Ian Carroll

Management of perioperative pain in patients chronically consuming opioids

Background The prevalence of licit and illicit opioid use is growing, and a greater percentage of chronically opioid-consuming patients are presenting for surgery. These patients can be expected to experience increased postoperative pain, greater postoperative opioid consumption, and prolonged use of healthcare resources for managing their pain. Methods Achieving adequate pain control in these patients can be challenging because commonly used strategies for alleviating postoperative pain may have diminished effectiveness. We explore the prevalence and characteristics of opioid use in the United States and discuss its impact on the perioperative management of pain. We examine mechanistically why adequate perioperative pain control in chronically opioid-consuming patients may be difficult. Conclusions We present strategies for providing adequate analgesia to these patients that include the optimal use of opioids, adjuvant medications, and regional anesthetic techniques.

Prenatal Diagnosis of Placenta Accreta Sonography or Magnetic Resonance Imaging

Objective. The purpose of this study was to compare the accuracy of transabdominal sonography and magnetic resonance imaging (MRI) for prenatal diagnosis of placenta accreta. Methods. A historical cohort study was undertaken at 3 institutions identifying women at risk for placenta accreta who had undergone both sonography and MRI prenatally. Sonographic and MRI findings were compared with the final diagnosis as determined at delivery and by pathologic examination. Results. Thirty‐two patients who had both sonography and MRI prenatally to evaluate for placenta accreta were identified. Of these, 15 had confirmation of placenta accreta at delivery. Sonography correctly identified the presence of placenta accreta in 14 of 15 patients (93% sensitivity; 95% confidence interval [CI], 80%–100%) and the absence of placenta accreta in 12 of 17 patients (71% specificity; 95% CI, 49%–93%). Magnetic resonance imaging correctly identified the presence of placenta accreta in 12 of 15 patients (80% sensitivity; 95% CI, 60%–100%) and the absence of placenta accreta in 11 of 17 patients (65% specificity; 95% CI, 42%–88%). In 7 of 32 cases, sonography and MRI had discordant diagnoses: sonography was correct in 5 cases, and MRI was correct in 2. There was no statistical difference in sensitivity (P = .25) or specificity (P = .5) between sonography and MRI. Conclusions. Both sonography and MRI have fairly good sensitivity for prenatal diagnosis of placenta accreta; however, specificity does not appear to be as good as reported in other studies. In the case of inconclusive findings with one imaging modality, the other modality may be useful for clarifying the diagnosis.

Perioperative gabapentinoids: choice of agent, dose, timing, and effects on chronic postsurgical pain.

1215 November 2013 T gabapentinoids pregabalin and gabapentin are both indicated for the treatment of postherpetic neuralgia and as adjuvant therapy for seizure disorders. Pregabalin is additionally approved for the treatment of fibromyalgia and neuropathic pain associated with diabetes mellitus or spinal cord injury. There are now more than 100 clinical trials examining the use of gabapentin perioperatively to reduce postoperative pain and a smaller but growing number of clinical trials examining the efficacy of pregabalin. As a body of work, they support the conclusion that perioperative use of gabapentinoids reduces early postoperative pain and opioid use.1–3 This article describes how this body of work may inform a surgeon’s or anesthesiologist’s optimization of perioperative use of gabapentinoids, including choice of agent, dose, timing, and duration of therapy. In addition, we described the less clear data for and against gabapentinoid efficacy in preventing the emergence of chronic postsurgical pain. Mechanisms of Action, Pharmacokinetics, and Adverse Effects Although both of the gabapentinoids are structural analogs of γ-aminobutyric acid, neither has any activity at the γ-aminobutyric acid receptors (fig. 1). Instead, they bind to the α-2δ subunit of presynaptic P/Q-type voltage-gated calcium channels, modulating the traffic and function of these channels. This in turn is thought to modulate the subsequent release of excitatory neurotransmitters from activated nociceptors.4 By modulating calcium-induced release of glutamate from activated pain-transmitting neurons, these drugs may inhibit pain transmission and central sensitization (fig. 2). Alternatively, some evidence indicates that their antinociceptive mechanism may arise through activation of noradrenergic pain-inhibiting pathways in the spinal cord and brain.5 The principal differences between these two drugs arise not from different modes of action but rather from differing bioavailability. Although both drugs are absorbed by amino acid carriers, gabapentin absorption is limited to a relatively small part of the duodenum, whereas pregabalin is absorbed throughout the small intestine. Once the active transport of gabapentin in the duodenum is saturated, progressively higher levels of gabapentin ingestion yield progressively smaller increases in blood concentrations. Conceptually, this provides an upper border not only to efficacy but also to adverse effects. In contrast, pregabalin appears to be absorbed throughout the small intestines and demonstrates linear uptake without transporter saturation at therapeutic concentrations.6,7 Therefore, at least conceptually, pregabalin might demonstrate both increased efficacy and increased side effects in situations that require high doses. Both pregabalin and gabapentin exhibit minimal protein binding and are renally excreted without significant metabolism. Pharmacokinetic interactions are minimal, though gabapentin absorption can be significantly impaired by antacids, even when given up to 2 h after dosing. This should be considered in preoperative Copyright

Sympathetic block with botulinum toxin to treat complex regional pain syndrome

Complex regional pain syndrome is a refractory pain condition with few tested therapies. We hypothesized that botulinum toxin A (BTA) would prolong analgesia after sympathetic blocks in patients with complex regional pain syndrome. We compared the duration of standard lumbar sympathetic block (LSB) with bupivacaine to LSB with bupivacaine and BTA in nine patients with refractory complex regional pain syndrome. Median time to analgesic failure was 71 (95% confidence interval, 12–253) days after LSB with BTA compared with fewer than 10 days (95% confidence interval, 0–12) after standard LSB (log‐rank, p < 0.02). BTA profoundly prolonged the analgesia from sympathetic block in this preliminary study. Ann Neurol 2009;65:348–351

A pilot cohort study of the determinants of longitudinal opioid use after surgery.

BACKGROUND: Determinants of the duration of opioid use after surgery have not been reported. We hypothesized that both preoperative psychological distress and substance abuse would predict more prolonged opioid use after surgery. METHODS: Between January 2007 and April 2009, a prospective, longitudinal inception cohort study enrolled 109 of 134 consecutively approached patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured the daily use of opioids until patients reported the cessation of both opioid consumption and pain. The primary end point was time to opioid cessation. All analyses were controlled for the type of surgery done. RESULTS: Overall, 6% of patients continued on new opioids 150 days after surgery. Preoperative prescribed opioid use, depressive symptoms, and increased self-perceived risk of addiction were each independently associated with more prolonged opioid use. Preoperative prescribed opioid use was associated with a 73% (95% confidence interval [CI] 0.51%–87%) reduction in the rate of opioid cessation after surgery (P = 0.0009). Additionally, each 1-point increase (on a 4-point scale) of self-perceived risk of addiction was associated with a 53% (95% CI 23%–71%) reduction in the rate of opioid cessation (P = 0.003). Independent of preoperative opioid use and self-perceived risk of addiction, each 10-point increase on a preoperative Beck Depression Inventory II was associated with a 42% (95% CI 18%–58%) reduction in the rate of opioid cessation (P = 0.002). The variance in the duration of postoperative opioid use was better predicted by preoperative prescribed opioid use, self-perceived risk of addiction, and depressive symptoms than postoperative pain duration or severity. CONCLUSIONS: Preoperative factors, including legitimate prescribed opioid use, self-perceived risk of addiction, and depressive symptoms each independently predicted more prolonged opioid use after surgery. Each of these factors was a better predictor of prolonged opioid use than postoperative pain duration or severity.

Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology

BackgroundChronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.MethodsTherefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.ResultsSelf-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.ConclusionsOur results support the role of cytokines in the pathophysiology of CFS.

Urinalysis vs urine protein–creatinine ratio to predict significant proteinuria in pregnancy

Objective: To compare the urine protein–creatinine ratio with urinalysis to predict significant proteinuria (⩾300 mg per day).Study Design: A total of 116 paired spot urine samples and 24-h urine collections were obtained prospectively from women at risk for preeclampsia. Urine protein–creatinine ratio and urinalysis were compared to the 24-h urine collection.Result: The urine protein–creatinine ratio had better discriminatory power than urinalysis: the receiver operating characteristic curve had a greater area under the curve, 0.89 (95% confidence interval (CI) 0.83 to 0.95) vs 0.71 (95% CI 0.64 to 0.77, P<0.001). When matched for clinically relevant specificity, urine protein–creatinine ratio (cutoff ⩾0.28) is more sensitive than urinalysis (cutoff ⩾1+): 66 vs 41%, P=0.001 (with 95 and 100% specificity, respectively). Furthermore, the urine protein–creatinine ratio predicted the absence or presence of proteinuria in 64% of patients; urinalysis predicted this in only 19%.Conclusion: The urine protein–creatinine ratio is a better screening test. It provides early information for more patients.

A Novel CT-Guided Transpsoas Approach to Diagnostic Genitofemoral Nerve Block and Ablation

BACKGROUND Inguinal hernia repair is associated with a high incidence of chronic postsurgical pain. This pain may be caused by injury to the iliohypogastric, ilioinguinal, or genitofemoral nerves. It is often difficult to identify the specific source of the pain, in part, because these nerves are derived from overlapping nerve roots and closely colocalize in the area of surgery. It is therefore technically difficult to selectively block these nerves individually proximal to the site of surgical injury. In particular, the genitofemoral nerve is retroperitoneal before entering the inguinal canal, a position that puts anterior approaches to the proximal nerve at risk of transgressing into the peritoneum. We report a computed tomography (CT)-guided transpsoas technique to selectively block the genitofemoral nerve for both diagnostic and therapeutic purposes while avoiding injury to the nearby ureter and intestines. CASE A 39-year-old woman with chronic lancinating right groin pain after inguinal hernia repair underwent multiple pharmacologic interventions and invasive procedures without relief. Using CT and Stimuplex nerve stimulator guidance, the genitofemoral nerve was localized on the anterior surface of the psoas muscle and a diagnostic block with local anesthetic block was performed. The patient had immediate relief of her symptoms for 36 hours, confirming the diagnosis of genitofemoral neuralgia. She subsequently underwent CT-guided radiofrequency and phenol ablation of the genitofemoral nerve but has not achieved long-term analgesia. CONCLUSION CT-guided transpsoas genitofemoral nerve block is a viable option for safely and selectively blocking the genitofemoral nerve for diagnostic or therapeutic purposes proximal to injury caused by inguinal surgery.

Reduced Cold Pain Tolerance in Chronic Pain Patients Following Opioid Detoxification

OBJECTIVE One potential consequence of chronic opioid analgesic administration is a paradoxical increase of pain sensitivity over time. Little scientific attention has been given to how cessation of opioid medication affects the hyperalgesic state. In this study, we examined the effects of opioid tapering on pain sensitivity in chronic pain patients. DESIGN Twelve chronic pain patients on long-term opioid analgesic treatment were observed in a 7- to 14-day inpatient pain rehabilitation program, with cold pain tolerance assessed at admission and discharge. The majority of participants were completely withdrawn from their opioids during their stay. OUTCOME MEASURES We hypothesized that those patients with the greatest reduction in daily opioid use would show the greatest increases in pain tolerance, as assessed by a cold pressor task. RESULTS A linear regression revealed that the amount of opioid medication withdrawn was a significant predictor of pain tolerance changes, but not in the direction hypothesized. Greater opioid reduction was associated with decreased pain tolerance. This reduction of pain tolerance was not associated with opioid withdrawal symptoms or changes in general pain. CONCLUSIONS These findings suggest that the withdrawal of opioids in a chronic pain sample leads to an acute increase in pain sensitivity.

Multivariate Analysis of Chronic Pain Patients Undergoing Lidocaine Infusions: Increasing Pain Severity and Advancing Age Predict Likelihood of Clinically Meaningful Analgesia

ObjectivesThe proportion of chronic pain patients with suspected neuropathic pain who will have clinically meaningful pain relief with intravenous (IV) lidocaine and the clinical characteristics that identify these patients have not been described previously. MethodsWe conducted a cohort study of 99 patients who underwent IV lidocaine infusions for suspected neuropathic pain. An 11-point Numerical Rating Score (NRS) of pain intensity was recorded at the beginning and end of each infusion. A predefined literature-based criteria for “clinically meaningful” reductions in pain score was used to classify patients as responders or nonresponders. Multivariate logistic regression was used to determine clinical variables that predicted an increased likelihood of being a lidocaine responder. ResultsThe mean reduction in NRS during lidocaine infusions was 2.34 (95% confidence interval 2.83-1.85, P<0.001). Forty-two percent of patients (95% confidence interval 32.5%-52.8%) had NRS reductions of 30% or greater and met the predefined criteria as lidocaine responders. Univariate and multivariate analyses indicated that advancing age and pain severity significantly increased the odds of being a lidocaine responder. Controlled for all other factors, each decade of advancing age increased the odds of being a lidocaine responder by 36%. Each 1-point increase, on an 11-point scale of baseline pain severity, increased the odds of being a lidocaine responder by 29%. DiscussionIV lidocaine effectively reduces pain in a minority of patients suspected of having neuropathic pain. Pain severity and patient age can be used to target therapy to those most likely to respond.