Postoperative Opioid Administration Research Articles

176. Thoracolumbar interfascial plane (TLIP) block and intrathecal fentanyl injection results in an opioid-free peri- and postoperative recovery and early ambulation after percutaneous lumbar spine surgery

BACKGROUND CONTEXT Open lumbar spine fusion surgery usually requires opioid analgesia for several weeks during the postoperative recovery period. Recently, a facet-sparing, full percutaneous transforaminal lumbar interbody fusion (TLIF) has been introduced that uses an endoscopic cannula for placement of an interbody cage in combination with percutaneous transpedicular screws and rods. The Thoraco-Lumbar Interfascial Plain (TLIP) block is a novel, ultrasound-guided local anesthesia technique that targets the sensory component of the dorsal rami of the thoracolumbar nerves. PURPOSE We aim to evaluate the efficacy in avoiding post-operative opioid analgesics and allowing early patient ambulation of a novel inter-disciplinary, spine surgery protocol that combines a perioperative TLIP block, intrathecal fentanyl injection and percutaneous TLIF spine surgery. STUDY DESIGN/SETTING Prospective, nonrandomized sequential case series study. PATIENT SAMPLE A total of 15 consecutive patients underwent TLIP combined with percutaneous TLIF spine surgery between 2018 and 2019. Indication for spine surgery was degenerative disk disease of the lumbar spine with or without spondylolisthesis up to grade 2 and foraminal stenosis. OUTCOME MEASURES Pre- and postoperative visual analogic scale (VAS) for lumbar back and leg pain were quantitatively assessed (range 0 to 10) immediately, at 6 and at 12 hours after surgery and at time of hospital discharge. Oswestry Disability Index (ODI) scores (range 0 to 50) were assessed preoperatively and at time of hospital discharge. The time of first post-operative patient ambulation was registered. Significance between pre- and postoperative scores were analyzed with student's paired t-test. METHODS Intrathecal fentanyl 25 mcgr was administered to the patient in sitting position and ultrasound-guided bilateral TLIP was performed in prone position with bupivacaine 0.25% and dexamethasone 8mgrs (20ml each side) by the anesthesia team. All patients were operated on under general anesthesia (protocol: propofol 2.0-3.0 mcg/ml (TCI) following BIS, ketamine 0.15 mg/Kg/h, rocuronium 0.4 mg/Kg). Percutaneous TLIF was performed by inserting an expandable interbody implant using the facet-sparing, trans-Kambin approach with an endoscopic cannula and complemented with a percutaneous posterior fixation consisting of transpedicular screws and rods. Postoperative analgesia included NSAIDs, acetaminophen and a manually patient-controlled oral sublingual 15 mcgr sufentanil microtablet analgesic system (Zalviso®), while its use was monitored. RESULTS Fifteen patients with a mean age of 64.1 years (range, 34 to 82 years) were evaluated. A median of two levels (range, 1 to 4 levels) per patient were instrumented and a median of one interbody cage (range, 1 to 2 cages) was placed in the lumbar spine. No intravenous fentanyl administration was necessary during surgery. The median time of surgery was 3.5 hours. Mean preoperative VAS scores for lumbar back and leg pain were 6.3 and 5.8, respectively. Mean postoperative VAS back scores at 0h, 6h, 12h and at discharge improved to 1.2, 1.8, 2.4 and 2.7 (P CONCLUSIONS The combination of perioperative TLIP, intrathecal fentanyl injection and percutaneous TLIF surgery prevents peri- and postoperative opioid administration and improves the quality of peri- and postoperative analgesia, allowing early patient ambulation and fast hospital discharge. This interdisciplinary analgesia protocol is a promising solution to avoid opioid analgesia in spine surgery and could be particularly interesting in the context of an outpatient spine surgery setting. FDA DEVICE/DRUG STATUS Fentanyl (Approved for this indication), Zalviso (Approved for this indication), Bupivacaine (Approved for this indication), Globus RISE (Approved for this indication)

Arthroscopic capsular release and continuous upper arm brachial block in frozen shoulder – A midterm outcome analysis

ObjectiveThis prospective study aims to evaluate the efficacy of Continuous upper arm brachial block (modified interscalene block) with an arthroscopic capsular release in the outcome of resistant frozen shoulder cases. MethodsWe studied 123 patients who underwent arthroscopic capsular release and subacromial decompression for resistant frozen shoulder cases between June 2016 and July 2019. Postoperative analgesia was provided with Continuous upper arm brachial block and ambulatory patient-controlled analgesia pump for 2–3 weeks. The patients were started on regular physiotherapy on the first postoperative day. All the patients were followed up at 3rd week, 6th week, 3rdmonth, 6th month, 1st year, and 2nd year with VAS and Constant-Murley scores. ResultsAt a mean follow-up period of 18 months, there was a statistically significant improvement in the range of motion, VAS scores, and Constant-Murley scores postoperatively (p < .01). None of the cases required postoperative opioid administration for pain control. Minor neurological complications like recurrent laryngeal nerve palsy and Horner's syndrome were seen in few cases that resolved with titration of the drug dose. ConclusionOur study verifies the use of continuous upper arm brachial block (CUABB) with a portable infusion pump for 2–3 weeks in arthroscopic capsular release for resistant frozen shoulder cases. It significantly reduced postoperative pain in the initial two weeks that aided with early recovery of the shoulder movements and functions without an increased incidence of acute or chronic neurologic complications.

Benefits of robotic cystectomy compared with open cystectomy in an Enhanced Recovery After Surgery program: A propensity-matched analysis.

To compare the perioperative and oncological outcomes between robot-assisted radical cystectomy with intracorporeal urinary diversion versus open cystectomy for bladder cancer in a contemporary Enhanced Recovery After Surgery cohort. All consecutive patients who underwent radical cystectomy and managed under an Enhanced Recovery After Surgery protocol, from December 2013 to October 2018, were reviewed. Propensity score adjustment was carried out to reduce biases attributable to covariate imbalances. There were 19 robot-assisted radical cystectomy with intracorporeal urinary diversion and 21 open cystectomy patients. The robot-assisted radical cystectomy with intracorporeal urinary diversion cohort was associated with lower estimated blood loss (397 vs 787mL, P=0.05), with a trend toward shorter duration of ileus and postoperative opioid administration. These benefits were apparent, despite a longer operative time (581 vs 446 mins, P=0.03), a higher proportion of orthotopic bladder reconstruction (26.3 vs 9.5%, P=0.08), a more prevalent use of neoadjuvant chemotherapy and a higher number of salvage cystectomies for the robot-assisted radical cystectomy with intracorporeal urinary diversion group. Comparable perioperative complications and length of hospital stay were observed. The pathological and intermediate oncological outcomes were similar in both groups (locally advanced disease: 52.6 vs 47.6%, P=0.85; lymph node yield: 29 vs 34, P=0.23). The mean recurrence-free survival and overall survival in the robot-assisted radical cystectomy with intracorporeal urinary diversion group was 37.5 and 43.0months, respectively, compared with 21.4 (P=0.09) and 35.5 (P=0.14) months, respectively, in open cystectomy. Robot-assisted radical cystectomy with intracorporeal urinary diversion has perioperative benefits of lower estimated blood loss, with a trend toward faster bowel recovery and a shorter duration of opioid analgesia when compared with open cystectomy. Robot-assisted radical cystectomy with intracorporeal urinary diversion also achieves similar intermediate-term oncological and survival outcomes.

Perioperative Prescribing Practices of Extended-Release Opioids in Noncancer Surgical Patients, 2015-2018.

Extended-release (ER) opioids are indicated for the management of persistent moderate to severe pain in patients requiring around-the-clock opioid analgesics for an extended period of time. Concerns have been raised regarding safety of ER opioids due to its potential for abuse and dependence. However, little is known about perioperative prescribing practices of ER opioids. This study assessed perioperative prescribing practices of ER opioids in noncancer surgical patients stratified by type of opioid exposure prior to admission and examined predictors of postoperative opioid administration in oral morphine equivalents (OME). This was a retrospective cohort study using the University of California San Francisco Medical Center electronic health record data. This study included 25,396 adult noncancer patients undergoing elective surgery under general anesthesia in the period 2015-2018. The primary study outcome was predictors of postoperative administration of opioids in hospitalized surgical patients. Secondary outcomes included patients discontinued and initiated on ER opioids during their hospital stay. substance use disorder diagnosis and use of opioids, surgery type, and postoperative administration of nonopioid analgesics were associated with postoperative administration of opioids (P < .0001). The estimated adjusted mean (95% confidence interval [CI]) of postoperative administration of OME prior to admission in ER opioid users (170.08 mg; 147.08-196.67) was twice the amount for opioid-naïve patients (81.36 mg; 70.7-93.63; P < .0001). One in 5 prior to admission ER opioid users were weaned off ER opioids while hospitalized without adversely affecting their postoperative pain or hospital length of stay (LOS). Four of 5 patients who used ER opioids prior to admission also received ER opioids after surgery, whereas, 1 in 100 opioid-naïve patients received ER opioids during their hospital stay. We found significant variability in the perioperative prescribing practices of ER opioids in hospitalized noncancer surgical patients by use of opioids prior to admission and surgery type. Pain medicine practitioners and surgeons may play a significant role tackling the surgery-related risk of exposure to ER opioids and decreasing opioid-related complications.

Combined spinal epidural for labour analgesia and caesarean section: indications and recommendations.

Even if its use is scarce in most countries, many articles concerning combined spinal epidural (CSE) were published. In this review, we present the latest advances concerning CSE in obstetrics. During labour, CSE improves epidural analgesia quality. Epidural with intradural opioids can produce maternal hypotension and foetal heart rate abnormalities (FHR-Ab), without increasing the caesarean section rate. For caesarean section, CSE decreases the neuraxial block failure rate, with no significant increase of complications. Epidural volume extension (EVE) after CSE for caesarean section could be an interesting option even though more evidence is needed. For labour analgesia, CSE has the fastest onset time of analgesia. Its side effects have no consequences on maternal, labour or foetal outcomes. It provides better analgesia than epidural analgesia and can be used for external cephalic version and high-risk patients. For caesarean section, CSE has become the reference neuraxial technique for low-dose spinal anaesthesia, with higher success rate compared with regular spinal anaesthesia. Recent systematic revisions did not confirm this superiority. CSE offers the advantage of EVE, intraoperative top-ups, postoperative administration of neuraxial opioids and local anaesthetics. The risk of complications is balanced by the benefits of the technique.

Preoperative albumin levels predict prolonged postoperative ileus in gastrointestinal surgery.

BACKGROUNDProlonged postoperative ileus (PPOI) is a prolonged state of “pathological” gastrointestinal (GI) tract dysmotility. There are relatively few studies examining the influence of preoperative nutritional status on the development of PPOI in patients who underwent GI surgery. The association between preoperative albumin and PPOI has not been fully studied. We hypothesized that preoperative albumin may be an independent indicator of PPOI.AIMTo analyze the role of preoperative albumin in predicting PPOI and to establish a nomogram for clinical risk evaluation.METHODSPatients were drawn from a prospective hospital registry database of GI surgery. A total of 311 patients diagnosed with gastric or colorectal cancer between June 2016 and March 2017 were included. Potential predictors of PPOI were analyzed by univariate and multivariable logistic regression analyses, and a nomogram for quantifying the presence of PPOI was developed and internally validated.RESULTSThe overall PPOI rate was 21.54%. Advanced tumor stage and postoperative opioid analgesic administration were associated with PPOI. Preoperative albumin was an independent predictor of PPOI, and an optimal cutoff value of 39.15 was statistically calculated. After adjusting multiple variables, per unit or per SD increase in albumin resulted in a significant decrease in the incidence of PPOI of 8% (OR = 0.92, 95%CI: 0.85-1.00, P = 0.046) or 27% (OR = 0.73, 95%CI: 0.54-0.99, P = 0.046), respectively. Patients with a high level of preoperative albumin (≥ 39.15) tended to experience PPOI compared to those with low levels (< 39.15) (OR = 0.43, 95%CI: 0.24-0.78, P = 0.006). A nomogram for predicting PPOI was developed [area under the curve (AUC) = 0.741] and internally validated by bootstrap resampling (AUC = 0.725, 95%CI: 0.663-0.799).CONCLUSIONPreoperative albumin is an independent predictive factor of PPOI in patients who underwent GI surgery. The nomogram provided a model to screen for early indications in the clinical setting.

The Reducing Opioid Use in Children with Clefts Protocol: A Multidisciplinary Quality Improvement Effort to Reduce Perioperative Opioid Use in Patients Undergoing Cleft Surgery.

Cleft repair requires multiple operations from infancy through adolescence, with repeated exposure to opioids and their associated risks. The authors implemented a quality improvement project to reduce perioperative opioid exposure in their cleft lip/palate population. After identifying key drivers of perioperative opioid administration, quality improvement interventions were developed to address these key drivers and reduce postoperative opioid administration from 0.30 mg/kg of morphine equivalents to 0.20 mg/kg of morphine equivalents. Data were retrospectively collected from January 1, 2015, until initiation of the quality improvement project (May 1, 2017), tracked over the 6-month quality improvement study period, and the subsequent 14 months. Metrics included morphine equivalents of opioids received during admission, administration of intraoperative nerve blocks, adherence to revised electronic medical record order sets, length of stay, and pain scores. The final sample included 624 patients. Before implementation (n =354), children received an average of 0.30 mg/kg of morphine equivalents postoperatively. After implementation (n = 270), children received an average of 0.14 mg/kg of morphine equivalents postoperatively (p < 0.001) without increased length of stay (28.3 versus 28.7 hours; p = 0.719) or pain at less than 6 hours (1.78 versus 1.74; p = 0.626) or more than 6 hours postoperatively (1.50 versus 1.49; p = 0.924). Perioperative opioid administration after cleft repair can be reduced in a relatively short period by identifying key drivers and addressing perioperative education, standardization of intraoperative pain control, and postoperative prioritization of nonopioid medications and nonpharmacologic pain control. The authors' quality improvement framework has promise for adaptation in future efforts to reduce opioid use in other surgical patient populations. Therapeutic, III.

The effect of preemptive use of pregabalin on postoperative morphine consumption and analgesia levels after laparoscopic colorectal surgery: a controlled randomized trial.

In order to reduce postoperative opioid administration and pain levels in patients submitted to laparoscopic colectomy, we assessed the efficacy of preemptive use of pregabalin (PG), as part of a multimodal analgesia scheme, in a randomized controlled trial setting. Overall, fifty adult patients scheduled for elective laparoscopic colectomy were included and randomized in our trial. In the experimental group, 23 patients received preoperatively 2 doses of 150mg PG per os, whereas the control group consisted of 27 cases, where a matching to PG placebo was administered at the same scheme. The two groups had identical analgesia and anesthesia regimens otherwise. Our study endpoints included postoperative morphine consumption, postoperative pain, and complication rates. Patients in the PG group displayed a significantly reduced morphine consumption at 8h, 24h, and 48h postoperatively. The two groups were comparable in terms of postoperative pain (rest and movement assessment) and side effects. The preoperative addition of PG resulted in a significant reduction of the postoperative opioid consumption in patients undergoing laparoscopic colectomy. However, an association with the postoperative pain scores was not identified.

Effects of quadratus lumborum block regional anesthesia on postoperative pain after colorectal resection: a randomized controlled trial.

Postoperative pain following colorectal surgery is associated with a significant use of opioids. Recently, regional anesthesia, such as the posterior quadratus lumborum block (QL2), has been proposed to improve pain relief and reduce opioid use. However, the benefit of the QL2 on postoperative pain control remains controversial. We conducted a randomized controlled trial of patients undergoing colorectal surgery at the CHU de Québec-Université Laval. Patients were randomized to regional QL2 anesthesia with 150mg of ropivacaine combined with standard analgesia or to QL2 with a sham intervention and standard analgesia. Our primary outcome was postoperative opioid administration at 24h. Secondary outcomes included opioid administration in the post-anesthesia care unit (PACU), at 48h and at hospital discharge, postoperative pain scores, delay in resumption of intestinal transit, nausea and vomiting, and hospital length of stay. A total of 62 patients were enrolled from November 2017 to February 2018. QL2 regional anesthesia compared with a sham intervention was not associated with a reduction in postoperative morphine dose equivalent (100.2mg, 95% CI 68.9-131.5 versus 88.7mg, 95% CI 59.3-118.0, p = 0.81, respectively). Compared to QL2 regional anesthesia, postoperative pain scores in the control group were lower although statistical significance was not consistent for all postoperative time points. Other secondary outcomes were comparable between both groups. We did not observe a reduction in postoperative opioid administration at 24h with a posterior quadratus lumborum block regional anesthesia in patients undergoing elective colorectal surgery.

Perioperative duloxetine for acute postoperative analgesia: a meta-analysis of randomized trials

BackgroundMultimodal analgesia is a fundamental part of modern surgery and enhanced recovery pathways. Duloxetine, a serotonin and norepinephrine reuptake inhibitor, has been validated for the treatment of chronic neuropathic pain....

Development of a postoperative ileus risk assessment scale: identification of intraoperative opioid exposure as a significant predictor after spinal surgery.

Postoperative ileus (POI) is associated with abdominal pain, nausea, vomiting, and delayed mobilization that in turn lead to diminished patient satisfaction, increased hospital length of stay (LOS), and increased healthcare costs. In this study, the authors developed a risk assessment scale to predict the likelihood of developing POI following spinal surgery. The authors undertook a retrospective review of a prospectively maintained registry of consecutive patients who underwent arthrodesis/fusion surgeries between May 2013 and December 2017. They extracted clinical information, including cumulative intraoperative and postoperative opioid doses using standardized converted morphine milligram equivalent (MME) values. Univariate and multivariate analyses were performed and several categorical and continuous variables were evaluated in a binary logistic regression model built with backward elimination to assess for independent predictors. A points-based prediction model was developed and validated to determine the risk of POI. A total of 334 patients who underwent spinal fusion surgeries were included. Fifty-six patients (16.8%) developed POI, more frequently in those who underwent long-segment surgeries compared to short-segment surgeries (33.3% vs 10.4%; p < 0.001). POI was associated with an increased LOS when compared with patients who did not develop POI (8.0 ± 4.5 days vs 4.4 ± 2.4 days; p < 0.01). The incidences of liver disease (16% vs 3.7%; p = 0.01) and substance abuse history (12.0% vs 3.2%; p = 0.04) were higher in POI patients than non-POI patients undergoing short-segment surgeries. While the incidences of preoperative opioid intake (p = 0.23) and cumulative 24-hour (87.7 MME vs 73.2 MME; p = 0.08) and 72-hour (225.6 MME vs 221.4 MME; p = 0.87) postoperative opioid administration were not different, remifentanil (3059.3 µg vs 1821.5 µg; p < 0.01) and overall intraoperative opioid (326.7 MME vs 201.7 MME; p < 0.01) dosing were increased in the POI group. The authors derived a multivariate model based on the 5 most significant factors predictive of POI (number of surgical levels, intraoperative MME, liver disease, age, and history of substance abuse) and calculated relative POI risks using a derived 32-point system. Intraoperative opioid administration, incorporated in a comprehensive risk assessment scale, represents an early and potentially modifiable predictor of POI. These data indicate that potential preventive strategies, implemented as part of enhanced recovery after surgery protocols, could be instituted in the preoperative phase of care to reduce POI incidence.

Impact of intra-operative dexamethasone after scheduled cesarean delivery: a retrospective study

BackgroundDexamethasone is an effective analgesic and anti-emetic in patients undergoing many surgical procedures but its effects on pain after cesarean delivery are poorly studied. The aim of this study was to evaluate if routine intra-operative administration of dexamethasone improved analgesia and decreased postoperative nausea and vomiting after scheduled cesarean delivery. MethodsElectronic medical record data for scheduled cesarean deliveries performed under neuraxial anesthesia, before and after a practice change that introduced the routine use of intravenous dexamethasone 4 mg, were obtained. Patients were analyzed based on whether they received routine care (n=182) or also received dexamethasone (n=187). The primary outcome was time to first opioid use. Secondary outcomes included postoperative opioid consumption, pain scores, incidence and treatment of postoperative nausea and vomiting, satisfaction and length of stay. ResultsThere was no significant difference between groups in median time to first postoperative opioid administration (15.8 [3.4–48.0] h routine care vs 14.7 [3.2–38.8] h routine care plus dexamethasone, P=0.08). There were no significant differences in any secondary outcomes. ConclusionsThis impact study involving more than 360 patients suggests that routine administration of intra-operative intravenous dexamethasone 4 mg does not provide additional analgesic benefit after scheduled cesarean delivery, in the context of a multimodal postoperative analgesic regimen. Studies are required to determine if a larger dose or repeated administration influence postoperative analgesia or side effects, or whether certain subsets of patients may benefit.

Is 'anxiety sensitivity' predictive of postoperative nausea and vomiting?: A prospective observational study.

Postoperative nausea and vomiting (PONV) is an extremely distressing side effect for patients. Despite PONV prophylaxis guided by well established scoring systems, the incidence of PONV is still high. The aim of the current study was to investigate the predictive value of anxiety sensitivity as an additional independent risk factor for PONV in patients with an increased risk of PONV. A noninterventional, observational study. A tertiary care university hospital. Patients with an increased risk of PONV (i.e. female, nonsmoking) undergoing elective surgery (general, gynaecological, urological, musculoskeletal or neurosurgical) under general anaesthesia. The number of patients with anxiety sensitivity assessed pre-operatively with the Anxiety Sensitivity Index-3 questionnaire, the number of patients experiencing PONV, predictive value of anxiety sensitivity compared with other established risk factors for PONV. Some 41.5% of the patients experienced PONV within the first 24 h after surgery. In these patients increased anxiety sensitivity (Anxiety Sensitivity Index-3 score higher than seven points) was associated with a five-fold increase in the odds ratio (OR) for PONV. From the regression model, the risk of PONV was increased by lack of PONV prophylaxis (OR, 3.68), the postoperative administration of opioids (OR, 3.60) and patient age (OR, 1.03), but laparoscopic surgery did not increase the risk. In addition to the well established risk factors, anxiety sensitivity can help to predict the risk of PONV. It seems justifiable to add psychological factors such as anxiety sensitivity to PONV risk-scores. PONV prophylaxis should be considered when anxiety sensitivity is high. ClinicalTrials.gov identifier: NCT01875120.

Postoperative desaturation and bradypnea after general anesthesia in non-ICU patients: a retrospective evaluation.

Respiratory depression, presenting as desaturation and bradypnea, is common during the early postoperative period. However, it has not been evaluated by appropriate monitoring. The purpose of the present study was to identify the incidence and predictors of desaturation and bradypnea following general anesthesia, using a continuous and centralized monitoring system, in non-ICU patients who did not have serious complications and did not undergo major surgery. Patients were connected to a continuous and centralized monitoring system via a pulse oximeter and respiratory rate sensor for at least 8h after extubation. We assessed the incidence and risk factors for desaturation (SpO2 < 90% for > 10s) and bradypnea (respiratory rate < 8 breaths/min for > 2min) events. We retrospectively collected the clinical data of 1064 adult patients in the study. The incidences of desaturation and bradypnea were 12.1% and 5.1%, respectively. Most desaturation events occurred after the termination of oxygen administration. The greatest incidence of bradypnea was within the first hour after surgery, reducing over time. Analysis revealed that age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.03-1.06; p < 0.001), BMI (OR 1.12, 95% CI 1.06-1.18; p < 0.001) and current smoking (OR 1.91, 95% CI 1.12-3.42; p = 0.023) were significant risk factors for desaturation. Sleep apnea syndrome (OR 4.23, 95% CI 1.09-13.5; p = 0.021) and postoperative opioid administration (OR 2.76, 95% CI 1.44-5.20; p = 0.002) were significantly associated with bradypnea. Age (OR 1.04, 95% CI 1.01-1.07; p = 0.010) and postoperative opioid administration (OR 3.16, 95% CI 1.22-7.87; p = 0.019) showed a significant association with the occurrence of both desaturation and bradypnea. This study demonstrated the incidence and predictors of postoperative desaturation and bradypnea, and suggests the need for monitoring oxygen saturation and respiratory rate for at least 8h after surgery in non-ICU patients. Use of monitoring systems might provide a safety net for postoperative patients.

Morphine Exacerbates Postfracture Nociceptive Sensitization, Functional Impairment, and Microglial Activation in Mice.

Emerging evidence suggests that opioid use immediately after surgery and trauma may worsen outcomes. In these studies, the authors aimed to determine whether morphine administered for a clinically relevant time period (7 days) in a tibia fracture orthopedic surgery model had adverse effects on postoperative recovery. Mice were given morphine twice daily for 7 days after unilateral tibial fracture and intramedullary pin fixation to model orthopedic surgery and limb trauma. Mechanical allodynia, limb-specific weight bearing, gait changes, memory, and anxiety were measured after injury. In addition, spinal cord gene expression changes as well as glial activation were measured. Finally, the authors assessed the effects of a selective Toll-like receptor 4 antagonist, TAK-242, on nociceptive and functional changes after injury. Tibial fracture caused several weeks of mechanical nociceptive sensitization (F(1, 216) = 573.38, P < 0.001, fracture + vehicle vs. sham + vehicle, n = 10 per group), and this change was exacerbated by the perioperative administration of morphine (F(1, 216) = 71.61, P < 0.001, fracture + morphine vs. fracture + vehicle, n = 10 per group). In additional testing, injured limb weight bearing, gait, and object location memory were worse in morphine-treated fracture mice than in untreated fracture mice. Postfracture expression levels of several genes previously associated with opioid-induced hyperalgesia, including brain-derived neurotrophic factor and prodynorphin, were unchanged, but neuroinflammation involving Toll-like receptor 4 receptor-expressing microglia was observed (6.8 ± 1.5 [mean ± SD] cells per high-power field for fracture + vehicle vs. 12 ± 2.8 fracture + morphine, P < 0.001, n = 8 per /group). Treatment with a Toll-like receptor 4 antagonist TAK242 improved nociceptive sensitization for about 2 weeks in morphine-treated fracture mice (F(1, 198) = 73.36, P < 0.001, fracture + morphine + TAK242 vs. fracture + morphine, n = 10 per group). Morphine treatment beginning at the time of injury impairs nociceptive recovery and other outcomes. Measures preventing glial activation through Toll-like receptor 4 signaling may reduce the adverse consequences of postoperative opioid administration.

The Burden of Opioid-Related Adverse Drug Events on Hospitalized Previously Opioid-Free Surgical Patients.

Opioid analgesics are a mainstay for acute pain management, but postoperative opioid administration has risks. We examined the prevalence, risk factors, and consequences of opioid-related adverse drug events (ORADEs) in a previously opioid-free surgical population. A retrospective, observational, cohort study using administrative, billing, clinical, and medication administration data from two hospitals. Data were collected for all adult patients who were opioid-free at admission, underwent surgery between October 1, 2015, and September 30, 2016, and received postoperative opioids. Potential ORADEs were determined based on inpatient billing codes or postoperative administration of naloxone. We determined independent predictors of ORADE development using multivariable logistic regression. We measured adjusted inpatient mortality, hospital costs, length of hospital stay, discharge destination, and readmission within 30 days for patients with and without ORADEs. Among 13,389 hospitalizations where opioid-free patients had a single qualifying surgery, 12,218 (91%) received postoperative opioids and comprised the study cohort. Of these, we identified 1111 (9.1%) with a potential ORADE. Independent predictors of ORADEs included older age, several markers of disease severity, longer surgeries, and concurrent benzodiazepine use. Opioid-related adverse drug events were strongly associated with the route and duration of opioids administered postoperatively: 18% increased odds per day on intravenous opioids. In analyses adjusted for several covariates, presence of an ORADE was associated with 32% higher costs of hospitalization, 45% longer postoperative length of stay, 36% lower odds of discharge home, and 2.2 times the odds of death. We demonstrate a high rate and severe consequences of potential ORADEs in previously opioid-free patients receiving postoperative opioids. Knowledge of risk factors and predictors of ORADEs can help develop targeted interventions to minimize the development of these potentially dangerous and costly events.

Intraoperative Dexamethasone Decreases Infectious Complications After Pancreaticoduodenectomy and is Associated with Long-Term Survival in Pancreatic Cancer

Dexamethasone is administered intraoperatively to prevent anesthesia-related nausea and vomiting and to reduce postoperative opioid administration. However, the adverse effects of corticosteroids on anastomotic healing and wound infection as well as oncologic outcomes remain unclear. We analyzed the effect of intraoperative dexamethasone administration on surgical outcomes after pancreaticoduodenectomy and on long-term survival in pancreatic cancer patients. A total of 679 pancreaticoduodenectomies from a prospectively maintained database were analyzed. Surgical outcomes were compared between patients who received intraoperative dexamethasone and those who did not. Kaplan-Meier curves and Cox-regression survival analysis were performed in patients with pancreatic cancer. A propensity analysis was done to reduce the inherent bias of retrospective design. Patients who received dexamethasone (117, 17.2%) were younger and more likely to be female than those who did not (p = 0.001). Overall and 30-day major morbidity were similar among all resected patients, although there were fewer infectious complications in the dexamethasone group (18.8% vs. 28.5%, p = 0.032). In pancreatic cancer patients, dexamethasone was associated with significantly improved median overall survival (46 vs. 22months, p = 0.017). This effect occurred independently of stage, pathologic characteristics, or adjuvant therapy, with adjusted hazard ratios, derived from pre-propensity and post-propensity analysis, of 0.67 (0.47-0.97) and 0.57 (0.37-0.87), respectively. A single intraoperative dose of dexamethasone did not increase morbidity after pancreaticoduodenectomy and, in fact, was associated with a decrease in infectious complications. The treatment was independently associated with improved overall survival in patients with pancreatic adenocarcinoma, an effect that cannot be explained and needs further validation in a prospective setting.

Paravertebral block associated with decreased opioid use and less nausea and vomiting after reduction mammaplasty

BackgroundIn light of data finding that postoperative pain, nausea, and vomiting worsen outcomes, a renewed emphasis has been placed on optimizing the perioperative period. Use of preoperative paravertebral block (PVB) has been shown to reduce opioid administration and postoperative nausea and vomiting (PONV) in many surgical populations, though its role in reduction mammaplasty remains undefined. Therefore, we seek to evaluate PVB as an adjunct to general anesthesia (GA) for reduction mammaplasty. Materials and methodsWe reviewed records for patients who underwent reduction mammaplasty at our institution from 2010 to 2015. Patients were categorized into two groups: GA alone and GA + PVB (GA with PVB adjunct). Demographic information, opioid administration, phase I/II pain scores, presence of PONV, and anesthesia time were analyzed. Analysis was performed using t-tests and Fisher's exact test, with P-values less than 0.05 statistically significant. ResultsWe identified 264 patients meeting criteria: 209 (79%) received GA alone and 55 (21%) received GA + PVB. Intraoperative opioid administration were lower for GA + PVB patients (morphine equivalent of 44 mg versus 35 mg, P = 0.019), though there was no difference in postoperative opioid administration (P = 0.915). Phase I and II pain scores were significantly lower for those receiving PVB (2.9 versus 3.9, P = 0.012, and 3.0 versus 4.2, P = 0.001, respectively). GA + PVB was associated with less PONV (14% versus 33%, P = 0.007) and longer anesthesia times (271 min versus 236 min; P = 0.001). ConclusionsBy improving pain control and reducing PONV, factors known to be associated with poor patient satisfaction and inferior outcomes, PVB is an attractive anesthetic adjunct in elective breast surgery.

The use of dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium in cardiac surgery patients over 60 years of age: a pilot study

Background: Delirium is associated with many negative health outcomes. Postoperative sedation and opioid administration may contribute to delirium. We hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA) may lead to reduced opioid consumption and decreased incidence of postoperative delirium. This pilot study aims to assess feasibility of using dexmedetomidine and IVA in cardiac surgical patients, and estimate the effect size for incidence and duration of delirium. Methods: A total of 12 adult patients &gt;60 years of age undergoing cardiac surgery were recruited and randomized into 4 groups: Propofol only (P), Propofol with IVA (P+A), Dexmedetomidine only (D), Dexmedetomidine with IVA (D+A). Preoperative baseline cognition and postoperative delirium was assessed daily until discharge. The feasibility was assessed by the number of patients who completed the study. Results: All patients completed the study successfully. The total incidence of delirium in the study population was 42% (5/12): 67% (2/3) in the group P, and 67% (2/3) in the group D, 33% (1/3) in D+A group and 0%(0/3) P+A group. The incidence of delirium was 17% (1/6) in the group receiving IVA compared to 67% (4/6) that did not receive IVA. The mean range of duration of delirium was 0-1 days. One patient expired after surgery, unrelated to the study protocol. One patient in the D group experienced hypotension (systolic blood pressure &lt;90 mm of Hg.) Conclusions: The feasibility of performing a project is ascertained by the study. Patients receiving IVA had lower incidence of delirium compared to patients not receiving IVA which suggests that IVA may have a role in reducing the incidence of delirium. A prospective randomized, placebo-controlled trial will be the next step in investigating the role of dexmedetomidine and IVA in reducing the incidence of delirium.

The use of dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium in cardiac surgery patients over 60 years of age: a pilot study

Background: Delirium is associated with many negative health outcomes. Postoperative sedation and opioid administration may contribute to delirium. We hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA) may lead to reduced opioid consumption and decreased incidence of postoperative delirium. This pilot study aims to assess feasibility of using dexmedetomidine and IVA in cardiac surgical patients, and estimate the effect size for incidence and duration of delirium. Methods: A total of 12 adult patients >60 years of age undergoing cardiac surgery were recruited and randomized into 4 groups: Propofol only (P), Propofol with IVA (P+A), Dexmedetomidine only (D), Dexmedetomidine with IVA (D+A). Preoperative baseline cognition and postoperative delirium was assessed daily until discharge. The feasibility was assessed by the number of patients who completed the study. Results: All patients completed the study successfully. The total incidence of delirium in the study population was 42% (5/12): 67% (2/3) in the group P, and 67% (2/3) in the group D, 33% (1/3) in D+A group and 0%(0/3) P+A group. The incidence of delirium was 17% (1/6) in the group receiving IVA compared to 67% (4/6) that did not receive IVA. The mean range of duration of delirium was 0-1 days. One patient expired after surgery, unrelated to the study protocol. One patient in the D group experienced hypotension (systolic blood pressure <90 mm of Hg.) Conclusions: The feasibility of performing a project is ascertained by the study. Patients receiving IVA had lower incidence of delirium compared to patients not receiving IVA which suggests that IVA may have a role in reducing the incidence of delirium. A prospective randomized, placebo-controlled trial will be the next step in investigating the role of dexmedetomidine and IVA in reducing the incidence of delirium.