Food allergy history and reaction to propofol administration in a large pediatric population.

BACKGROUND: Anaphylaxis to propofol is rare; however, providers face a clinical quandary as medication warnings still exist regarding propofol administration to egg-, soy-, and peanut-allergic patients. AIMS: The primary aim evaluated the rate of allergic reactions during propofol-containing anesthesia in patients listed allergic to egg, soy, or peanut compared with nonallergic patients who received propofol. The secondary aim evaluated the relationship between food allergy history and allergy testing data. METHODS: A retrospective chart review conducted between May 2012 and October 2018 identified pediatric patients listed allergic to egg, soy, and/or peanut, who received propofol. Allergy testing and results are presented. Evidence of allergic reaction to propofol during anesthesia was evaluated, and compared with a large nonallergic cohort who received propofol. RESULTS: Of the 232 392 anesthetics administered, 177 360 (76%) included propofol and 11308 (6%) involved a patient listed allergic to at least 1 index food. A large number of patients had no food allergy testing (n = 6153) or negative testing (n = 2198). Of the 3435 patients listed egg-allergic, 976 tested positive; 750 tested negative; and 1709 had no testing. Of the 2011 patients listed soy-allergic, 322 tested positive; 585 tested negative; and 1104 had no testing. Additionally, 5862 patients were listed peanut-allergic; 1659 tested positive; 863 tested negative and 3340 had no testing. One record of proven propofol anaphylaxis occurred; it was in a patient without a history of food allergies. There were 6 other cases of suspected allergy to propofol. One had a peanut and tree nut allergy and was lost to follow-up; one had no testing available, while 4 patients had positive propofol allergy testing and positive allergy tests to other medications. The rate of proven propofol anaphylaxis during anesthesia in the nonallergic cohort was 0.06/10 000, and the rate in egg- and soy-allergic patients was 0/5446. One patient with a listed peanut allergy had a possible reaction to propofol. CONCLUSIONS: In the listed food-allergic cohort, the majority had no allergy testing or negative testing. We found no evidence of a relationship between food allergy history and perioperative propofol reaction. We suggest multiply allergic and atopic patients may have a similar likelihood of propofol reaction as with other medications.

Electroencephalographic discontinuity during sevoflurane anesthesia in infants and children.

BACKGROUND: Deep anesthesia in adults may be associated with electroencephalographic (EEG) suppression and higher rates of postoperative complications. Little is known about the impact of anesthetic depth on short- or long-term outcomes in pediatrics. Brain activity monitoring may complement clinical signs of anesthetic depth. This prospective observational study aimed to assess the frequency and degree of profound EEG suppression using multichannel EEG in children during sevoflurane general anesthesia. METHODS: Children aged 0-40 months who required general anesthesia for elective surgery were included. Continuous EEG recordings were performed starting from when anesthesia began and until recovery. Discontinuity was defined as EEG amplitude <25 uV, lasting ≥2 s, and observed in all electrodes across the scalp. Frequency, duration, and inter-event interval of discontinuity events were measured. Relationships between discontinuity events and postnatal age, endtidal sevoflurane concentration (etSEVO), and multiple clinical parameters were analyzed. RESULTS: Discontinuity events were observed in 35/68 children, with a median duration of 10 s (95%CI: 8-12) and a median of 4 events per patient (95%CI: 2-7). Children who had discontinuity events were younger (5.5 months, 95%CI: 3.6-6.5) compared to children who did not have discontinuity events (10.2 months, 95%CI: 6.1-14); (difference between medians, 4.7 months, 95%CI: 2.3-8, P = 0.0002). Younger infants exhibited a higher number of discontinuity events, and the incidence decreased with postnatal age (r68 = -0.53, P < 0.0001). The majority of discontinuity events were observed during the first 30 min of anesthesia (66.4% total events), where etSEVO was >3%. Few discontinuity events were observed during maintenance and none during emergence. Blood pressure, heart rate, tissue oxygen saturation, and endtidal CO2 partial pressure did not change during these events. CONCLUSIONS: Electroencephalographic monitoring may complement clinical signs in providing information about brain homeostasis during general anesthesia. The impact of discontinuity events on immediate and long-term outcomes merits further study.

A Phase 1, Dose-escalation, Double-blind, Block-randomized, Controlled Trial of Safety and Efficacy of Neosaxitoxin Alone and in Combination with 0.2% Bupivacaine, with and without Epinephrine, for Cutaneous Anesthesia.

BACKGROUND: Neosaxitoxin (NeoSTX) is a site-1 sodium channel blocker that produces prolonged local anesthesia in animals and humans. Under a Food and Drug Administration-approved phase 1 Investigational New Drug trial, the authors evaluated safety and efficacy of NeoSTX alone and combined with 0.2% bupivacaine (Bup) with and without epinephrine. METHODS: The authors conducted a double-blind, randomized, controlled trial involving healthy male volunteers aged 18 to 35 yr receiving two 10-ml subcutaneous injections. Control sites received Bup. In part 1, active sites received (1) 5 to 40 µg NeoSTX+Saline (NeoSTX-Saline), (2) 5 to 40 µg NeoSTX+Bup (NeoSTX-Bup), or (3) placebo (Saline). In part 2, active sites received 10 or 30 µg NeoSTX+Bup+Epinephrine (NeoSTX-Bup-Epi) or placebo. Primary outcome measures were safety and adverse events associated with NeoSTX. Secondary outcomes included clinical biochemistry, NeoSTX pharmacokinetics, and cutaneous hypoesthesia. RESULTS: A total of 84 subjects were randomized and completed the two-part trial with no serious adverse events or clinically significant physiologic impairments. Perioral numbness and tingling increased with NeoSTX dose for NeoSTX-Saline and NeoSTX-Bup. All symptoms resolved without intervention. NeoSTX-Bup-Epi dramatically reduced symptoms compared with other NeoSTX combinations (tingling: 0 vs. 70%, P = 0.004; numbness: 0 vs. 60%, P = 0.013) at the same dose. Mean peak plasma NeoSTX concentration for NeoSTX-Bup-Epi was reduced at least two-fold compared with NeoSTX-Saline and NeoSTX-Bup (67 ± 14, 134 ± 63, and 164 ± 81 pg/ml, respectively; P = 0.016). NeoSTX-Bup showed prolonged cutaneous block duration compared with Bup, NeoSTX-Saline, or placebo, at all doses. Median time to near-complete recovery for 10 µg NeoSTX-Bup-Epi was almost five-fold longer compared with Bup (50 vs. 10 h, P = 0.007). CONCLUSION: NeoSTX combinations have a tolerable side effect profile and appear promising for prolonged local anesthesia.

Development and validation of a home quantitative sensory testing tool-kit to assess changes in sensory and pain processing: a study in healthy young adults.

ABSTRACT: Quantitative sensory testing (QST) is a set of methods for quantifying somatosensory functioning. Limitations of laboratory-based QST (LQST) include high cost, complexity in training, lack of portability, and time requirements for testing. Translating QST to a home setting could facilitate future research and clinical care. The objective of this study was to develop a home QST (HQST) tool-kit that is cost-effective, easy to use, and detects changes in sensory and pain processing. Thirty-two young healthy adults underwent sensory testing on their nondominant forearm using standard in-person LQST, followed by "simulated HQST" using video guidance in a separate room from the investigator before and after application of either a lidocaine or capsaicin cream. We observed good agreement between HQST and LQST scores, with significant correlations observed between the pinprick, pressure, cold and heat measures (|ρ| range = 0.36-0.54). The participants rated the HQST protocol as highly acceptable and safe but can be improved in future implementations. Home QST was able to detect hypoesthesia to vibration after lidocaine cream application (P = 0.024, d = 0.502) and could detect hypoalgesia and hyperalgesia to pressure and heat pain sensitivity tests after application of lidocaine and capsaicin creams, respectively (P-value range = <0.001-0.036, d-value range = 0.563-0.901). Despite limitations, HQST tool-kits may become a cost-effective, convenient, and scalable approach for improving sensory profiling in clinical care and clinical research.

Participatory research with an online drug forum: a survey of user characteristics, information sharing, and harm reduction views.

Visitors to a popular online drug forum completed an online survey between November 2011 and January 2012, which covered (1) demographic characteristics, (2) substance use (including nonmedical prescription opioid use), (3) forum activity, and (4) harm reduction beliefs. The study sample (N = 897) primarily included Caucasian males in their twenties from the United States, the United Kingdom, Australia, and Canada. The practice of harm reduction was overwhelmingly endorsed by participants. Current nonmedical prescription opioid users reported more activity in forums and past substance abuse treatment. The study's implications and limitations are noted and future research is suggested.

Clinical Characterization of Pediatric Erythromelalgia: A Single-Center Case Series.

Erythromelalgia is a descriptive term for severe burning pain and erythema in the distal extremities relieved by cold and exacerbated by heat. Pediatric case series to date are relatively small. We extracted and analyzed medical record data for 42 pediatric patients to describe clinical characteristics, associated conditions, and responses to treatments. Informed consent was obtained according to an IRB-approved protocol that included gene discovery. Three patients had confirmed Nav1.7 sodium channelopathies, with six additional patients under investigation with novel gene candidates. There was a female predominance (2.5:1), and the median onset age was 12 years (IQR = 3-14). Patients saw a median of three specialists (IQR = 2-3) for a diagnosis. The majority (90%) reported bilateral symptoms. Cooling methods usually provided partial relief, while heat and exercise exacerbated pain. No medication appeared to be consistently effective; commonly prescribed medications included sodium channel blockers (n = 37), topical analgesics (n = 26), gabapentin (n = 22), and aspirin (n = 15). Based on the currently published literature, we believe this cohort is the largest pediatric study of erythromelalgia to date. Many findings are consistent with those of previously published case series. Work is in progress to establish a prospective cohort and multi-center registry.

Tactile sensitivity and motor coordination in infancy: Effect of age, prior surgery, anaesthesia & critical illness.

BACKGROUND: Tactile sensitivity in the infant period is poorly characterized, particularly among children with prior surgery, anaesthesia or critical illness. The study aims were to investigate tactile sensitivity of the foot and the associated coordination of lower limb motor movement in typically developing infants with and without prior hospital experience, and to develop feasible bedside sensory testing protocols. MATERIALS AND METHODS: A prospective, longitudinal study in 69 infants at 2 and 4 months-old, with and without prior hospital admission. Mechanical stimuli were applied to the foot at graded innocuous and noxious intensities. Primary outcome measures were tactile and nociceptive threshold (lowest force required to evoke any leg movement, or brisk leg withdrawal, respectively), and specific motor flexion threshold (ankle-, knee-, hip-flexion). Secondary analysis investigated (i) single vs multiple trials reliability, and (ii) the effect of age and prior surgery, anaesthesia, or critical illness on mechanical threshold. RESULTS: Magnitude of evoked motor activity increased with stimulus intensity. Single trials had excellent reliability for knee and hip flexion at age 1-3m and 4-7m (ICC range: 0.8 to 0.98, p >0.05). Nociceptive threshold varied as a function of age. Tactile sensitivity was independent of age, number of surgeries, general anaesthesia and ICU stay. CONCLUSIONS: This brief sensory testing protocol may reliably measure tactile and nociceptive reactivity in human infants. Age predicts nociceptive threshold which likely reflects ongoing maturation of spinal and supraspinal circuits. Prior hospital experience has a negligible global effect on sensory processing demonstrating the resilience of the CNS in adverse environments.

Nusinersen for Patients With Spinal Muscular Atrophy: 1415 Doses via an Interdisciplinary Institutional Approach.

BACKGROUND: Spinal deformity and prior spinal fusion pose technical challenges to lumbar puncture (LP) for nusinersen administration for patients with spinal muscular atrophy (SMA). In this retrospective study over two study phases, we evaluated (1) factors associated with difficult LP or unscheduled requirement for image guidance and (2) effectiveness of a triage pathway for selective use of image guidance and nonstandard techniques, particularly for patients with spinal instrumentation/fusion to the sacrum. METHODS: With institutional review board approval, electronic health records, imaging, and administrative databases were analyzed for patients receiving nusinersen from January 2012 through September 2021. Descriptive statistics and univariate analyses were used. RESULTS: From January 2012 to March 2018 (phase 1), among 82 patients with SMA, 461 of 464 (99.4%) LP attempts were successful. Univariate analyses associated difficulty with prior spinal instrumentation, higher body mass index, and severity of the spinal deformity. Based on this experience, starting in April 2018 (phase 2), 125 patients were triaged selectively for ultrasound, fluoroscopy, or Dyna computed tomography. Patients with spinal instrumentation/fusion to the sacrum were treated primarily via intrathecal ports (137 doses) or transforaminal LP (55 doses). From April 2018 through September 2021, 704 of 709 (99.3%) LPs were successful. In total from January 2012 to September 2021, 1415 doses were administered. Over 50% of LPs were performed by neurology nurse practitioners without image guidance. Safety outcomes were excellent. CONCLUSIONS: A stratified approach resulted in successful intrathecal nusinersen delivery and efficient resource allocation for patients with SMA, with or without complex spinal anatomy.

The Effectiveness of Cancer Pain Management in a Tertiary Hospital Outpatient Pain Clinic in Thailand: A Prospective Observational Study.

Objectives: The objective was to examine the effectiveness of the updated approach. Methods: With IRB approval, outpatients with cancer were enrolled from January to December 2018. Assessments were recorded at baseline and three consecutive visits (BL, FU1, FU2, and FU3), including Numerical Rating Scale (NRS), the Brief Pain Inventory (BPI), the Edmonton Symptom Assessment System (ESAS), side effects, and analgesic use. The primary outcome was a favorable response, defined as an NRS decrease more than 30% or NRS <4. Secondary outcomes included trends over time in BPI, ESAS, side effects, and analgesic use. Pain response predictors at FU3 were analyzed using logistic regression. Results: Among 150 patients, 72 (48%) completed follow-ups. Of these, 61% achieved a favorable response at FU3. Pain interference diminished at all visits relative to baseline (p < 0.05). Median morphine equivalent daily dosage (MEDD) at BL was 20 mg/day, with a statistically significant, but clinically modest increase to 26.4 mg/day at FU3. Radiation therapy during pain care was a predictor of pain responders. Conclusion: The current Siriraj multidisciplinary approach provided effective relief of pain and stabilization of other cancer-related symptoms. Radiation therapy during pain care can be used to predict pain outcomes. Ongoing improvement domains were identified and considered in the context of cultural, economic, and geographic factors.

Developing a pediatric pain data repository.

The management of pediatric pain typically consists of individualized treatment plans and interventions that have not been systematically evaluated. There is an emerging need to create systems that can support the translation of clinical discoveries, facilitate the assessment of current interventions, and improve the collection of patient-centered data beyond routine clinical information. We present the development of the pediatric pain data repository, a custom-built system developed at Boston Children's Hospital by a multidisciplinary pain treatment service. The Repository employs a web platform to collect standardized patient-reported outcomes and integrates this with electronic medical record data. To date, we have collected information on 2577 patients and anticipate adding approximately 500 new patients per year. Major strengths of the Repository include collection of extensive longitudinal patient-reported outcomes, automated clinical data abstraction, and integration of the system into clinical workflows to support medical decision making.

Continuous Regional Anesthesia and Inpatient Rehabilitation for Pediatric Complex Regional Pain Syndrome.

BACKGROUND: Evidence supports treatment of pediatric complex regional pain syndromes (CRPS) with physical and occupational therapy and cognitive-behavioral therapy. Some patients have persistent pain and/or limb dysfunction despite these treatments. We performed a retrospective study of pediatric patients with CRPS treated by continuous epidural or peripheral perineural local anesthetic infusions along with inpatient rehabilitation at Boston Children's Hospital. METHODS: After approval from the institutional review board, electronic medical records were reviewed for patients treated between September 2003 and September 2014. Primary outcomes were pain and functional scores. Data were collected at the first encounter, at follow-up visits between 4 months before and after admission, and daily while inpatient. Changes over time were assessed using Wilcoxon tests with Dunn corrections. Clinical significance of benefit or harm was assessed by the method of Jacobson and Truax. Response predictors were analyzed using linear mixed models and exploratory logarithmic regression analyses. RESULTS: Pain, function, and disability scores improved during hospitalization and in follow-up over a 4-month period. Seventy percent of patients achieved clinically significant benefit (56% for pain reduction and 40% increased functionality, respectively). Univariate and adjusted predictors of favorable outcome included preadmission resting Numeric Pain Rating Scale score of less than 6 (odds ratio, 5.0; P = 0.0164 and subsequent attendance at the Pediatric Pain Rehabilitation Center at Boston Children's Hospital (odds ratio, 5.0; P = 0.0206). Mean pain scores greater than 3 during the regional anesthesia infusion predicted less favorable outcome. CONCLUSIONS: Continuous regional anesthesia may be an option to facilitate intensive rehabilitation for selected pediatric patients with CRPS. Further research should help clarify the role of regional anesthesia in a comprehensive management program.