Ketamine and Cognitive Behavioral Therapy for Rapid Opioid Tapering With Sustained Opioid Abstinence: A Case Report and 1-Year Follow-up.

BACKGROUND: Ketamine, a potent analgesic and N-methyl-D-aspartate-(NMDA)-receptor antagonist, improves analgesic outcomes in patients with complex regional pain syndrome (CRPS). The NMDA receptor has also been implicated in opioid withdrawal. The use of ketamine to assist with a rapid opioid taper in the setting of CRPS has not been previously described. CASE: We present a case in which a 5-day continuous ketamine infusion was utilized in a robust multimodal analgesia regimen in combination with cognitive behavioral therapy (CBT) to successfully taper a patient with complex regional pain syndrome (CRPS) who was taking 330 mg of daily morphine equivalents completely off of opioids, minimize withdrawal symptoms, and produce sustained results. DISCUSSION: CRPS may involve catecholamine hypersensitivity and central sensitization and can be notoriously challenging to treat by itself even outside of the context of an opioid taper. The patient we describe here received one additional 5-day infusion at 6 months and remained opioid-free while experiencing a major improvement in function and lifestyle that he still maintains. This was possible through a combination of aggressive inpatient management with ketamine as the centerpiece, followed by consistent outpatient CBT to maintain results without the need for a return to opioids. This combination has previously not been described in the setting of a rapid opioid taper and this patient's underlying CRPS made it all the more remarkable.

Bypass of an anesthesiologist-directed preoperative evaluation clinic results in greater first-case tardiness and turnover times.

STUDY OBJECTIVE: We evaluated 4 hypotheses related to bypass of an anesthesiologist-directed preoperative evaluation clinics (APEC): 1) first-case tardiness and turnover times increased; 2) turnover times increased more than first-case tardiness; and higher American Society of Anesthesiologists Physical Status (ASA PS) resulted in both an ordered increase among ASA PS and within ASA PS in 3) first-case tardiness; and 4) turnover times. DESIGN: Retrospective observational study using electronic health records. SETTING: One large, teaching hospital. PATIENTS: An average of 14,310 patients per year undergoing elective surgery in the hospital's main opera rating rooms who were not inpatients preoperatively between 2006 and 2016. INTERVENTIONS: None. MEASUREMENTS: Average increases in first-case tardiness and turnover times between patients seen or not seen preoperatively in the APEC. MAIN RESULTS: APEC bypass increased first-case tardiness 2.58 min per case (CI 1.55-3.61; P<0.0001) and turnover times by 7.49 min (CI 6.79-8.19; P<0.0001). The increase in mean turnover time was greater than mean first-case tardiness (difference=4.91 min; CI 3.76-6.06; P<0.0001). Had all patients bypassed the APEC, the increase in total minutes OR- 1 workday- 1 for turnover times would have been larger than the increase in first-case tardiness (difference=5.71, CI 3.17-4.72; P<0.0001). There was an ordered increase with APEC bypass for both first-case tardiness and turnover times with increasing ASA PS (P<0.0001). Within ASA PS, first-case tardiness (all P-values<0.003) and turnover times (all P-values<0.0001) also increased with APEC bypass. All 4 hypotheses were accepted. CONCLUSIONS: Overall and with control for ASA PS, APEC bypass increases first-case tardiness and turnover times. A strategy of selective bypass of ASA PS 1-2 patients would not be effective economically because of substantial delays from ASA PS 2 patients.

Dynamics of the cognitive procedural learning in alcoholics with Korsakoff's syndrome.

BACKGROUND: While procedures acquired before the development of amnesia are likely to be preserved in alcoholic patients with Korsakoff's syndrome, the ability of Korsakoff patients (KS) to learn new cognitive procedures is called in question. According to the Adaptive Control of Thoughts model, learning a new cognitive procedure requires highly controlled processes in the initial cognitive phase, which may be difficult for KS with episodic and working memory deficits. The goals of the present study were to examine the learning dynamics of KS compared with uncomplicated alcoholic patients (AL) and control subjects (CS) and to determine the contribution of episodic and working memory abilities in cognitive procedural learning performance. METHODS: Fourteen KS, 15 AL, and 15 CS were submitted to 40 trials (4 daily learning sessions) of the Tower of Toronto task (disk-transfer task similar to the tower of Hanoi task) as well as episodic and working memory tasks. RESULTS: The 10 KS who were able to perform the cognitive procedural learning task obtained lower results than both CS and AL. The cognitive phase was longer in the Korsakoff's syndrome group than in the other 2 groups but did not differ between the 3 groups any more when episodic memory abilities were controlled. CONCLUSIONS: Our results indicate that KS have impaired cognitive procedural learning abilities compared with both AL and CS. Episodic memory deficits observed in KS result in a delayed transition from the cognitive learning phase to more advanced learning phases and, as a consequence, in an absence of automation of the procedure within 40 trials.

The influence of membrane bound proteins on phase separation and coarsening in cell membranes.

A theoretical explanation of the existence of lipid rafts in cell membranes remains a topic of lively debate. Large, micrometer sized rafts are readily observed in artificial membranes and can be explained using thermodynamic models for phase separation and coarsening. In live cells such domains are not observed and various models are proposed to describe why the systems do not coarsen. We review these attempts critically and show within a phase field approach that membrane bound proteins have the potential to explain the different behaviour observed in vitro and in vivo. Large scale simulations are performed to compute scaling laws and size distribution functions under the influence of membrane bound proteins and to observe a significant slow down of the domain coarsening at longer times and a breakdown of the self-similarity of the size-distribution function.

Systematic criteria for type and screen based on procedure's probability of erythrocyte transfusion.

BACKGROUND: At many hospitals, the type and screen decision is guided by the hospital's maximum surgical blood order schedule, a document that includes for each scheduled (elective) surgical procedure a recommendation of whether a preoperative type and screen be performed. There is substantial heterogeneity in the scientific literature for how that decision should be made. METHODS: Anesthesia information management system data were retrieved from the 160,207 scheduled noncardiac cases in adults of 1,253 procedures at a hospital. RESULTS: Neither assuming a Poisson distribution of mean erythrocyte units transfused, nor grouping rare procedures into larger groups based on their anesthesia Current Procedural Terminology code, was reliable. In contrast, procedures could be defined to have minimal estimated blood loss (less than 50 ml) based on low incidence of transfusion and low incidence of the hemoglobin being checked preoperatively. Among these procedures, when the lower 95% confidence limit for erythrocyte transfusion was less than 5%, type and screen was shown to be unnecessary. The method was useful based on including multiple differences from the hospital's maximum surgical blood order schedule and clinicians' test ordering (greater than or equal to 29% fewer type and screen). Results were the same with a Bayesian random effects model. CONCLUSIONS: We validated a method to determine procedures on the maximum surgical blood order schedule for which type and screen was not indicated using the estimated blood losses and incidences of transfusion.

Forecasting preanesthesia clinic appointment duration from the electronic medical record medication list.

BACKGROUND: When scheduling clinic appointments, scheduling patients expected to have different visit durations for different minutes of time reduces patient waiting time and staff idle time. Maintaining an active medication list is an important (and, in the United States, required) component to the meaningful use of electronic medical records. We hypothesized that the count of medications from the medication list would be a better predictor of the time taken by a nurse practitioner to evaluate the patient preoperatively than the American Society of Anesthesiologists' (ASA) physical status and other demographic variables. METHODS: Using 69,654 preoperative visits, we obtained the number of different medications taken by the patient and demographic variables, including ASA physical status, ASA base units, and body mass index. For each independent variable, we applied transformations and calculated the Pearson correlation giving the largest correlation with the log(10) (duration), which followed a normal distribution. RESULTS: Only 18% of the patients had been evaluated previously at the preoperative facility, making use of the prior ASA physical status ineffective for forecasting. The number of medications was a more accurate predictor of appointment duration than any of the other 8 variables (each Bonferroni corrected P < 0.0001), including ASA physical status. CONCLUSIONS: Schedulers can use the number of medications that each patient is taking when choosing the time for preoperative evaluation. This approach can take schedulers only approximately 10 seconds extra per patient when scheduling the appointment.

Obstructive sleep apnea syndrome and postoperative complications: clinical use of the STOP-BANG questionnaire.

OBJECTIVE: To determine whether high risk scores on preoperative STOP-BANG (Snoring, Tiredness during daytime, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, Gender) questionnaires during preoperative evaluation correlated with a higher rate of complications of obstructive sleep apnea syndrome (OSAS). DESIGN: Historical cohort study. SETTING: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. PATIENTS: Adult patients undergoing elective surgery at a tertiary care center who were administered the STOP-BANG questionnaire for 3 consecutive days in May 2008. MAIN OUTCOME MEASURES: Number and types of complications. RESULTS: A total of 135 patients were included in the study, of whom 56 (41.5%) had high risk scores for OSAS. The mean (SD) age of patients was 57.9 (14.4) years; 60 (44.4%) were men. Patients at high risk of OSAS had a higher rate of postoperative complications compared with patients at low risk (19.6% vs 1.3%; P < .001). Age, American Society of Anesthesiologists class of 3 or higher, and obesity were associated with an increased risk of postoperative complications. On multivariate analysis, high risk of OSAS and American Society of Anesthesiologists class 3 or higher were associated with higher odds of complications. CONCLUSION: The STOP-BANG questionnaire is useful for preoperative identification of patients at higher than normal risk for surgical complications, probably because it identifies patients with occult OSAS.

Particles on curved surfaces: a dynamic approach by a phase-field-crystal model.

We present a dynamic model to study ordering of particles on arbitrary curved surfaces. Thereby the particles are represented as maxima in a density field and a surface partial differential equation for the density field is solved to the minimal energy configuration. We study annihilation of dislocations within the ordered system and premelting along grain-boundary scars. The obtained minimal energy configurations on a sphere are compared with existing results and scaling laws are computed for the number of excess dislocations as a function of system size.

New and emerging analgesics and analgesic technologies for acute pain management.

PURPOSE OF REVIEW: Recent advances in drug delivery technology have provided new means of delivering medications with improved efficacy and safety. This review details developments in drug delivery recently made available or in development with the potential to better deliver analgesia. RECENT FINDINGS: Patient-controlled analgesia of intravenous medications was a major advance in drug delivery technology that allowed opioids to be administered more effectively and more safely. Extension of this technology to medications not administered intravenously has further broadened therapeutic options in the treatment of acute pain. Improvements in sustained-release formulations and patient-controlled analgesia modalities that are not catheter-based confer the potential to deliver analgesia less invasively. Receptor-specific antagonists allow opioids to be administered with fewer untoward side effects. SUMMARY: New routes of administration allow familiar medications to be utilized with greater clinical efficacy. Elimination of the need for indwelling catheters may reduce both the frequency of analgesic gaps and catheter-related complications. Physicians need to be familiar with developments in drug delivery technologies to be able to effectively utilize analgesics as part of well designed multimodal regimens to bring effective and well tolerated analgesia to patients with acute pain.

How do Korsakoff patients learn new concepts?

The goal of the present investigation was to assess semantic learning in Korsakoff patients (KS), compared with uncomplicated alcoholics (AL) and control subjects (CS), taking the nature of the information to-be-learned and the episodic memory profiles of the three groups into account. Ten new complex concepts, each illustrated by a photo and composed of a label, a category and three features, were taught to 13 KS, 23 AL and 45 CS. When examined independently of the main experimental task, the two patients' groups presented episodic memory, working memory and executive impairments but episodic memory was more severely impaired in KS. Both AL and KS exhibited label learning deficits but KS were more severely impaired than AL. The episodic memory results were the main factor accounting for label learning performance when the three groups were pooled together. When examined within each group, the correlation was significant in CS and AL but not in KS. Only KS exhibited impaired category and feature learning results. Episodic memory did not account for category and feature learning performance. New label learning may be equivalent to that of proper names, requiring the involvement of episodic memory notably to arbitrarily associate a meaningless word with a specific identity. However, when episodic memory is severely impaired like in KS, an alternative neocortical learning route, bypassing episodic memory, may be invoked. Category and feature seem to be acquired independently of episodic memory. The specific impairment in category and feature learning in KS may therefore reflect a genuine deficit of semantic memory in Korsakoff's syndrome.

Episodic and working memory deficits in alcoholic Korsakoff patients: the continuity theory revisited.

BACKGROUND: The exact nature of episodic and working memory impairments in alcoholic Korsakoff patients (KS) remains unclear, as does the specificity of these neuropsychological deficits compared with those of non-Korsakoff alcoholics (AL). The goals of the present study were therefore to (1) specify the nature of episodic and working memory impairments in KS, (2) determine the specificity of the KS neuropsychological profile compared with the AL profile, and (3) observe the distribution of individual performances within the 2 patient groups. METHODS: We investigated episodic memory (encoding and retrieval abilities, contextual memory and state of consciousness associated with memories), the slave systems of working memory (phonological loop, visuospatial sketchpad and episodic buffer) and executive functions (inhibition, flexibility, updating and integration abilities) in 14 strictly selected KS, 40 AL and 55 control subjects (CS). RESULTS: Compared with CS, KS displayed impairments of episodic memory encoding and retrieval, contextual memory, recollection, the slave systems of working memory and executive functions. Although episodic memory was more severely impaired in KS than in AL, the single specificity of the KS profile was a disproportionately large encoding deficit. Apart from organizational and updating abilities, the slave systems of working memory and inhibition, flexibility and integration abilities were impaired to the same extent in both alcoholic groups. However, some KS were unable to complete the most difficult executive tasks. There was only a partial overlap of individual performances by KS and AL for episodic memory and a total mixture of the 2 groups for working memory. CONCLUSIONS: Korsakoff's syndrome encompasses impairments of the different episodic and working memory components. AL and KS displayed similar profiles of episodic and working memory deficits, in accordance with neuroimaging investigations showing similar patterns of brain damage in both alcoholic groups.

Genuine episodic memory deficits and executive dysfunctions in alcoholic subjects early in abstinence.

BACKGROUND: Chronic alcoholism is known to impair episodic memory function, but the specific nature of this impairment is still unclear. Moreover, it has never been established whether episodic memory deficit in alcoholism is an intrinsic memory deficit or whether it has an executive origin. Thus, the objectives are to specify which episodic memory processes are impaired early in abstinence from alcohol and to determine whether they should be regarded as genuine memory deficits or rather as the indirect consequences of executive impairments. METHODS: Forty recently detoxified alcoholic inpatients at alcohol entry treatment and 55 group-matched controls underwent a neuropsychological assessment of episodic memory and executive functions. The episodic memory evaluation consisted of 3 tasks complementing each other designed to measure the different episodic memory components (learning, storage, encoding and retrieval, contextual memory, and autonoetic consciousness) and 5 executive tasks testing capacities of organization, inhibition, flexibility, updating, and integration. RESULTS: Compared with control subjects, alcoholic patients presented impaired learning abilities, encoding processes, retrieval processes, contextual memory and autonoetic consciousness. However, there was no difference between the 2 groups regarding the storage capacities assessed by the rate of forgetting. Concerning executive functions, alcoholic subjects displayed deficits in each executive task used. Nevertheless, stepwise regression analyses showed that only performances on fluency tasks were significantly predictive of some of the episodic memory disorders (learning abilities for 40%, encoding processes for 20%, temporal memory for 21%, and state of consciousness associated with memories for 26%) in the alcoholic group. DISCUSSION: At alcohol treatment entry, alcoholic patients present genuine episodic memory deficits that cannot be regarded solely as the consequences of executive dysfunctions. These results are in accordance with neuroimaging findings showing hippocampal atrophy. Moreover, given the involvement of episodic memory and executive functions in alcohol treatment, these data could have clinical implications.

Effect of episodic and working memory impairments on semantic and cognitive procedural learning at alcohol treatment entry.

BACKGROUND: Chronic alcoholism is known to impair the functioning of episodic and working memory, which may consequently reduce the ability to learn complex novel information. Nevertheless, semantic and cognitive procedural learning have not been properly explored at alcohol treatment entry, despite its potential clinical relevance. The goal of the present study was therefore to determine whether alcoholic patients, immediately after the weaning phase, are cognitively able to acquire complex new knowledge, given their episodic and working memory deficits. METHODS: Twenty alcoholic inpatients with episodic memory and working memory deficits at alcohol treatment entry and a control group of 20 healthy subjects underwent a protocol of semantic acquisition and cognitive procedural learning. The semantic learning task consisted of the acquisition of 10 novel concepts, while subjects were administered the Tower of Toronto task to measure cognitive procedural learning. RESULTS: Analyses showed that although alcoholic subjects were able to acquire the category and features of the semantic concepts, albeit slowly, they presented impaired label learning. In the control group, executive functions and episodic memory predicted semantic learning in the first and second halves of the protocol, respectively. In addition to the cognitive processes involved in the learning strategies invoked by controls, alcoholic subjects seem to attempt to compensate for their impaired cognitive functions, invoking capacities of short-term passive storage. Regarding cognitive procedural learning, although the patients eventually achieved the same results as the controls, they failed to automate the procedure. Contrary to the control group, the alcoholic groups' learning performance was predicted by controlled cognitive functions throughout the protocol. CONCLUSION: At alcohol treatment entry, alcoholic patients with neuropsychological deficits have difficulty acquiring novel semantic and cognitive procedural knowledge. Compared with controls, they seem to use more costly learning strategies, which are nonetheless less efficient. These learning disabilities need to be considered when treatment requiring the acquisition of complex novel information is envisaged.

Which processes are involved in cognitive procedural learning?

Procedural memory is characterised by a relative resistance to pathology, making its assessment of the utmost importance. However, few studies have looked at the cognitive processes involved in cognitive procedural learning. In an initial experiment, we studied the role of different cognitive functions in massed cognitive procedural learning. Our results confirmed the existence of three separate learning phases and, for the first time, demonstrated the involvement of episodic memory and executive functions in the first learning phase. In a second experiment, we studied the effect of distributed learning conditions on the dynamics of procedural learning. This second study confirmed our results but showed that these conditions slow down the process of cognitive procedural learning. Our overall findings call into question the status of functionally autonomous memory system that is currently allotted to procedural memory, and suggest that the role of nonprocedural cognitive components should be taken into account in patient rehabilitation.