Richard Kline

The effect of intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery.

Background: Surgery induces a variety of metabolic, endocrine, and immune changes collectively known as the “stress response,” which may often lead to prolonged postoperative convalescence. Anesthetic management may modulate this physiological response, thus affecting the postoperative course. We hypothesized that the intraoperative administration of dexmedetomidine (DEX), a sympatholytic agent, would reduce the stress response and improve the quality of recovery in patients undergoing major surgery. Methods: We conducted a prospective randomized double-blinded study of 54 patients undergoing multilevel spinal fusion. Anesthesia was maintained using either propofol/fentanyl/dexmedetomidine (PFD) or propofol/fentanyl/placebo-saline (PFS). The quality of recovery (a primary endpoint) was assessed using a 40-item quality of recovery questionnaire and a 9-question Fatigue Severity Scores. The tests were carried out preoperatively on postoperative days (POD) 1, 2, 3, and 30. Blood samples were collected at baseline, in the postanesthesia care unit, and at POD 1 and were analyzed for levels of cortisol, C-reactive proteins (CRP), and cytokines interleukin (IL)-1&agr;, IL-1&bgr;, IL-1ra, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-&agr;. Data were analyzed using SPSS software (version 18) using a multivariate and mixed model approach to test for the effect of surgery and drug group. Pairwise comparisons were assessed by means of the t test or rank tests after correcting for multiple comparisons. Results: The global 40-item quality of recovery questionnaire scores showed a significant effect of time (F4,114=22.63, P<0.001) and drug (F1,51=4.368, P=0.042), with average scores decreasing to lower values on POD 1 (163.63±2.47) and POD 2 (170.94±2.38) compared with baseline (180.56±1.588, mean±SE, 2-tailed t tests, P<0.001). By POD 3, scores were significantly lower (−13.74 point difference, P=0.005) in the PFS group (169.3±3.87) than in the PFD group (183.04±2.76). All patients reported significantly higher levels of fatigue postoperatively, but intergroup difference in Fatigue Severity Scores was detected on POD 3 only, with scores in the PFS group higher than in the PFD group (50.0±4.0 vs. 36.3±4.9, P=0.035). In both groups, plasma cortisol levels were highest in the postanesthesia care unit, whereas CRP levels were elevated on POD 1. DEX significantly reduced the levels of cortisol, but not those of CRP. Levels of cytokines IL-6, IL-8, and IL-10 were significantly higher immediately after surgery and at POD 1. Plasma levels of other cytokines were not affected by surgery. DEX delayed postoperative rise in IL-10 but not in IL-6 or IL-8. Conclusions: DEX infusion during multilevel spinal fusions moderately improved the quality of recovery and possibly reduced fatigue in the early postoperative period. Moreover, it reduced plasma levels of cortisol and IL-10 in comparison with the control group. Our sample size was not sufficient to detect differences either in the incidence of complications or in clinically relevant outcomes.

Surgery and Brain Atrophy In Cognitively Normal Elderly Subjects and Subjects Diagnosed with Mild Cognitive Impairment

Background: Structural magnetic resonance imaging is used to longitudinally monitor the progression of Alzheimer disease from its presymptomatic to symptomatic phases. Using magnetic resonance imaging data from the Alzheimers Disease Neuroimaging Initiative, we tested the hypothesis that surgery would impact brain parameters associated with progression of dementia. Methods: Brain images from the neuroimaging initiative database were used to study normal volunteer subjects and patients with mild cognitive impairment for the age group 55 to 90 inclusive. We compared changes in regional brain anatomy for three visits that defined two intervisit intervals for a surgical cohort (n = 41) and a propensity matched nonsurgical control cohort (n = 123). The first interval for the surgical cohort contained the surgical date. Regional brain volumes were determined with Freesurfer and quantitatively described with J-image software (University of California at San Francisco, San Francisco, California). Statistical analysis used Repeated Measures ANCOVA (SPSS, v.18.0; Chicago, IL). Results: We found that surgical patients, during the first follow-up interval (5–9 months), but not subsequently, had increased rates of atrophy for cortical gray matter and hippocampus, and lateral ventricle enlargement, as compared with nonsurgical controls. A composite score of five cognitive tests during this interval showed reduced performance for surgical patients with mild cognitive impairment. Conclusions: Elderly subjects after surgery experienced an increased rate of brain atrophy during the initial evaluation interval, a time associated with enhanced risk for postoperative cognitive dysfunction. Although there was no difference in atrophy rate by diagnosis, subjects with mild cognitive impairment suffered greater subsequent cognitive effects.

Meloxicam improves object recognition memory and modulates glial activation after splenectomy in mice.

Context Surgery-induced neuroinflammation has been implicated in the development of postoperative cognitive dysfunction (POCD). Objective To test the hypothesis that meloxicam, a selective cyclooxygenase (COX)-2 inhibitor, preserves postoperative cognitive function and inhibits surgery-induced neuroinflammation in a mouse model. Design A mouse model of splenectomy-induced inflammation. Methods Sixty Swiss Webster male mice (6–8 week old) were randomised into six groups that underwent splenectomy. Animals in groups 1–4 were tested once on day 1, 5, 9 or 14 to determine the time course of delayed transient cognitive dysfunction associated with splenectomy. Animals in groups 5 and 6 were tested once on day 5 or 9 to determine the ability of the NSAID meloxicam to attenuate cognitive dysfunction. Intervention Animals in groups 1–4 received one dose 500 &mgr;l intraperitoneal physiological saline 24 h after splenectomy. Animals in groups 5 and 6 received one dose of intraperitoneal meloxicam (60 mg kg in 500 &mgr;l saline) 24 h after splenectomy. Main outcome measures Short-term working memory as determined by Object Recognition Test (ORT) index on days 1, 5, 9 and 14 was the first main outcome. Tomato lectin staining histochemistry of glial cells was assessed on days 1, 5, 9 and 14 as a second main outcome. Results Compared with day 1 (group 1), the mean ORT indices at day 5 (group 2) and day 9 (group 3) were decreased by 27.5% [95% confidence interval (CI): 0.9 to 54.1%, P = 0.04] and 23.8% (95% CI, 4.3 to 51.9%, P = 0.09), respectively. At day 5 (group 5) and day 9 (group 6), the ORT indices in the meloxicam groups were reduced by 6.6% (95% CI: −11.4 to 24.5%) and 4.3% (95% CI: −25.3 to 34.0). Thus, the administration of meloxicam attenuated the decrease in ORT indices (P = 0.031). Histochemical staining with tomato lectin showed features of microglia activation at day 5 and 9, which was reduced by the administration of meloxicam. Conclusion These findings suggest that COX-2-dependent mechanisms may play a role in the development of POCD. This effect may be dependent on the modulation of glial cell activation.

Efficacy of Clevidipine in Controlling Perioperative Hypertension in Neurosurgical Patients: Initial Single-center Experience

Background Acute blood pressure (BP) elevations in neurosurgical patients are associated with serious neurologic, cardiovascular, or surgical site complications. Clevidipine, an ultra-short-acting dihydropyridine calcium antagonist, has been shown to be efficacious and safe for acute hypertension in cardiac surgery. This study assessed the efficacy and safety of clevidipine in controlling perioperative hypertension in the neurosurgical setting. Methods Patients scheduled for intracranial surgery were prospectively enrolled after giving consent. Clevidipine (0.5 mg/mL in 20% lipid solution, which was to be initiated at 10 mg/h and titrated to effect) was administered as the primary antihypertensive agent for perioperative hypertension, with target BPs of less than 130 mm Hg. Other vasoactive drugs were administered as needed for treating systolic BP (SBP) less than 90 mm Hg or greater than 130 mm Hg. The primary study endpoint was the proportion of patients not requiring rescue antihypertensives to maintain target SBP (<130 mm Hg). Results Twenty-two patients were enrolled. One patient did not require antihypertensive therapy. Seventeen patients (17 of 21, 81%) were treated with clevidipine alone; one received clevidipine in the postanesthesia care unit only. Twenty-eight hypertensive episodes (defined as any new acute BP elevation requiring clevidipine initiation) were documented. SBP was reduced to target level within 15 minutes in 22 of 28 episodes (78.6%). Two mild hypotensive episodes occurred after the initiation of clevidipine infusion; these transient decreases in BP were treated with vasoactive drugs and resolved within 5 minutes. Conclusions Clevidipine is effective and safe for perioperative hypertension in patients undergoing intracranial procedures. Rapid control of BP is possible with higher starting doses. Drug effects resolved rapidly after drug discontinuation.

Despite differences in cytosolic calcium regulation, lidocaine toxicity is similar in adult and neonatal rat dorsal root ganglia in vitro.

Background:Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action of local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, the authors examined whether there were any differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons. Methods:DRG neurons were cultured from postnatal day 7 (P7) and adult rats. Lidocaine-induced changes in cytosolic calcium were examined with the calcium indicator Fluo-4. Cells were incubated with varying concentrations of lidocaine and examined for viability using calcein AM and ethidium homodimer-1 staining. Live imaging of caspase-3/7 activation was performed after incubation with lidocaine. Results:The mean KCl-induced calcium transient was greater in P7 neurons (P < 0.05), and lidocaine significantly inhibited KCl-induced calcium responses in both ages (P < 0.05). Frequency distribution histograms of KCl-evoked calcium increases were more heterogeneous in P7 than in adult neurons. With lidocaine, KCl-induced calcium transients in both ages became more homogeneous but remained different between the groups. Interestingly, cell viability was decreased by lidocaine in a dose-dependent manner similarly in both ages. Lidocaine treatment also activated caspase-3/7 in a dose- and time-dependent manner similarly in both ages. Conclusions:Despite physiological differences in P7 and adult DRG neurons, lidocaine cytotoxicity is similar in P7 and adult DRG neurons in vitro. Differences in lidocaine- and KCl-evoked calcium responses suggest the similarity in lidocaine cytotoxicity involves other actions in addition to lidocaine-evoked effects on cytosolic calcium responses.

Both lavender fleur oil and unscented oil aromatherapy reduce preoperative anxiety in breast surgery patients: a randomized trial.

STUDY OBJECTIVE The objective of this study was to determine whether lavender fleur oil (LFO) aromatherapy would reduce anxiety when administered to women before undergoing breast surgery. DESIGN This was a single-site, randomized study comparing the effect of LFO to unscented oil (UO). SETTING The study was conducted in the preoperative holding area of the ambulatory surgery department of NYU Langone Medical Center. PATIENTS Ninety three women, 18 years and older, scheduled for breast surgery. Women meeting inclusion/exclusion criteria were randomized to either LFO or UO aromatherapy and were blind to their assigned treatment. OUTCOME MEASURES Subjects completed a Speilberger State Anxiety Inventory for Adults (STAI) before and after aromatherapy. Vital signs were recorded before and after aromatherapy. RESULTS STAI-State questions were divided into positive and negative emotions for analysis. Before aromatherapy, there was no significant difference between groups by individual questions or overall average answer of either positive or negative questions. The use of both LFO and UO increased the positive STAI score totals, with the LFO group having a slightly, but statistically significant, greater increase. Both resulted in a statistically significant decrease in the negative score totals after treatment. There were no differences in vital signs between groups for either treatment. Following the conclusion of the trial LFO was analyzed and found to contain a very low content of the 2 major Lavandula angustifolia constituents. CONCLUSIONS Both LFO and UO aromatherapy treatments lowered anxiety before surgery despite no significant changes in vital signs. LFO treatment generated a slight but statistically significant increase in positive feelings compared with UO treatment. It is probable that the beneficial effect observed was due to both aromatherapy with LFO and a placebo effect related to the added attention given to the patients.

Impact of analgesics on executive function and memory in the Alzheimer's Disease Neuroimaging Initiative Database

Abstract Background and aims Pain is common in older adults but may be undertreated in part due to concerns about medication toxicity. Analgesics may affect cognition. In this retrospective cohort study, we used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to examine the interaction of cognitive status and medications, especially non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesized NSAID use would be associated with cognition and that this could be mediated through changes in brain structure. Methods In this post hoc analysis of the ADNI database, subjects were selected by searching the “concurrent medications log” for analgesic medications. Subjects were included if the analgesic was listed on the medication log prior to enrollment in ADNI and throughout the study. Subjects taking analgesics, particularly NSAIDs, at each study visit were compared to control subjects taking no analgesics. Using descriptive statistics as well as univariate, multivariate and repeated measure ANOVA, we explored the relationship between NSAID use and scores for executive function and memory related cognitive activities. We further took advantage of the extensive magnetic resonance imaging (MRI) data available in ADNI to test whether cognitive change was associated with brain structure. The multitude of imaging variables was compressed into a small number of features (five eigenvectors (EV)) using principal component analysis. Results There were 87 NSAID users, 373 controls, and 71 taking other analgesics. NSAID use was associated with higher executive function scores for cognitively normal (NL) subjects as well as subjects with mild cognitive impairment (MCI). NSAID use was also associated with higher memory scores, but for NL females only. We analysed MRI data using principal component analysis to generate a set of five EVs. Examining NL and MCI subjects, one EV had significantly larger values in subjects taking NSAIDs versus control. This EV was one of two EVs which significantly correlated with composite executive function and memory scores as well as cognitive diagnosis. Conclusions NSAID use was associated with higher executive function, and memory scores in certain subjects and larger cortical volumes in particular regions. Limitations of the study include secondary analysis of existing data and the possibility of confounding. Implications These results suggest it is important to consider the secondary effects of medications when choosing a treatment regimen. Further prospective studies are needed to examine the role of analgesics on cognition and whether NSAIDs act through cortical dimension changes and how they are related to gender and cognitive diagnosis.