Subanesthetic ketamine: the way forward for pain management in sickle cell disease patients?

INTRODUCTION: Patients with sickle cell disease (SCD) present recurrent episodes of acute pain, the hallmark of the disease, and some will also develop chronic pain. Currently, the treatment of SCD acute pain only targets its symptoms, rather than underlying mechanisms, and is directed by expert and consensus guidelines. AREAS COVERED: While opioids remain the mainstay of therapy for acute pain and are also used to treat SCD-related chronic pain, in some patients, opioids are ineffective or are associated with severe undesirable side effects. In those instances, clinicians caring for patients with SCD face an unmet need for effective non-opioid analgesics. Recently, the use of subanesthetic ketamine has been explored as a strategy to meet this need. While definitive evidence of its efficacy is lacking, some information exists suggesting that subanesthetic ketamine improves pain control and may have opioid-sparing effects in SCD-related acute pain. However, ketamine can also yield undesirable psychotomimetic and cardiovascular effects. EXPERT OPINION: After weighing potential risks and benefits, in the absence of better alternatives and in settings where it can be administered safely, ketamine may be a reasonable option for patients with SCD-related acute refractory pain.

Patient characteristics affect the response to ketamine and opioids during the treatment of vaso-occlusive episode-related pain in sickle cell disease.

BackgroundN-methyl-D-aspartate receptor activation has been implicated in the pathobiology of inflammatory, nociceptive and neuropathic pain, opioid tolerance, opioid-induced hyperalgesia, and central sensitization. Some of those mechanisms underlie sickle cell disease(SCD)-associated pain.MethodsWe conducted an exploratory cohort study of SCD patients who during vaso-occlusive episodes (VOEs) received subanesthetic doses of the N-methyl-D-aspartate receptor antagonist, ketamine, as an adjunct to opioids. We sought to identify predictors of changes in pain scores and of the percentage of ketamine infusions associated with meaningful changes (≥20% reduction) in pain and opioid consumption.ResultsEight-five patients received 181 ketamine infusions for VOE-associated pain. Combined with opioids, ketamine yielded significant decrease in pain scores and opioid consumption. Ketamine administered to males and to younger patients yielded greater pain score decrease compared with females (P=0.013) and older patients (P=0.018). Fifty-four percent of infusions yielded meaningful reductions in pain scores, and in multivariate analysis, sex, age group, pain location, and infusion duration independently predicted pain score changes.ConclusionThis study suggests that in SCD patients admitted with VOE-associated pain, ketamine has age- and sex-dependent effects. These data can inform sample and effect size calculations for controlled trials to determine which SCD patients would benefit most from ketamine.

Subanesthetic ketamine for pain management in hospitalized children, adolescents, and young adults: a single-center cohort study.

BACKGROUND: Subanesthetic doses of ketamine, an N-methyl-d-aspartate receptor antagonist used as an adjuvant to opioid for the treatment of pain in adults with acute and chronic pain, have been shown, in some instances, to improve pain intensity and to decrease opioid intake. However, less is known about the role of ketamine in pain management in children, adolescents, and young adults. PURPOSE: We examined the effects of subanesthetic ketamine on pain intensity and opioid intake in children, adolescents, and young adults with acute and chronic pain syndromes treated in an inpatient setting. METHODS: This is a longitudinal cohort study of patients treated with subanesthetic ketamine infusions in regular patient care units in a tertiary pediatric hospital. Primary outcomes included changes in pain scores and morphine-equivalent intake. RESULTS: The study cohort included 230 different patients who during 360 separate hospital admissions received subanesthetic ketamine infusions for pain management. Overall, ketamine infusions were associated with significant reductions in mean pain scores from baseline (mean pain scores 6.64 [95% CI: 6.38-6.90]) to those recorded on the day after discontinuation of ketamine (mean pain scores 4.38 [95% CI: 4.06-4.69]), p<0.001. Importantly, the effect of ketamine on pain scores varied according to clinical diagnosis (p=0.011), infusion duration (p=0.004), and pain location (p=0.004). Interestingly, greater reductions in pain scores were observed in patients with cancer pain and patients with pain associated with pancreatitis and Crohn's disease. There were no records of psychotomimetic side effects requiring therapy. CONCLUSION: These data suggest that administration of subanesthetic ketamine for pain management is feasible and safe in regular inpatient care units and may benefit children, adolescents, and young adults with acute and chronic pain. This study is informative and can be helpful in determining sample and effect sizes when planning clinical trials to determine the role of subanesthetic ketamine infusions for pain management in pediatric patients.

Melanocytic bronchopulmonary carcinoid tumor in a patient with multiple endocrine neoplasia syndrome type 1: a case report with emphasis on intraoperative cytological findings.

We present the cytological features along with histologic and imaging findings of a melanocytic bronchopulmonary carcinoid tumor in a patient with multiple endocrine neoplasia syndrome type 1 (MEN-1). Intraoperative touch preparations of the lung tumor showed single spindle cells and loosely cohesive aggregates of spindle cells with oval to elongated nuclei, "salt and pepper" chromatin pattern and inconspicuous nucleoli. The spindle cells occasionally contained cytoplasmic pigment, which revealed to be melanin by Fontana Masson stain on permanent processed material. Immunohistochemical stains for both synaptophysin and chromogranin were strongly positive in the spindle cells. The findings were consistent with melanocytic bronchopulmonary carcinoid tumor, which is relatively uncommon in MEN-1.