treatment; however, gabapentin benefited individuals with the more severe genotype, HbSS, during acute VOC. Larger, prospective studies are needed to confirm these findings., Competing Interests: D.L.A., L.P., W.C.W., G.K., J.M.G., and O.M. have no conflict of interest. J.S.H. receives research support from Global Blood Therapeutics and consultant fees from Global Blood Therapeutics and MJ Lifesciences. K.N. is a Janssen R&D employee and a JNJ stockholder., (© 2021 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Aim: To examine whether anesthesia exposure is associated with neurocognitive decline in pediatric medulloblastoma., Methods: Patients were treated at St. Jude Children's Research Hospital and completed ≥2 protocol-directed neurocognitive assessments (n = 107) as part of a multisite clinical trial for pediatric medulloblastoma (NCT00085202). Patients received risk-adapted craniospinal photon irradiation, followed by four cycles of high-dose chemotherapy and stem cell rescue. Neurocognitive testing was completed at study baseline (after surgery and <2 weeks of starting radiation therapy) and annually for 5 years. Data on anesthesia exposure during treatment was abstracted from medical records., Results: Patients were 10.2 years at diagnosis on average (SD = 4.5; 37% female, 73% average-risk). Mean cumulative anesthesia duration was 20.4 h (SD = 15.2; range 0.7-55.6 h). In the overall group, longer anesthesia duration was associated with greater declines in IQ (Estimate = -0.08, P < 0.001), attention (Estimate = -0.10, P < .001) and processing speed (Estimate = -0.13, P < 0.001). Similar results were shown in subgroups of patients who were <7 years at diagnosis (IQ = -0.14, P = 0.027; Attention = -0.25: P = 0.011), ≥7 years at diagnosis (Attention = -0.07, P = 0.039; Processing Speed = -0.08, P = 0.022), treated for high-risk disease (IQ = -0.09, P = 0.024; Attention = -0.11, P = 0.034; Processing Speed = -0.13, P = 0.001), or treated for average-risk disease (IQ = -0.05, P = .022; Attention = -0.08, P = 0.011; Processing Speed = -0.10, P < 0.001)., Conclusion: Greater anesthesia exposure is a risk factor for clinically significant neurocognitive decline, in addition to factors of age at diagnosis and treatment risk arm. This result is notable as there are evidence-based strategies that can limit the need for anesthesia. Limiting anesthesia exposure, as feasible, may mitigate neurocognitive late effects, and thus, improve quality of life for survivors., Competing Interests: Conflict of interest statement Authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Children with acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits, and examining individual variability is essential to understand these risks. This study evaluated latent longitudinal trajectories and risk factors of neurocognitive outcomes in childhood ALL., Methods: There were 233 participants with ALL who were enrolled on a phase 3, risk-stratified chemotherapy-only clinical trial (NCT00137111) and who completed protocol-directed neurocognitive assessments [47.6% female, mean (SD) = 6.6 (3.7) years]. Measures of sustained attention, learning/memory, and parent ratings of attention were completed during and after treatment. Longitudinal latent class analyses were used to classify participants into distinct trajectories. Logistic regression was used to identify predictors of class membership., Results: Within the overall group, attention performance was below age expectations across time (Conners Continuous Performance Test detectability/variability, p < 0.01); memory performance and parent ratings were below expectations at later phases (California Verbal Learning Test learning slope, p < 0.05; Conners Parent Rating Scale, Revised attention/learning, p < 0.05). Most participants (80-89%) had stable neurocognitive profiles; smaller groups showed declining (3-6%) or improving (3-11%) trajectories. Older age (p = 0.020), female sex (p = 0.018), and experiencing sepsis (p = 0.047) were associated with greater attention problems over time. Lower baseline IQ was associated with improved memory (p = 0.035) and fewer ratings of attention problems (p = 0.013) over time., Conclusions: Most patients with ALL have stable neurocognitive profiles. Smaller groups have significant impairments shortly after diagnosis or have worsening performance over time. A tiered assessment approach, which includes consideration of individual and clinical risk factors, may be useful for monitoring neurocognitive functioning during treatment and survivorship., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: We developed an algorithm to decrease opioid prescriptions for pediatric oncology patients at discharge following surgery, based on a retrospective analysis to decrease variability and over-prescribing. The aim of this study was to prospectively test the algorithm., Methods: Opioid-naïve patients undergoing surgery for tumor resection at a single institution were included. A prescribing algorithm was developed based on surgical approach, day of discharge, and inpatient opioid use. Prospectively collected data included outpatient opioid consumption and patient/family satisfaction. Total home dose prescribed was equal to that used in the 8 or 24 h, depending on length of stay and operative approach, prior to discharge, divided into 0.15 mg/kg doses., Results: The algorithm was used in 121 patients and correctly predicted outpatient opioid requirements for 102 patients (84.3%). For 15 (12.4%) patients, the algorithm over-estimated opioid need by an average of 0.38 OME/kg. Four (3.3%) patients required additional opioids. Using this algorithm, we decreased overall opioid prescriptions from 6.17 to 0.21 OME/kg (p < 0.001), and all but one patient/family reported being satisfied with post-operative pain control., Conclusion: Using an algorithm based on inpatient opioid use, outpatient opioid needs can be accurately predicted, thereby reducing excess opioid prescriptions without detriment to patient satisfaction., Type of Study: Prospective Quality Initiative Study., Level of Evidence: Level III., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To evaluate the efficacy of gabapentin at 20 mg/kg per day in the treatment of vincristine-related neuropathic pain., Procedure: Children aged 1-18 years who developed vincristine-induced neuropathy on a St Jude frontline acute lymphoblastic leukemia trial were prospectively enrolled on a randomized, double-blind, placebo-controlled, phase II trial with two treatment arms: gabapentin plus opioid versus placebo plus opioid. Daily evaluations of morphine dose (mg/kg per day) and pain scores were conducted for up to 21 days; the values of the two arms were compared to assess analgesic efficacy., Results: Of 51 study participants, 49 were eligible for analyses. Twenty-five participants were treated with gabapentin, with a mean (SD) dose of 17.97 (2.76) mg/kg per day (median 18.26, range 6.82-21.37). The mean (SD) opioid doses taken, expressed as morphine equivalent daily (mg/kg per day), were 0.26 (0.43) in the gabapentin group (25 patients, 432 days) and 0.15 (0.22) in the placebo group (24 patients, 411 days; P = .15). Only the risk classification of acute lymphoblastic leukemia was significantly associated with the daily morphine dosage (P = .0178): patients in the lower risk arm received higher daily morphine dosages. Multivariate analyses revealed a significant difference between the groups' average daily scores for the previous 24 h and "right now.", Conclusion: In this population of children with vincristine-related neuropathic pain, opioid consumption and pain scores were higher in the gabapentin group than in the placebo group. Future randomized, double-blind, placebo-controlled studies should test gabapentin given longer or at a higher dose., (© 2020 Wiley Periodicals LLC.)

We evaluated pain status change and associations with subsequent opioid/marijuana use among 1208 adult survivors of childhood cancer. Pain status and opioid/marijuana were self-reported at baseline and follow-up evaluation (mean interval = 4.2 years). Over time, 18.7% of survivors endorsed persistent/increasing significant pain; 4.8% and 9.0% reported having used opioids and marijuana at follow-up. Persistent/increased (vs none/decreased) pain, persistent/increased (vs none/decreased) anxiety, and lack of health insurance increased odds of subsequent opioid use by 7.69-fold (95% confidence interval [CI] = 3.71 to 15.95), 2.55-fold (95% CI = 1.04 to 6.24), and 2.50-fold (95% CI = 1.07 to 5.82), respectively. Persistent/increased (vs none/decreased) depression increased odds of subsequent marijuana use by 2.64-fold (95% CI = 1.10 to 6.33)., (© The Author(s) 2020. Published by Oxford University Press.)

Objective: To evaluate the diagnostic yield of baseline chest radiographs (CXRs) of children with acute lymphoblastic leukemia (ALL)., Study Design: We reviewed the CXR findings at diagnosis for 990 patients aged 1-18 years with ALL treated during the Total XV and XVI studies at St. Jude Children's Research Hospital and evaluated the associations of these findings with clinical characteristics and initial management., Results: Common findings were peribronchial/perihilar thickening (n = 187 [19.0%]), pulmonary opacity/infiltrate (n = 159 [16.1%]), pleural effusion/thickening (n = 109 [11.1%]), mediastinal mass (n = 107 [10.9%]), and cardiomegaly (n = 68 [6.9%]). Portable CXRs provided results comparable with those obtained with 2-view films. Forty of 107 patients with a mediastinal mass (37.4%) had tracheal deviation/compression. Mediastinal mass, pleural effusion/thickening, and tracheal deviation/compression were more often associated with T-cell ALL than with B-cell ALL (P < .001 for all). Pulmonary opacity/infiltrate was associated with younger age (P = .003) and was more common in T-cell ALL than in B-cell ALL (P = .001). Peribronchial/perihilar thickening was associated with younger age (P < .001) and with positive central nervous system disease (P = .012). Patients with cardiomegaly were younger (P = .031), more often black than white (P = .007), and more often categorized as low risk than standard/high risk (P = .017). Patients with a mediastinal mass, pleural effusion/thickening, tracheal deviation/compression, or pulmonary opacity/infiltrate were more likely to receive less invasive sedation and more intensive care unit admissions and respiratory support (P ≤ .001 for all). Cardiomegaly was associated with intensive care unit admission (P = .008). No patients died of cardiorespiratory events during the initial 7 days of management., Conclusions: The CXR can detect various intrathoracic lesions and is helpful in planning initial management., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To examine the contribution of anesthesia exposure during treatment for childhood medulloblastoma to neurocognitive outcomes 3 years after tumor diagnosis., Study Design: In this retrospective study, anesthesia data were abstracted from medical records for 111 patients treated with risk-adapted protocol therapy at St Jude Children's Research Hospital. Neurocognitive testing data were obtained for 90.9% of patients., Results: For the 101 patients (62.4% male) who completed testing, mean age at diagnosis was 10.1 years, and 74.3% were staged to have average-risk disease. Anesthesia exposure during treatment ranged from 1 to 52 events (mean = 19.9); mean cumulative duration per patient was 21.1 hours (range 0.7-59.7). Compared with normative expectations (16%), the group had a significantly greater frequency of at-risk scores (<1 SD) on measures of intelligence (28.7%), attention (35.2%), working memory (26.6%), processing speed (46.7%), and reading (25.8%). Including anesthesia exposure duration to linear regression models accounting for age at diagnosis, treatment intensity, and baseline IQ significantly increased the predicted variance for intelligence (r 2  = 0.59), attention (r 2  = 0.29), working memory (r 2  = 0.31), processing speed (r 2  = 0.44), and reading (r 2  = 0.25; all P values <.001)., Conclusions: In survivors of childhood medulloblastoma, a neurodevelopmentally vulnerable population, greater exposure to anesthesia significantly and independently predicts deficits in neurocognitive and academic functioning. When feasible, anesthesia exposure during treatment should be reduced., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: This quality improvement initiative aimed to minimize opioid prescribing after oncologic pediatric surgery., Methods: Retrospective surgical data collected at a pediatric cancer hospital from July 2016 to June 2018 included hospitalization details, oral morphine equivalents prescribed, unplanned visits/calls because of pain, and parental/patient satisfaction with pain control. The quality improvement initiative promoted opioid prescription at discharge on the basis of prior inpatient requirements and education regarding nonopioid analgesia. Upon commencing this project in July 2018, we collected data prospectively., Results: The retrospective and the prospective cohorts included 271 and 99 patients, respectively. Mean (SD) oral morphine equivalents (mg/kg) prescribed upon discharge was significantly reduced in the prospective (0.75±1.34) versus retrospective cohorts (5.48±6.94, P<0.001). The unplanned visits/calls regarding pain were 23 (retrospective, 8.5%) and 2 (prospective, 2.0%). In total, 44 patients (44.4%) received an opioid prescription at discharge in the prospective cohort, significantly fewer than retrospective cohort (251, 92.6%, P<0.001), and used a mean of 34.3 of 159.8 (21.5%) doses dispensed. Length of stay was comparable (P=0.88) between cohorts. Prospective satisfaction rate was 96.2%, leaving 3 patients (3.8%) not satisfied with their pain control regimen., Conclusions: Dramatic reduction of opioid prescriptions after oncologic surgery can be achieved without detriment to patient satisfaction or readmissions., Level of Evidence: Level V.

Radiation-induced phantosmia has been reported both in children and adults. A fraction of these patients have nausea and vomiting triggered by phantosmia. Radiation-induced phantosmia, although transient, can be distressing enough to prevent a patient from staying still during radiation therapy. To date, specific interventions for radiation-induced phantosmia, including anesthesia, have not been reported. We report for the first time anesthesia as an intervention for transient severe radiation-induced phantosmia, in a 16-year-old girl with ependymoma undergoing proton therapy, and we discuss the pros and cons of techniques for anesthesia and airway management.

Background: Desmoplastic small round cell tumor (DSRCT) is a rare intra-abdominal soft tissue sarcoma affecting adolescents and young adults. Cytoreduction, hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), and adjuvant radiotherapy may improve local control. We review our experience with patients who undergo CRS/HIPEC and adjuvant radiotherapy for DSRCT., Methods: A retrospective review was performed for patients with DSRCT from 2013 to 2017 who underwent CRS/HIPEC. Clinicopathologic, operative, and outcome data were reviewed., Results: Ten CRS/HIPEC procedures were performed for nine patients (7 males, 6 Caucasian, median age 19 years (range 10-24)). Four patients presented with extra-abdominal disease; five had liver involvement. The median peritoneal cancer index was 16 (range 5-20). All received neoadjuvant chemotherapy. CCR 0/1 resection was possible in nine patients. Major complications occurred in four with no operative mortalities. All received adjuvant chemotherapy, seven received radiation therapy, and three received stem-cell transplant. All but one patient recurred after treatment. The median recurrence-free and overall survival (OS) were 12 and 45 months (95% confidence interval 35.1-54.9) respectively, with a 3-year OS of 55%. Long-term parenteral nutrition was required in eight for a median of 261 days (range 37-997). Clinically significant long-term complications requiring further surgery included gastroparesis (N = 1), small bowel obstruction (N = 3) and hemorrhagic cystitis (N = 2)., Conclusions: Multimodal therapy for DSRCT consisting of multiagent neoadjuvant chemotherapy, CRS/HIPEC, adjuvant chemotherapy, and radiation therapy is associated with potential cumulative toxicity. Recurrence after resection is common. Prolonged parenteral nutrition may be necessary, and late gastrointestinal and genitourinary complications may require additional treatment.

Purpose of Review: Recurrent exposure to opioids can lead to development of opioid tolerance and opioid-induced hyperalgesia through activation of N-methyl-D-aspartate receptors. N-methyl-D-aspartate receptor antagonists ketamine and lidocaine can modulate development of opioid tolerance and OIH. This study evaluated the utility of ketamine and/or lidocaine in decreasing opioid consumption during acute pain episodes in adolescents with sickle cell disease. There has been an increased effort to promote opioid-sparing pain relieving methods given the ongoing opioid epidemic., Recent Findings: There have been six studies published over the past decade that highlight the ability of ketamine to reduce opioid consumption in the management of sickle cell disease-related pain, primarily in adult patients. There has been one study (2015) that demonstrated a similar benefit with lidocaine, however this was also in adult patients., Summary: We retrospectively evaluated treatment with ketamine and/or lidocaine infusions in adolescents hospitalized for vaso-occlusive crisis (VOC). Patients served as self-controls using a comparison with a previous control admission for VOC. The use of ketamine and/or lidocaine as adjuncts to opioids resulted in lower daily opioid consumption in three of four patients. Our study suggests that ketamine and/or lidocaine infusions may be useful adjuncts in reducing opioid exposure during VOC pain.

Importance: Limited studies have reported associations between anesthesia and neurocognitive and neuroimaging outcomes, particularly in pediatric patients who undergo multiple exposures to anesthesia as part of chronic disease management., Objective: To investigate whether general anesthesia is associated with neurocognitive impairment and neuroimaging abnormalities in long-term survivors of childhood acute lymphoblastic leukemia., Design, Setting, and Participants: A cohort study of 212 survivors of childhood acute lymphoblastic leukemia who received treatment between July 7, 2000, and November 3, 2010, and follow-up at a mean (SD) of 7.7 (1.7) years post diagnosis, was conducted at an academic medical center. Of 301 survivors who were alive and eligible for participation, 217 individuals (72.1%) agreed to participate in long-term follow-up. Data analysis was performed from August 23, 2017, to May 3, 2018., Exposures: For 5699 anesthesia procedures, data on duration and cumulative doses of all anesthetics, sedatives, analgesics, anxiolytics, and neuromuscular blockers were abstracted, along with cumulative doses of high-dose intravenous methotrexate and number of triple intrathecal chemotherapy treatments., Main Outcomes and Measures: Neurocognitive measures of attention, processing speed, executive function, and intelligence were examined. Brain volumes, cortical thickness, and diffusion tensor imaging of the whole brain, corpus callosum, frontal lobes, and parietal lobes were evaluated., Results: Of the 217 study participants, 212 were included in both neurocognitive and brain imaging analysis. Of these, 105 were female (49.5%); mean (SD) age at diagnosis was 14.36 (4.79) years; time since diagnosis was 7.7 (1.7) years. Adjusting for chemotherapy doses and age at diagnosis, neurocognitive impairment was associated with higher propofol cumulative dose (relative risk [RR], 1.40 per 100 mg/kg; 95% CI, 1.11-1.75), flurane exposure (RR, 1.10 per exposure; 95% CI, 1.01-1.21), and longer anesthesia duration (RR, 1.03 per cumulative hour; 95% CI, 1.00-1.06). Slower processing speed was associated with higher propofol dose (estimate [est], -0.30; P = .04), greater number of exposures to fluranes (est, -0.14; P = .01), and longer anesthesia duration (est, -0.04; P = .003). Higher corpus callosum white matter diffusivity was associated with dose of propofol (est, 2.55; P = .01) and duration of anesthesia (est, 2.40; P = .02). Processing speed was significantly correlated with corpus callosum diffusivity (r = -0.26, P < .001)., Conclusions and Relevance: Higher cumulative anesthesia exposure and duration may be associated with neurocognitive impairment and neuroimaging abnormalities in long-term survivors of childhood acute lymphoblastic leukemia, beyond the known outcomes associated with neurotoxic chemotherapies. Anesthesia exposures should be limited in pediatric populations with chronic health conditions who undergo multiple medical procedures.

In recent years, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain have undergone substantial revisions focusing on the appropriate and safe prescription of opioid analgesics, optimization of nonopioid analgesics and adjuvant medications, and integration of nonpharmacologic methods of cancer pain management. This selection highlights some of these changes, covering topics on management of adult cancer pain including pharmacologic interventions, nonpharmacologic interventions, and treatment of specific cancer pain syndromes. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional aspects of this topic, including pathophysiologic classification of cancer pain syndromes, comprehensive pain assessment, management of pain crisis, ongoing care for cancer pain, pain in cancer survivors, and specialty consultations.

Pain and emotional distress are relevant risk factors as clinicians assess for aberrant opioid-associated behavior and provide adequate and responsible pain relief to patients who engage in behaviors that may be interpreted as drug seeking in nature. The present case illustrates how undertreated pain and treatment-related anxiety affected the opioid use of a young adult with cancer. Because these risk factors were identified during the initial consult, the treatment team was able to implement a multimodal and multidisciplinary treatment approach that provided the patient with better analgesia and coping skills for anxiety.

Neuropathic pain in pediatric oncology can be caused by distinct lesions or disease processes affecting the somatosensory system, including chemotherapy-related neuronal injury, solid tumor-related involvement of neural structures, post-surgical neuropathic pain-including phantom limb pain and pain after limb-sparing surgery-and the complex circumstances of neuropathic pain at the end of life. Treatment algorithms reflect the general treatment principles applied for adult neuropathic pain, but the dose regimens applied in children are modest and rarely escalated to the maximum doses to optimize analgesic efficacy. Pharmacological management of neuropathic pain should be based on a stepwise intervention strategy, as combinations of medications are the most effective approach. Gabapentinoids and tricyclic antidepressants are recommended as first-line therapy. Methadone, ketamine, and lidocaine may be useful adjuvants in selected patients. Prospective studies extended over a substantial length of time are recommended because of the nature of neuropathic pain as persistent, chronic pain and based on the need for sufficient time to escalate medication dose regimens to full analgesic efficacy.

The use of bisphosphonates for pain control in children with cancer is not extensively studied. We retrospectively evaluated 35 children with cancer treated with intravenous bisphosphonates for pain management at a single institution from 1998 through 2015. We analyzed pain scores and opioid and adjuvant medication consumption before bisphosphonate administration, daily for 2 weeks, and at 3 and 4 weeks after administration. We also determined the time interval between diagnosis and first administration of bisphosphonates and duration of life after bisphosphonate administration. Mean pain scores were 2.45 (±2.96) and 0.75 (±1.69) before and 14 days after bisphosphonate administration, respectively ( P = .25), and morphine equivalent doses of opioids were 5.52 (±13.35) and 5.27 (±9.77), respectively ( P = .07). Opioid consumption was significantly decreased at days 4 to 8, days 11 to 12, and week 3 after first bisphosphonate administration. The median duration of life after first bisphosphonate administration was 80 days, indicating its use late in the course of treatment. Bisphosphonates did not significantly improve pain outcomes at 2 weeks, but opioid consumption was reduced at several time points during the first 3 weeks. The use of bisphosphonates earlier in the course of pediatric oncological disease should be evaluated in prospective investigations.

Background:: Few studies have analyzed the benefit of limb amputations in children with metastatic osteosarcoma and limited life span., Objective:: We studied outcomes of limb amputations in children with metastatic osteosarcoma., Design:: We performed a retrospective review of patients who underwent limb amputations (January 1995-June 2015) and died within 1 year of surgery., Setting/participants:: We studied 12 patients with osteosarcoma at a single institution., Measurements:: Data on mobility, pain, and emotional and psychological well-being were retrieved from medical records from 1 month before surgery to 6 months after surgery., Results:: Of the 12 patients (7 females and 5 males; median age at surgery 13 years [range, 7-20 years]) meeting study criteria, 3 patients and 9 patients had primary osteosarcoma in upper and lower limbs, respectively. Mobility improved postamputation in 8 bedridden/wheelchair-bound patients. Postamputation, emotional, and psychological well-being improved for 9 patients, 3 patients had persistent psychological and/or emotional symptoms, and no patient experienced signs of regret. Daily mean pain scores were significantly lower at 1 week (median 3 [range, 0-6]; P = .03) and 3 months (median 0 [range, 0-8]; P = .02) postsurgery than at 1 week presurgery (median 5.5 [range, 0-10]). Morphine consumption (mg/kg/d) showed a trend toward higher values at 1 week (median 0.2 [range, 0-7.6]; P = .6) and 3 months (median 0.2 [range, 0-0.5]; P = .3) postsurgery than at 1 week presurgery (median 0.1 [range, 0-0.5])., Conclusions:: Patients undergoing limb amputations had reduced pain and improved mobility and emotional and psychological well-being. Amputations are likely to benefit children with limited life expectancy.

Background: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may improve survival., Methods: A retrospective review of anesthetic management and postoperative pain control strategies after CRS/HIPEC for DSRCT from 2013 to 2017 was performed., Results: The review analyzed 10 CRS/HIPEC procedures performed for nine DSRCT patients with a median age of 19 years (range 10-24 years). Six of these patients were Caucasian, and seven were men. The median operative duration was 551 min (range 510-725 min), and the median anesthesia duration was 621 min (range 480-820 min). Postoperative mechanical ventilation was necessary in 5 patients for a median duration of 1 day (range 0-2 days). The median intraoperative intravenous fluid administration was 13 ml/kg/h (range 6.3-24.4 ml/kg/h), and the colloid administration was 12 ml/kg (range 0.0-53.0 ml/kg). The median blood loss was 15 ml/kg (range 6.3-77.2 ml/kg). Nine patients received intraoperative transfusion with a median red blood cell transfusion volume of 14 ml/kg (range 10.1-58.5 ml/kg). The median intraoperative urine output was 2 ml/kg/h (range 0.09-8.40 ml/kg/h), and half of the patients received intraoperative diuretics. Cisplatin was used during HIPEC for eight surgeries. Acute kidney injury was observed in two patients, one of whom required short-term dialysis. Epidural infusions were used in eight cases for a median of 4 days (range 3-5 days). Postoperative intravenous opioid use (morphine equivalent) was 0.67 mg/kg/day (range 0.1-9.2 mg/kg/day) administered for a median of 11 days (range 2-35 days)., Conclusion: Cytoreduction and HIPEC for DSRCT are associated with significant perioperative fluid requirements and potentially challenging pain management. Renal protective strategies should be considered for reduction of cisplatin-associated nephrotoxicity. Further investigation for a more effective, less systemically toxic HIPEC agent is warranted.

Purpose: The use of celiac plexus block (CPB) for abdominal pain has been extensively reported in adults. However, pediatric literature is limited to three single case reports and a series of three cases. This study evaluated the effectiveness of CPB in children and young adults (aged 8-20 years) with abdominal malignancies. Methods: Pain outcomes after CPB were evaluated in four children and young adults with cancer. Mean daily pain score (PS, 0-10) and morphine consumption (intravenous morphine equivalent daily [MED], mg/kg/day) before and after CPB were used to assess effectiveness. Results: Mean daily PS reduced after CPB in all patients. In one patient, this reduction was sustained up to 6 months of follow-up, and analgesics were discontinued 1 week after CPB. The other three patients had limited survival (6, 16, and 37 days) after CPB. One patient had a PS of 0 over the last few days of life, but the MED was escalated from 0.74 before the block to 5.4 mg/kg/day at the end of life. In the other two patients, MED was lower during the first week after CPB than that before CPB (4.55 vs. 1.59 and 2.88 vs. 1.51 mg/kg/day, respectively). As these two patients had disease progression during their last days of life, the MED was increased to 4.75 and 263.9 mg/kg/day, respectively. Conclusions: Our results suggest that CPB may contribute to reducing PS and MED. We observed the use of CPB rather late in the disease trajectory.

Methadone is a synthetic opioid with unique pharmacodynamic and pharmacokinetic properties. It is effective in treating both nociceptive and neuropathic pain, which commonly co-exist in children with cancer. Upon reviewing the literature describing the use of methadone in pediatric oncology patients, publications are limited in number and low in quality of evidence; nevertheless, there is support for the safety and efficacy of methadone in treating pain in children with cancer, particularly when pain is refractory to conventional treatment. Although the risk of life-threatening arrhythmia is commonly cited as an argument against the use of methadone, our review of the literature did not support this finding in children. Further evaluation with prospective studies is warranted to develop evidence-based recommendations for the use of methadone in pediatric oncology.