Brain Dynamics and Temporal Summation of Pain Predicts Neuropathic Pain Relief from Ketamine Infusion.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Ketamine is an N-methyl-D-aspartate receptor antagonist that reduces temporal summation of pain and modulates antinociception. Ketamine infusions can produce significant relief of neuropathic pain, but the treatment is resource intensive and can be associated with adverse effects. Thus, it is crucial to select patients who might benefit from this treatment. The authors tested the hypothesis that patients with enhanced temporal summation of pain and the capacity to modulate pain via the descending antinociceptive brain pathway are predisposed to obtain pain relief from ketamine. METHODS: Patients with refractory neuropathic pain (n = 30) and healthy controls underwent quantitative sensory testing and resting-state functional magnetic resonance imaging and then completed validated questionnaires. Patients then received outpatient intravenous ketamine (0.5 to 2 mg · kg · h; mean dose 1.1 mg · kg · h) for 6 h/day for 5 consecutive days. Pain was assessed 1 month later. Treatment response was defined as greater than or equal to 30% pain relief (i.e., reduction in pain scores). We determined the relationship between our primary outcome measure of pain relief with pretreatment temporal summation of pain and with brain imaging measures of dynamic functional connectivity between the default mode network and the descending antinociceptive brain pathway. RESULTS: Approximately 50% of patients achieved pain relief (mean ± SD; Responders, 61 ± 35%; Nonresponders, 7 ± 14%). Pretreatment temporal summation was associated with the effect of ketamine (ρ = -0.52, P = 0.003) and was significantly higher in Responders (median [25th, 75th] = 200 [100, 345]) compared with Nonresponders (44 [9, 92]; P = 0.001). Pretreatment dynamic connectivity was also associated with the clinical effect of ketamine (ρ = 0.51, P = 0.004) and was significantly higher in Responders (mean ± SD, 0.55 ± 0.05) compared with Nonresponders (0.51 ± 0.03; P = 0.006). Finally, the dynamic engagement of the descending antinociceptive system significantly mediated the relationship between pretreatment pain facilitation and pain relief (95% CI, 0.005 to 0.065). CONCLUSIONS: These findings suggest that brain and behavioral measures have the potential to prognosticate and develop ketamine-based personalized pain therapy.

Predictive Ability of Blood Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Gastrointestinal Stromal Tumors.

BACKGROUND: Recent findings have shown that the neutrophil-to-lymphocyte ratio (NLR) is prognostic for gastrointestinal stromal tumors (GIST). The platelet-to-lymphocyte ratio (PLR) can predict outcome for several other disease sites. This study evaluates the prognostic utility of NLR and PLR for patients with GIST. METHODS: All patients who had undergone surgical resection for primary, localized GIST from 2001 to 2011 were identified from a prospectively maintained database. Recurrence-free survival (RFS) was calculated by the Kaplan-Meier method and compared by the log-rank test. Univariate Cox proportional hazard regression models were used to identify associations with outcome variables. RESULTS: The study included 93 patients. High PLR [≥245; hazard ratio (HR) 3.690; 95 % confidence interval (CI) 1.066-12.821; p = 0.039], neutrophils (HR 1.224; 95 % CI 1.017-1.473; p = 0.033), and platelets (HR 1.005; 95 % CI 1.001-1.009; p = 0.013) were associated with worse RFS. Patients with high PLR had 2- and 5-year RFS of 57 and 57 %, compared with 94 and 84 % for those with low PLR. High NLR (≥2.04) was not associated with reduced RFS (p = 0.214). Whereas more patients in the high PLR group had large tumors (p = 0.047), more patients in the high NLR group had high mitotic rates (p = 0.016) than in the low-ratio cohorts. Adjuvant therapy was given to 41.2 % of the patients with high PLR (p = 0.022). The patients with high PLR/NLR had worse nomogram-predicted RFS than the patients with low PLR/NLR. CONCLUSIONS: High PLR was associated with reduced RFS. The prognostic ability of PLR to predict recurrence suggests that it may play a role in risk-stratification schemes used to determine which patients will benefit from adjuvant therapy.

International Multicenter Survey of Perioperative Management of External Ventricular Drains: Results of the EVD Aware Study.

INTRODUCTION: The perioperative management of patients with external ventricular drains (EVDs) is not well defined, and adherence to published management guidelines unknown. This study investigates practice, patterns, and variability in the perioperative management of patients with EVDs. METHODS: A 31-question survey was sent to 1830 anesthesiologists from 27 institutions in North America, Europe, and Asia. A perioperative EVD Guideline Adherence Score was calculated for the preoperative, transport and intraoperative periods. Differences in management practices between neuroanesthesiologists and non-neuroanesthesiologists, and factors affecting EVD guideline adherence, were examined using bivariate significance tests and linear regression. RESULTS: Among a sample of 599 anesthesiologists (survey response rate, 32.7%), compared with non-neuroanesthesiologists, neuroanesthesiologists were more likely to include baseline neurological examination (P=0.023), hourly cerebrospinal fluid output (P=0.006) and color (P<0.001), intracranial pressure trends (P<0.001), and EVD clamp trial (P<0.001) data in their routine preanesthetic assessment of patients with EVDs. There was a low prevalence of routine intracranial pressure monitoring during patient transport of patients with EVDs (14.4%). Overall, 25.9% of respondents were aware of EVD guidelines, and 21% reported receiving formal training in EVD management. The EVD Guideline Adherence Score was highest among anesthesiologists who reported being very comfortable in managing patients with EVDs compared with those who reported being uncomfortable (9.93 vs. 6.93, P<0.001). CONCLUSIONS: The EVD Aware study identifies opportunities for improvement in the perioperative management of patients with EVDS, including global awareness, formal EVD training, and dissemination of educational tools.

Perioperative Management of Adult Patients With External Ventricular and Lumbar Drains: Guidelines From the Society for Neuroscience in Anesthesiology and Critical Care.

External ventricular drains and lumbar drains are commonly used to divert cerebrospinal fluid and to measure cerebrospinal fluid pressure. Although commonly encountered in the perioperative setting and critical for the care of neurosurgical patients, there are no guidelines regarding their management in the perioperative period. To address this gap in the literature, The Society for Neuroscience in Anesthesiology & Critical Care tasked an expert group to generate evidence-based guidelines. The document generated targets clinicians involved in perioperative care of patients with indwelling external ventricular and lumbar drains.