Chad M. Brummett

Perineural administration of dexmedetomidine in combination with bupivacaine enhances sensory and motor blockade in sciatic nerve block without inducing neurotoxicity in rat.

Background:The current study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade without causing nerve damage. Methods:Thirty-one adult Sprague-Dawley rats received bilateral sciatic nerve blocks with either 0.2 ml bupivacaine, 0.5%, and 0.5% bupivacaine plus 0.005% dexmedetomidine in the contralateral extremity, or 0.2 ml dexmedetomidine, 0.005%, and normal saline in the contralateral extremity. Sensory and motor function were assessed by a blinded investigator every 30 min until the return of normal sensory and motor function. Sciatic nerves were harvested at either 24 h or 14 days after injection and analyzed for perineural inflammation and nerve damage. Results:High-dose dexmedetomidine added to bupivacaine significantly enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did not cause significant motor or sensory block. All of the nerves analyzed had normal axons and myelin at 24 h and 14 days. Bupivacaine plus dexmedetomidine showed less perineural inflammation at 24 h than the bupivacaine group when compared with the saline control. Conclusion:The finding that high-dose dexmedetomidine can safely improve the duration of bupivacaine-induced antinociception after sciatic nerve blockade in rats is an essential first step encouraging future studies in humans. The dose of dexmedetomidine used in this study may exceed the sedative safety threshold in humans and could cause prolonged motor blockade; therefore, future work with clinically relevant doses is necessary.

Perioperative peripheral nerve injuries: a retrospective study of 380,680 cases during a 10-year period at a single institution.

Background:Peripheral nerve injuries represent a notable source of anesthetic complications and can be debilitating. The objective of this study was to identify associations with peripheral nerve injury in a broad surgical population cared for in the last decade. Methods:At a tertiary care university hospital, the quality assurance, closed claims, and institution-wide billing code databases were searched for peripheral nerve injuries over a 10-yr period. Each reported case was individually reviewed to determine whether a perioperative injury occurred, defined as a new sensory and/or motor deficit. The location and type of the injury were also identified. Nerve complications as a result of the surgical procedure itself were excluded, and an expert review panel assisted in the adjudication of unclear cases. Patient preoperative characteristics, anesthetic modality, and surgical specialty were evaluated for associations. Results:Of all patients undergoing 380,680 anesthetics during a 10-yr period, 185 patients were initially identified as having nerve injuries, and after review, 112 met our definition of a perioperative nerve injury (frequency = 0.03%). Hypertension, tobacco use, and diabetes mellitus were significantly associated with perioperative peripheral nerve injuries. General and epidural anesthesia were associated with nerve injuries. Significant associations were also found with the following surgical specialties: Neurosurgery, cardiac surgery, general surgery, and orthopedic surgery. Conclusions:To our knowledge, this is the largest number of consecutive patients ever reviewed for all types of perioperative peripheral nerve injuries. More importantly, this is the first study to identify associations of nerve injuries with hypertension, anesthetic modality, and surgical specialty.

New persistent opioid use after minor and major surgical procedures in us adults

Importance Despite increased focus on reducing opioid prescribing for long-term pain, little is known regarding the incidence and risk factors for persistent opioid use after surgery. Objective To determine the incidence of new persistent opioid use after minor and major surgical procedures. Design, Setting, and Participants Using a nationwide insurance claims data set from 2013 to 2014, we identified US adults aged 18 to 64 years without opioid use in the year prior to surgery (ie, no opioid prescription fulfillments from 12 months to 1 month prior to the procedure). For patients filling a perioperative opioid prescription, we calculated the incidence of persistent opioid use for more than 90 days among opioid-naive patients after both minor surgical procedures (ie, varicose vein removal, laparoscopic cholecystectomy, laparoscopic appendectomy, hemorrhoidectomy, thyroidectomy, transurethral prostate surgery, parathyroidectomy, and carpal tunnel) and major surgical procedures (ie, ventral incisional hernia repair, colectomy, reflux surgery, bariatric surgery, and hysterectomy). We then assessed data for patient-level predictors of persistent opioid use. Main Outcomes and Measures The primary outcome was defined a priori prior to data extraction. The primary outcome was new persistent opioid use, which was defined as an opioid prescription fulfillment between 90 and 180 days after the surgical procedure. Results A total of 36 177 patients met the inclusion criteria, with 29 068 (80.3%) receiving minor surgical procedures and 7109 (19.7%) receiving major procedures. The cohort had a mean (SD) age of 44.6 (11.9) years and was predominately female (23 913 [66.1%]) and white (26 091 [72.1%]). The rates of new persistent opioid use were similar between the 2 groups, ranging from 5.9% to 6.5%. By comparison, the incidence in the nonoperative control cohort was only 0.4%. Risk factors independently associated with new persistent opioid use included preoperative tobacco use (adjusted odds ratio [aOR], 1.35; 95% CI, 1.21-1.49), alcohol and substance abuse disorders (aOR, 1.34; 95% CI, 1.05-1.72), mood disorders (aOR, 1.15; 95% CI, 1.01-1.30), anxiety (aOR, 1.25; 95% CI, 1.10-1.42), and preoperative pain disorders (back pain: aOR, 1.57; 95% CI, 1.42-1.75; neck pain: aOR, 1.22; 95% CI, 1.07-1.39; arthritis: aOR, 1.56; 95% CI, 1.40-1.73; and centralized pain: aOR, 1.39; 95% CI, 1.26-1.54). Conclusions and Relevance New persistent opioid use after surgery is common and is not significantly different between minor and major surgical procedures but rather associated with behavioral and pain disorders. This suggests its use is not due to surgical pain but addressable patient-level predictors. New persistent opioid use represents a common but previously underappreciated surgical complication that warrants increased awareness.

Perineural dexmedetomidine added to ropivacaine for sciatic nerve block in rats prolongs the duration of analgesia by blocking the hyperpolarization-activated cation current.

Background: The current study was designed to test the hypothesis that the increased duration of analgesia caused by adding dexmedetomidine to local anesthetic results from blockade of the hyperpolarization-activated cation (Ih) current. Methods: In this randomized, blinded, controlled study, the analgesic effects of peripheral nerve blocks using 0.5% ropivacaine alone or 0.5% ropivacaine plus dexmedetomidine (34 &mgr;M or 6 &mgr;g/kg) were assessed with or without the pretreatment of &agr;1- and &agr;2-adrenoceptor antagonists (prazosin and idazoxan, respectively) and antagonists and agonists of the Ih current (ZD 7288 and forskolin, respectively). Sciatic nerve blocks were performed, and analgesia was measured by paw withdrawal latency to a thermal stimulus every 30 min for 300 min postblock. Results: The analgesic effect of dexmedetomidine added to ropivacaine was not reversed by either prazosin or idazoxan. There were no additive or attenuated effects from the pretreatment with ZD 7288 (Ih current blocker) compared with dexmedetomidine added to ropivacaine. When forskolin was administered as a pretreatment to ropivacaine plus dexmedetomidine, there were statistically significant reductions in duration of analgesia at time points 90–180 min (P < 0.0001 for each individual comparison). The duration of blockade for the forskolin (768 &mgr;M) followed by ropivacaine plus dexmedetomidine group mirrored the pattern of the ropivacaine alone group, thereby implying a reversal effect. Conclusion: Dexmedetomidine added to ropivacaine caused approximately a 75% increase in the duration of analgesia, which was reversed by pretreatment with an Ih current enhancer. The analgesic effect of dexmedetomidine was not reversed by an &agr;2-adrenoceptor antagonist.

Perineural Dexmedetomidine Added to Ropivacaine Causes a Dose-dependent Increase in the Duration of Thermal Antinociception in Sciatic Nerve Block in Rat

Background:The current study was designed to test the hypothesis that dexmedetomidine added to ropivacaine would increase the duration of antinociception to a thermal stimulus in a dose-dependent fashion in a rat model of sciatic nerve blockade. Methods:Fifty adult Sprague-Dawley rats (10 rats/group) received unilateral sciatic nerve blocks with 0.2 ml ropivacaine (0.5%) or 0.2 ml ropivacaine (0.5%) plus dexmedetomidine (2.7 &mgr;m [0.5 &mgr;g/kg], 11.7 &mgr;m [2 &mgr;g/kg], 34.1 &mgr;m [6 &mgr;g/kg], or 120.6 &mgr;m [20 &mgr;g/kg]) in a randomized, blinded fashion. Time to paw withdrawal latency to a thermal stimulus for both paws and an assessment of motor function were measured every 30 min after the nerve block until a return to baseline. Results:Dexmedetomidine added to ropivacaine increased the duration of dense sensory blockade and time for return to normal sensory function in a dose-dependent fashion (P < 0.005). There was a significant time (P < 0.005), dose (P < 0.005), and time-by-dose effect (P < 0.005) on paw withdrawal latencies of the operative paws. There were no significant differences in paw withdrawal latencies of the control paws, indicating little systemic effect of the dexmedetomidine. The duration of motor blockade was also increased with dexmedetomidine. High-dose dexmedetomidine (120.6 &mgr;m) was not neurotoxic. Conclusion:This is the first study showing that dexmedetomidine added to ropivacaine increases the duration of sensory blockade in a dose-dependent fashion in rats. The findings are an essential first step encouraging future efficacy studies in humans.

Survey Criteria for Fibromyalgia Independently Predict Increased Postoperative Opioid Consumption after Lower Extremity Joint Arthroplasty: A Prospective, Observational Cohort Study

Background:Variance in pain after total knee and hip arthroplasty may be due to a number of procedural and peripheral factors but also, in some individuals, to aberrant central pain processing as is described in conditions like fibromyalgia. To test this hypothesis, the authors conducted a prospective, observational cohort study of patients undergoing lower-extremity joint arthroplasty. Methods:Five hundred nineteen patients were preoperatively phenotyped using validated self-reported pain questionnaires, psychological measures, and health information. In addition to being assessed for factors previously found to be associated with poor outcomes in arthroplasty, participants also completed the American College of Rheumatology survey criteria for fibromyalgia. Previous studies have suggested that rather than being “present” or “absent,” features of fibromyalgia as measured by this instrument, occur over a wide continuum. Postoperative pain control was assessed by total postoperative opioid consumption. Results:Preoperatively, patients with higher fibromyalgia survey scores were younger, more likely to be female, taking more opioids, reported higher pain severity, and had a more negative psychological profile. In the multivariate analysis, the fibromyalgia survey score, younger age, preoperative opioid use, knee (vs. hip), pain severity at baseline, and the anesthetic technique were all predictive of increased postoperative opioid consumption. Conclusions:The use of the survey criteria for fibromyalgia led to the finding of distinct phenotypic differences, and the measure was independently predictive of opioid consumption. This self-report measure may provide an additional simple means of predicting postoperative pain outcomes and analgesic requirements. Future studies are needed to determine whether tailored therapies can improve postoperative pain control in this population.

Trends and predictors of opioid use after total knee and total hip arthroplasty.

Abstract Few studies have assessed postoperative trends in opioid cessation and predictors of persistent opioid use after total knee arthroplasty (TKA) and total hip arthroplasty (THA). Preoperatively, 574 TKA and THA patients completed validated, self-report measures of pain, functioning, and mood and were longitudinally assessed for 6 months after surgery. Among patients who were opioid naive the day of surgery, 8.2% of TKA and 4.3% of THA patients were using opioids at 6 months. In comparison, 53.3% of TKA and 34.7% of THA patients who reported opioid use the day of surgery continued to use opioids at 6 months. Patients taking >60 mg oral morphine equivalents preoperatively had an 80% likelihood of persistent use postoperatively. Day of surgery predictors for 6-month opioid use by opioid-naive patients included greater overall body pain (P = 0.002), greater affected joint pain (knee/hip) (P = 0.034), and greater catastrophizing (P = 0.010). For both opioid-naive and opioid users on the day of surgery, decreases in overall body pain from baseline to 6 months were associated with decreased odds of being on opioids at 6 months (adjusted odds ratio [aOR] = 0.72, P = 0.050; aOR = 0.62, P = 0.001); however, change in affected joint pain (knee/hip) was not predictive of opioid use (aOR = 0.99, P = 0.939; aOR = 1.00, P = 0.963). In conclusion, many patients taking opioids before surgery continue to use opioids after arthroplasty and some opioid-naive patients remained on opioids; however, persistent opioid use was not associated with change in joint pain. Given the growing concerns about chronic opioid use, the reasons for persistent opioid use and perioperative prescribing of opioids deserve further study.

The effect of opioid dose and treatment duration on the perception of a painful standardized clinical stimulus.

Background and Objectives: The concept of opioid‐induced hyperalgesia has recently gained prominence as a contributing factor for opioid tolerance and long‐term treatment failure. But whereas the preclinical data for this phenomenon are strong, the mixed clinical data derive primarily from experimental pain models conducted in volunteers and heroin addicts, and nonstandardized clinical stimuli, e.g., surgery. The primary objective of this study is to delineate the effect of opioid dose and treatment duration on pain intensity and unpleasantness ratings following a standardized clinical pain stimulus. Methods: Three hundred and fifty‐five patients, on a steady regimen of analgesic medications and scheduled for an interventional procedure, received a standardized subcutaneous injection of lidocaine prior to a full dose of local anesthetic. Before and immediately following the injection, subjects were asked to rate pain and unpleasantness intensity on a 0 to 10 numerical rating scale. Subjects were stratified into 6 groups based on opioid dosage. A control group of 27 volunteers who had no pain and were taking no analgesics were also injected. Results: Both opioid dose and duration of treatment directly correlated with pain intensity and unpleasantness scores. Baseline pain intensity was also positively associated with both outcome variables. Gender was found to be associated with pain intensity and unpleasantness, with females scoring higher in both categories than males. Compared with patients not receiving opioid treatment, patients receiving opioid therapy were more likely to rate the standardized pain stimulus as being more unpleasant than painful. Conclusions: The results of this study bolster preclinical and experimental pain models demonstrating enhanced pain perception in subjects receiving opioid therapy. This simple clinical model may provide a useful tool in examining opioid‐induced hyperalgesia.

Facet joint pain—advances in patient selection and treatment

Facetogenic pain, also known as zygapophysial joint pain, is a frequent cause of mechanical spine pain. Diagnostic blocks (for example, medial branch blocks [MBBs]) are the only reliable approach to identify facet joints as the source of neck or back pain. In the absence of a reference standard, MBBs actually serve more of a prognostic than diagnostic role, enabling the selection of patients who might respond to radiofrequency denervation treatment—the standard treatment for facet joint pain. Using double blocks reduces the false-positive rate of MBBs, but will invariably reduce the overall treatment success rate. No studies have evaluated non-interventional treatments for confirmed facetogenic pain, but data from studies in non-specific back pain suggest a modest, short-term beneficial effect for pharmacotherapy and some non-traditional treatments. Trials of intra-articular steroid injections for lumbar and cervical facet joint pain have yielded disappointing results, but evidence suggests that a subpopulation of patients with acute inflammation derive intermediate-term benefit from this therapy. Radiofrequency denervation provides some benefit for up to a year in approximately 60% of individuals. Increasing this success rate might involve enhancing diagnostic specificity and phenotyping, as well as techniques that increase the likelihood of successful nerve ablation, such as maximizing lesion size.

Fibromyalgia Survey Criteria Are Associated with Increased Postoperative Opioid Consumption in Women Undergoing Hysterectomy

Background: The current study was designed to test the hypothesis that the fibromyalgia survey criteria would be directly associated with increased opioid consumption after hysterectomy even when accounting for other factors previously described as being predictive for acute postoperative pain. Methods: Two hundred eight adult patients undergoing hysterectomy between October 2011 and December 2013 were phenotyped preoperatively with the use of validated self-reported questionnaires including the 2011 fibromyalgia survey criteria, measures of pain severity and descriptors, psychological measures, preoperative opioid use, and health information. The primary outcome was the total postoperative opioid consumption converted to oral morphine equivalents. Results: Higher fibromyalgia survey scores were significantly associated with worse preoperative pain characteristics, including higher pain severity, more neuropathic pain, greater psychological distress, and more preoperative opioid use. In a multivariate linear regression model, the fibromyalgia survey score was independently associated with increased postoperative opioid consumption, with an increase of 7-mg oral morphine equivalents for every 1-point increase on the 31-point measure (Estimate, 7.0; Standard Error, 1.7; P < 0.0001). In addition to the fibromyalgia survey score, multivariate analysis showed that more severe medical comorbidity, catastrophizing, laparotomy surgical approach, and preoperative opioid use were also predictive of increased postoperative opioid consumption. Conclusions: As was previously demonstrated in a total knee and hip arthroplasty cohort, this study demonstrated that increased fibromyalgia survey scores were predictive of postoperative opioid consumption in the posthysterectomy surgical population during their hospital stay. By demonstrating the generalizability in a second surgical cohort, these data suggest that patients with fibromyalgia-like characteristics may require a tailored perioperative analgesic regimen.