The Risk of Kidney Injury in Patients With Sickle Cell Disease Treated With Ketorolac for Acute Pain.

Ketorolac, a nonsteroidal anti-inflammatory drug, is used in combination with opioids to manage vaso-occlusive episodes (VOEs). The relationship between ketorolac use and kidney injury in pediatric patients with sickle cell disease (SCD) remains incompletely understood. We hypothesize that ketorolac is associated with acute kidney injury (AKI) in patients with SCD presenting with pain. All nonsurgical hospitalizations for VOEs treated with ketorolac between January 2014 and December 2022 were included. We used optimal matching methodology to identify control admissions (2:1 ratio) and used nonparametric tests to compare ketorolac administration between cases and controls. A total of 1319 encounters/253 patients were included in this study. AKI was noted in 1.1% of encounters and 5.5% of patients. Cases had significantly higher initial BUN than controls (9.0 vs. 6.0 mg/dL, P=0.012). In cases versus controls, there was significantly lower serum sodium (136.0 vs. 138.0 mmol/L, P=0.021). There was no association between ketorolac dose and development of AKI among children with SCD. Higher BUN and lower sodium in cases suggest that patients with AKI were more volume depleted on admission than controls. This highlights the need for strict assessment of fluid status upon admission for VOE.

Cold Therapy for Pain Control in Pediatric Appendectomy Patients: A Randomized Controlled Trial.

PURPOSE: Topical ice has been shown to reduce pain scores and opioid use in adults with midline abdominal incisions. This study was designed to evaluate the efficacy of a cold therapy system in children following laparoscopic appendectomy. METHODS: Patients 7 years and older who underwent laparoscopic appendectomy at our institution from December 2021-September 2022 were eligible. Patients were randomized to standard pain therapy (control) or standard plus cold therapy (treatment) utilizing a modified ice machine system with cool abdominal pad postoperatively. Pain scores on the first 3 postoperative days (PODs), postoperative narcotic consumption, and patient satisfaction were analyzed. RESULTS: Fifty-eight patients were randomized, 29 to each group. Average survey response rate was 74% in control and 89% in treatment patients. There was no significant difference in median pain scores or narcotic use between groups. Cold therapy contributed to subjective pain improvement in 71%, 74%, and 50% of respondents on PODs 1, 2, and 3 respectively. CONCLUSION: A majority of patients reported cold therapy to be a helpful adjunct in pain control after appendectomy, though it did not reduce postoperative pain scores or narcotic use in our cohort - likely due to this population's naturally expedient recovery and low baseline narcotic requirement. TYPE OF STUDY: Randomized Controlled Trial. LEVEL OF EVIDENCE: Level I.

Ketamine use for management of vaso-occlusive pain in pediatric sickle cell disease.

BACKGROUND: Typical sickle cell disease (SCD) vaso-occlusive pain episode (VOE) management includes opioids, which are often inadequate and can be associated with significant side effects. Ketamine, a dissociative anesthetic, is a potentially effective adjunct to VOE management. OBJECTIVES: This study aimed to characterize ketamine use for VOE management in pediatric SCD. METHOD: This retrospective case series summarizes a single-center experience regarding the use of ketamine for inpatient management of pediatric VOE in 156 admissions from 2014 to 2020. RESULTS: Continuous low-dose ketamine infusion was most commonly prescribed to adolescents and young adults as an adjunct to opioids (median starting dose 2.0 µg/kg/min; median maximum dose 3.0 µg/kg/min). Ketamine was started a median of 13.7 hours after admission. Median ketamine infusion duration was 3 days. In most encounters, ketamine infusion was discontinued prior to opioid patient-controlled analgesia (PCA) discontinuation. The majority of encounters (79.3%) had a reduction in either PCA dose, continuous opioid infusion, or both while receiving ketamine. Low-dose ketamine infusion was associated with side effects noted in 21.8% (n = 34) of encounters. The most common side effects included dizziness (5.6%), hallucinations (5.1%), dissociation (2.6%), and sedation (1.9%). There were no reports of ketamine withdrawal. Most patients who received ketamine went on to receive it again during a subsequent admission. CONCLUSION: Further study is needed to determine the optimal timing of ketamine initiation and dosing. The variability of ketamine administration highlights the need for standardized protocols for ketamine use in VOE management.

Patient Controlled Analgesia for Vaso-Occlusive Episodes in Children: A Retrospective Study.

OBJECTIVE: To describe Patient-Controlled Analgesia (PCA) administration in pediatric patients admitted with sickle cell vaso-occlusive episode (VOE). METHODS: This single-center retrospective study included all inpatient hematology admissions for VOE between 2014 and 2020. PCA-ratio was calculated as the ratio of bolus over continuous IV opioids dose, and time to PCA adjustment as time between first PCA order and a subsequent order that increased dosing or changed opioid medication. RESULTS: A total of 866 encounters (172 unique patients) with PCA for VOE were included. The mean age was 15.4 years old (SD = 5.0). On average, after admission (hospital arrival), the first opioid dose was given at 1 hour, PCA started at 3.5 hours, and mean length of stay was 4.3 days (SD = 2.5). The mean initial PCA-ratio was 1.7 (SD = 0.6). There were no significant associations between age, gender, initial pain score, or admission hemoglobin and PCA-ratio (linear regression model P = 0.443). In 24.7% of encounters, the PCA was adjusted within 6 hours. After adjusting by age and gender, lower admission pain scores (OR = 1.15, P = 0.004), lower PCA-ratio (OR = 2.1, P = 0.003), longer time to PCA start (OR = 1.2, P = 0.001), and no adjuvant ketamine (OR = 2.4, P < 0.001) were associated with PCA unadjusted within 6 hours. CONCLUSION: At our institution, patients with VOE received opioids and PCA within the first hours of admission. PCAs were started at a ratio of 1.5-1.8, considered normal continuous. While no specific PCA-ratio was clearly superior for pain control, lower ratios (high continuous infusion) were associated with not requiring PCA adjustments at 6 hours. Prospective studies are needed.

Weaning Dexmedetomidine in Non-ICU Areas: An Implementation Effort.

OBJECTIVES: To develop and implement clinical practice guidelines for safely weaning dexmedetomidine infusions in non-ICU areas. DESIGN: Development, implementation, and analysis of effectiveness of clinical practice guidelines. SETTING: Quaternary care academic free-standing pediatric hospital. PATIENTS: Children, otherwise medically ready for transfer to non-ICU areas, who were undergoing a planned wean of a dexmedetomidine infusion. INTERVENTIONS: Subject matter experts developed evidence-based guidelines for weaning dexmedetomidine in patients whose critical phase of illness had resolved. MEASUREMENTS AND MAIN RESULTS: Searches identified no prospective studies of dexmedetomidine weaning. We identified two retrospective reviews of withdrawal symptoms and one on the use of clonidine. There were case studies on withdrawal symptoms. Guidelines were piloted on a cohort of 24 patients while in the ICU. The guidelines were then implemented in non-ICU areas for patients undergoing dexmedetomidine weaning after ICU transfer. Over a 2-year period (October 1, 2018, to September 30, 2020), 63 patients (1 mo to 18 yr old) successfully weaned dexmedetomidine in non-ICU areas. The median time to discontinuation of dexmedetomidine after transfer to non-ICU areas was 5.8 days (interquartile range, 4.75-15 d). Fifty-eight percent (n = 41) of all patients were considered high risk for dexmedetomidine withdrawal based on the dose, duration of exposure, and the risk of experiencing physiologic detriment with more than mild withdrawal. Twenty-nine patients (46%) exhibited no signs or symptoms of withdrawal while weaning per guidelines. For those with signs and symptoms of withdrawal, the most common were tachycardia (n = 26, 40%), agitation (n = 9, 14%), and hypertension (n = 9, 11%). CONCLUSIONS: Weaning dexmedetomidine in non-ICU areas is feasible and can be accomplished safely even among pediatric patients at high risk for withdrawal using standardized weaning guidelines. At our institution, implementation was associated with reduced ICU length of stay for patients recovering from critical illness.

Standardizing Opioid Prescribing in a Pediatric Hospital: A Quality Improvement Effort.

BACKGROUND: Opioids are indicated for moderate-to-severe pain caused by trauma, ischemia, surgery, cancer and sickle cell disease, and vaso-occlusive episodes (SCD-VOC). There is only limited evidence regarding the appropriate number of doses to prescribe for specific indications. Therefore, we developed and implemented an opioid prescribing algorithm with dosing guidelines for specific procedures and conditions. We aimed to reach and sustain 90% compliance within 1 year of implementation. METHODS: We conducted this quality improvement effort at a pediatric academic quaternary care institution. In 2018, a multidisciplinary team identified the need for a standard approach to opioid prescribing. The algorithm guides prescribers to evaluate the medical history, physical examination, red flags, pain type, and to initiate opioid-sparing interventions before prescribing opioids. Opioid prescriptions written between January 2015 and September 2020 were included. Examples from 2 hospital departments will be highlighted. Control charts for compliance with guidelines and variability in the doses prescribed are presented for selected procedures and conditions. RESULTS: Over 5 years, 83 037 opioid prescriptions in 53 804 unique patients were entered electronically. The encounters with ≥1 opioid prescription decreased from 48% to 25% between 2015 and 2019. Compliance with the specific guidelines increased to ∼85% for periacetabular osteotomies and SCD-VOC and close to 100% for anterior-cruciate ligament surgery. In all 3 procedures and conditions, variability in the number of doses prescribed decreased significantly. CONCLUSION: We developed an algorithm, guidelines, and a process for improvement. The number of opioid prescriptions and variability in opioid prescribing decreased. Future evaluation of specific initiatives within departments is needed.

Functional near-infrared spectroscopy to assess pain in neonatal circumcisions.

INTRODUCTION: Pain assessment is challenging in neonates. Behavioral and physiological pain scales do not assess neocortical nociception, essential to pain encoding and central pain pathway development. Functional near-infrared spectroscopy (fNIRS) can assess neocortical activation to noxious stimuli from changes in oxy-(HbO) and total-hemoglobin concentrations (HbT). This study aims to assess fNIRS nociceptive functional activation in the prefrontal cortex of neonates undergoing circumcision through changes in HbO and HbT, and the correlation between changes in fNIRS and Neonatal Infant Pain Scale (NIPS), a behavioral pain assessment scale. METHODS: In healthy term neonates, HbO, HbT, and NIPS were recorded during sequential circumcision events 1-Prep before local anesthetic injection; 2-Local anesthetic injection; 3-Prep before incision; 4-Oral sucrose; 5-Incision; 6-Gomco (hemostatic device) attached; 7-Gomco twisted on; and 8-Gomco removed. fNIRS and NIPS changes after each event were assessed with Wilcoxon signed-rank test and summarized as median and interquartile range (IQR). Changes in fNIRS vs. NIPS were correlated with Spearman coefficient. RESULTS: In 31 neonates fNIRS increased (median [IQR] µmol/L) with noxious events: Local injection (HbO: 1.1 [0.5, 3.1], p < .001; HbT: 2.3 [0.2, 7.6], p < .001), Gomco attached (HbO: 0.7 [0.1, 1.7], p = .002; HbT: 0.7 [-0.2, 2.9], p = .02), and Gomco twisted on (HbO: 0.5 [-0.2, 1.7], p = .03; HbT: 0.8 [-0.1, 3.3], p = .02). fNIRS decreased with non-noxious event: Prep before incision (HbO: -0.6 [-1.2, -0.2] p < .001; HbT: -1 [-1.8, -0.4], p < .001). Local anesthetic attenuated fNIRS increases to subsequent sharp stimuli. NIPS increased with subsequent sharp stimuli despite local anesthetic. Although fNIRS and NIPS changed in the same direction, there was not a strong correlation between them. CONCLUSIONS: During neonatal circumcision, changes in fNIRS differed between different types of painful stimuli, which was not the case for NIPS, suggesting that fNIRS may complement NIPS to assess the quality of pain.

A systematic review of ketamine for the management of vaso-occlusive pain in sickle cell disease.

Vaso-occlusive episodes (VOEs) are a common complication of sickle cell disease (SCD) and a significant cause of morbidity. Managing VOE pain can be difficult and complex. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been used to manage VOE pain. This systematic literature review synthesizes research published from 2010 to 2020 on the use of ketamine infusion to decrease VOE pain. The review demonstrates that ketamine, a safe and effective treatment for VOE pain, could be considered more widely. However, the significant variability among published clinical studies with regard to dosing, timing of initiation, duration of infusion, and timing of discontinuation highlights the need for standardized ketamine infusion protocols for the management of VOE pain. We conclude with a brief discussion of key components of a potential standardized protocol supported by the literature reviewed as well as areas for future investigation.

Initial Validation of GRASP: A Differential Diagnoses Algorithm for Children With Medical Complexity and an Unknown Source of Pain.

OBJECTIVES: Identifying the source of pain for children with medical complexity (MC) is challenging. The purpose of this study was the initial validation of a tool to guide the medical evaluation for identifying the source of pain in children with MC by using differential diagnoses. The tool is entitled Guidelines for Ruling Out and Assessing Source of Pain (GRASP). METHODS: A mixed-methods approach that included expert review, focus groups, Web-based surveys, and a trial of the GRASP was used to determine validity as well as perceived clinical utility. RESULTS: Focus groups were held with 26 inpatient and outpatient clinicians. Participants consistently responded in support of the GRASP. Participants advised several suggestions for tool organization such as designing the tool as a flow diagram. Seven clinicians participated in Web-based surveys and made specific suggestions for making the GRASP more comprehensive. Six participants trialed the GRASP for 14 children with MC and pain of unknown origin. Overall, participants found that the GRASP was a clinically effective tool for guiding medical evaluation. CONCLUSIONS: These results provide preliminary evidence that the GRASP has content and face validity in evaluating the source of pain in children with MC. This tool can be used to systematically guide clinicians through a balanced approach to evaluation with a goal of determining the pain source, preventing harm, and relieving suffering without unnecessary tests.

Effect of a Sedation Weaning Protocol on Safety and Medication Use among Hospitalized Children Post Critical Illness.

BACKGROUND: Best practice guidelines for the safe and compassionate care of critically ill children necessitates the use of sedation to ensure adequate ventilation, patient safety and comfort. Prolonged use of sedation can result in tolerance, physical dependence and iatrogenic withdrawal syndrome if medications are weaned too quickly. PROBLEM: In the context of medication errors related to parent administration of outpatient sedation weans, we set out to improve the safety of children weaning from sedatives. METHODS: A retrospective analysis was completed. Quality improvement was guided by using Plan-Do-Study-Act cycles. INTERVENTIONS: An evidence-based post PICU sedation weaning guideline was created and implemented over time with ongoing education, and review of progress with staff members with pre-post evaluation. RESULTS: Post intervention, there were significant differences in the numbers of patients discharged on home weaning from both opioids and benzodiazepines (11%, n = 24/219 pre; 3%, n = 7/233 post; p < 0.005). The number of patients discharged with a methadone wean decreased (7%, n = 16/219 pre; 0%, 0/233 post; p = 0.03). Despite these differences, there were no significant differences in the median hospital length of stay (42 pre; 39 post; p = 0.35). Post implementation more children had mild to moderate symptoms of withdrawal (11% pre; 21% post; p < 0.005) as compared to pre-implementation, however, the percentage of severe symptoms remained consistently low (0.6% pre; 1% post; p = 0.11). CONCLUSIONS: Implementation of an evidence-based post PICU weaning guideline significantly reduced the number of patients discharged on potentially dangerous medications with modest increases in mild-moderate symptoms of withdrawal and no significant change in length of stay or the incidence of severe symptoms of withdrawal.

An update on complex regional pain syndromes in children and adolescents.

PURPOSE OF REVIEW: Complex regional pain syndrome (CRPS) is a chronic pain condition typically involving a limb, which is characterized by neuropathic pain, sensory abnormalities and neurovascular findings. The exact cause of CRPS is unknown; however, proposed theories include alterations in the sympathetic and central nervous system (CNS), small fibre changes in the peripheral nervous system and psychological factors. Although this condition was previously considered rare among children and adolescents, it has been increasingly recognized in paediatric patients and can result in significant disability. RECENT FINDINGS: The diagnosis of paediatric CRPS is based upon clinical criteria obtained from a thorough history and physical examination. Other possible causes, such as orthopaedic, infectious, vascular and rheumatologic disorders, should be ruled out prior to making the diagnosis. Treatment focuses on a rehabilitative strategy consisting of physical therapy, occupational therapy and cognitive-behavioural therapy with an overall focus on return to functioning. SUMMARY: CRPS in children and adolescents is characterized by a painful, mottled appearing, swollen limb with allodynia and hyperalgesia. For most patients, pain is severe, resulting in significant functional disability. More recent evidence suggests that a rehabilitative programme results in improvement in both pain and functional measures.

Transdermal fentanyl in the management of children with chronic severe pain: results from an international study.

BACKGROUND: The current study was conducted to assess the safety and tolerability of a transdermal fentanyl delivery system for the relief of chronic pain in a pediatric population, and also to validate titration recommendations and conversion to transdermal fentanyl from oral opioid therapy. METHODS: This 15-day (with 3-month extension), single-arm, open-label trial was conducted at 66 sites in 10 countries. A total of 199 pediatric patients (ages 2-16 years) with both malignant and nonmalignant conditions who were receiving oral or parenteral opioids for moderate to severe chronic pain were enrolled. Transdermal fentanyl doses were titrated upward according to the rescue medication consumed during the previous application period. Degree of pain was assessed by patients and parents/guardians using visual and numeric scales. Level of play and quality of life were assessed using the Play Performance Scale (PPS) and the Child Health Questionnaire (CHQ). Adverse events were monitored on Days 1-15. Hypoventilation and sedation were monitored every 4 hours during the first 72 hours of the study. RESULTS: A total of 173 patients completed the primary treatment period and 130 entered the extension phase. The average daily pain intensity scores were reported to have decreased by Day 16 and improvements in the mean PPS scores were observed to the end of the extension period. The CHQ scores demonstrated improvements in 11 of 12 domains after Month 1 of the extension period. CONCLUSIONS: Transdermal fentanyl was found to be a safe and well tolerated alternative to oral opioid treatment for children ages 2-16 years who were previously exposed to opioid therapy.

Epidural abscess following epidural analgesia in pediatric patients.

Epidural abscess following epidural analgesia is an unusual event especially in pediatric patients. Two patients presented with fever and local signs of infection without neurological deficit on day 4 after the initiation of epidural analgesia. Neuro-imaging studies revealed epidural abscess. Both pediatric patients were treated successfully with intravenous antibiotics. One of the patients' initial MRI was normal. However, the symptoms persisted and a followed-up scan revealed epidural abscess. The other patient presented with worsening local indurations over the epidural insertion site and positive blood culture with Hemolytic streptococcus. Our experience suggests that neuro-imaging study should be strongly considered to evaluate pediatric patients with suspicion of epidural abscess.

Pain management for the hospitalized pediatric patient.

Pediatric hospitalists should make pain assessment and treatment a high priority and a central part of their daily practice. Efforts at improving pain treatment in pediatric hospitals should be multidisciplinary and should involve combined use of pharmacologic and nonpharmacologic approaches. Although available information can permit effective treatment of pain for most children in hospitals, there is a need for more research on pediatric analgesic pharmacology, various nonpharmacologic treatments, and different models of delivery of care.

Management of adolescent chronic pelvic pain from endometriosis: a pain center perspective.

OBJECTIVES: To review the options for the treatment of chronic pelvic pain in adolescents with endometriosis. METHODS: Review of publications and description of author's experience relating to adolescent endometriosis and pain treatment. RESULTS: Pain treatment services offer a multidisciplinary approach for the treatment of chronic pelvic pain consisting of analgesic trials, cognitive-behavioral therapy, physical therapy, and complementary and alternative therapies. Patients are also evaluated for other conditions that might contribute to their chronic pain. Medication trials of antidepressants, anticonvulsants, tramadol, and nonsteroidal anti-inflammatory drugs are frequently used; however, there are limited data on efficacy. Biobehavioral techniques such as relaxation and biofeedback can help patients modify their experience of pain. Cognitive behavioral therapy can improve coping skills and promote improved functioning, particularly in patients who are debilitated from chronic pain. Transcutaneous electrical stimulation (TENS) and physical therapy approaches may be helpful in patients with musculoskeletal conditions that contribute to their pelvic pain. Complementary and alternative therapies are frequently used in the treatment of chronic pain; controlled trials are needed to assess efficacy. CONCLUSIONS: An individualized, multidisciplinary approach may be effective in improving overall outcome in patients with chronic pelvic pain in reducing pain and normalizing function.