A retrospective investigation of the relationship between neuroblastoma response to anti-GD2 monoclonal antibodies and exposure to opioids for pain management.

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.

Palliative Sedation Therapy in Pediatrics: An Algorithm and Clinical Practice Update.

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.

Low-dose ketamine infusions reduce opioid use in pediatric and young adult oncology patients.

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.

Liposomal Bupivacaine for Pediatric Celiac Plexus Block: A Case Report of Refractory Constipation Management.

Liposomal bupivacaine is a long-acting amide local anesthetic with a limited list of indications. At the time of publication, use is limited to field block and surgical wound infiltration and, more recently, interscalene nerve block. Although commonly used in adults, less is known about the safety and efficacy in pediatric patients. We present the use of liposomal bupivacaine for pediatric celiac plexus block in a 12-year-old boy suffering from gastrointestinal complications (eg, pain, constipation, and ileus) after bone marrow transplantation. Celiac plexus block utilizing liposomal bupivacaine was successfully used to palliate his pain and to normalize bowel function.

Lidocaine infusions and reduced opioid consumption-Retrospective experience in pediatric hematology and oncology patients with refractory pain.

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.

Retrospective analysis of predisposing factors for difficult lumbar punctures requiring image guidance in pediatric oncology patients.

Success rates of lumbar punctures (LPs) in children are reportedly as low as 50%. In addition to procedural complications and failure, difficult LPs are a risk factor for traumatic LPs (TLPs), which can potentially affect diagnostic utility and alter treatment plans for pediatric oncology patients. To identify the intrinsic factors associated with technically difficult LPs in the pediatric oncology population, we performed a retrospective review of patients who required diagnostic imaging modalities for LP procedures at a single pediatric oncology institution between September 2008 and November 2018. We evaluated data from 64 LPs performed in 33 patients who were referred for image-guided LPs after undergoing technically difficult LPs that were unsuccessful using anatomic landmarks. In these cases, 96.9% of patients had at least one of the following intrinsic factors: body mass index (BMI) ≥ 25, anatomic spinal abnormalities, history of ≥ 5 previous LPs, age < 12 months, and history of back surgery. Elevated BMI was the most common factor associated with difficult LP (81.8%), followed by spinal abnormalities (51.5%), and history of ≥ 5 previous LPs (33.3%). Age < 12 months and history of back surgery were also associated with difficult LPs, but at a lower frequency. On the basis of these findings, we propose clinical recommendations for preprocedural identification of patients at risk of difficult LPs to reduce complications, including TLP, failure, and exposure to general anesthesia.

Does epidural analgesia really enhance recovery in pediatric surgery patients?

PURPOSE: We sought to determine the benefits of epidural anesthesia (EA) in pediatric surgical patients. METHODS: This study is a single-institution retrospective review of EA for pediatric patients undergoing thoracotomy or laparotomy from 2015 to 2020. Patients with recent or chronic opioid use were excluded. Urgent or emergent cases, patients with hemodynamic instability, or those with surgical complications that significantly impacted their post-operative course were also excluded. The primary objectives were comparison of pain scores and systemic opioid use between those patients with EA and those without EA. RESULTS: Epidural anesthesia was used in 151 (81.6%) laparotomies and 58 (77.3%) thoracotomies. EA use was associated with lower mean systemic opioid administration during the early post-operative period for laparotomy (POD#0-0.33 ± 0.3 oral morphine equivalents per kilogram (OME/Kg) with EA vs 0.93 ± 1.53, p < 0.001, POD#1-1.34 ± 1.79 OME/Kg with EA vs 2.61 ± 2.60, p < 0.001) and thoracotomy (POD#0-0.40 ± 0.37 OME/Kg with EA vs 0.68 ± 0.41, p = 0.008, POD#1-0.89 ± 0.86 OME/Kg with EA vs 2.02 ± 1.92, p < 0.001). There were no differences seen by POD#2. Average pain scores were significantly lower in patients with EA following laparotomy (POD#0-1.22 ± 0.99 with EA vs 1.75 ± 1.33, p = 0.008) and thoracotomy (POD#0-1.71 ± 1.13 with EA vs 2.40 ± 1.52, p = 0.04). CONCLUSIONS: The use of EA in pediatric surgery patients was associated with lower pain scores despite lower systemic opioid requirements in the early post-operative period.

Epidural blood patch for post-dural puncture headaches in adult and paediatric patients with malignancies: a review.

Many anaesthetists are hesitant to perform epidural blood patch in patients with cancer because of the potential risk of seeding the CNS with malignant cells. Recent evidence suggests that anaesthetists may view malignancy as a relative contraindication to epidural blood patch rather than an absolute contraindication. This review article summarises the clinical dilemma, reviews the existing literature, and proposes a treatment algorithm that includes the utilisation of for the management of post-dural puncture headache in the oncology population.

Ketamine and lidocaine infusions decrease opioid consumption during vaso-occlusive crisis in adolescents with sickle cell disease.

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.

Pain Outcomes After Celiac Plexus Block in Children and Young Adults with Cancer.

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.

A Review of Adult and Pediatric Neuropathic Pain Assessment Tools.

OBJECTIVES: To identify and summarize the tools currently available for diagnosing and assessing neuropathic pain (NP) in adults and children and to identify areas where further research is required to address deficiencies in the existing tools. METHODS: A review of journal articles pertaining to the diagnosis and assessment of NP was conducted. RESULTS: We identified 11 tools for assessing NP in adults and 4 for assessing NP in pediatric patients. CONCLUSIONS: This article summarizes the various screening and assessment tools available to clinicians for evaluating NP. Despite the availability of the 15 tools discussed, a deficiency remains, particularly in the pediatric realm. To date, there is no well-validated NP assessment tool for children younger than 5 years, no pediatric NP screening tool that has been validated outside the domain of chemotherapy-induced peripheral neuropathy, and no consistent recommendation regarding the optimal tool to use with pediatric patients who have chronic pain. These areas, as well as others, would benefit from further research and development.