Subanesthetic ketamine infusions for the treatment of children and adolescents with chronic pain: a longitudinal study

BACKGROUND: Chronic pain is common in children and adolescents and is often associated with severe functional disability and mood disorders. The pharmacological treatment of chronic pain in children and adolescents can be challenging, ineffective, and is mostly based on expert opinions and consensus. Ketamine, an N-methyl-D-aspartate receptor antagonist, has been used as an adjuvant for treatment of adult chronic pain and has been shown, in some instances, to improve pain and decrease opioid-requirement. We examined the effects of subanesthetic ketamine infusions on pain intensity and opioid use in children and adolescents with chronic pain syndromes treated in an outpatient setting. METHODS: Longitudinal cohort study of consecutive pediatric patients treated with subanesthetic ketamine infusions in a tertiary outpatient center. Outcome measurements included self-reported pain scores (numeric rating scale) and morphine-equivalent intake. RESULTS: Over a 15-month period, 63 children and adolescents (median age 15, interquartile range 12–17 years) with chronic pain received 277 ketamine infusions. Intravenous administration of subanesthetic doses of ketamine to children and adolescents on an outpatient basis was safe and not associated with psychotropic effects or hemodynamic perturbations. Overall, ketamine significantly reduced pain intensity (p <0.001) and yielded greater pain reduction in patients with complex regional pain syndrome (CRPS) than in patients with other chronic pain syndromes (p = 0.029). Ketamine-associated reductions in pain scores were the largest in postural orthostatic tachycardia syndrome (POTS) and trauma patients and the smallest in patients with chronic headache (p = 0.007). In 37 % of infusions, patients had a greater than 20 % reduction in pain score. Conversely, ketamine infusions did not change overall morphine-equivalent intake (p = 0.3). CONCLUSIONS: These data suggest that subanesthetic ketamine infusion is feasible in an outpatient setting and may benefit children and adolescents with chronic pain. Further, patients with CRPS, POTS, and a history of trauma-related chronic pain are more likely to benefit from this therapeutic modality

Analgesia and anesthesia for neonates:Study design and ethical issues

Objective: The purpose of this article is to summarize the clinical, methodologic, and ethical considerations for researchers interested in designing future trials in neonatal analgesia and anesthesia, hopefully stimulating additional research in this field. Methods: The MEDLINE, PubMed, EMBASE, and Cochrane register databases were searched using subject headings related to infant, newborn, neonate, analgesia, anesthesia, ethics, and study design. Cross-references and personal files were searched manually. Studies reporting original data or review articles related to these topics were assessed and critically evaluated by experts for each topical area. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were abstracted and synthesized in a systematic manner and refined by group members. Data synthesis and results were reviewed by a panel of independent experts and presented to a wider audience including clinicians, scientists, regulatory personnel, and industry representatives at the Newborn Drug Development Initiative workshop. Recommendations were revised after extensive discussions at the workshop and between committee members. Results: Designing clinical trials to investigate novel or currently available approaches for analgesia and anesthesia in neonates requires consideration of salient study designs and ethical issues. Conditions requiring treatment include pain/stress resulting from invasive procedures, surgical operations, inflammatory conditions, and routine neonatal intensive care. Study design considerations must define the inclusion and exclusion criteria, a rationale for stratification, the confounding effects of comorbid conditions, and other clinical factors. Significant ethical issues include the constraints of studying neonates, obtaining informed consent, making risk-benefit assessments, defining compensation or rewards for participation, safety considerations, the use of placebo controls, and the variability among institutional review boards in interpreting federal guidelines on human research. For optimal study design, investigators must formulate well-defined study questions, choose appropriate trial designs, estimate drug efficacy, calculate sample size, determine the duration of the studies, identify pharmacokinetic and pharmacodynamic parameters, and avoid drug-drug interactions. Specific outcome measures may include scoring on pain assessment scales, various biomarkers and their patterns of response, process outcomes (eg, length of stay, time to extubation), intermediate or long-term outcomes, and safety parameters. Conclusions: Much more research is needed in this field to formulate a scientifically sound, evidence-based, and clinically useful framework for management of anesthesia and analgesia in neonates. Newer study designs and additional ethical dilemmas may be defined with accumulating data in this field. Copyright (c) 2005 Excerpta Medica, Inc