Despite the high frequency of nerve blocks in the acute phase of herpes zoster, factors associated with intervention, such as response to epidural block, have not been analyzed as predictive factors of postherpetic neuralgia (PHN). To determine the predictive factors of progression to PHN in the presence of interventions, we analyzed the medical records of 145 patients who underwent transforaminal epidural injection (TFEI) in the acute phase of herpes zoster. A total volume of 5 mL (a mixture of 0.5% lidocaine and 5 mg dexamethasone) was injected during TFEI. Corticosteroid was used only for the first TFEI. Clinical data of age, sex, involved dermatome, presence of comorbidity, time from zoster onset to first TFEI, numerical rating scale (NRS) before TFEI, NRS at 1 week and 1, 3, and 6 months after the first TFEI, and number of TFEI were collected and analyzed. Through multivariate logistic regression analysis, pain improvement less than 50% at 1 week after the first TFEI was a strong predictive factor of progression of PHN at all time points. Response to TFEI appears to be a stronger predictive factor of progression to PHN than patient factors of sex, age, degree of initial pain, and presence of co-morbidity. Herpes zoster is a disease caused by reactivation of dormant varicella zoster virus (VZV). VZV latent in the dorsal root ganglion (DRG) is replicated and spread along the nerve, causing pain and skin lesion following the corresponding dermatome . The acuPHN is the most common complication of herpes zoster and has a reported incidence of 10 to 34%, depending on definition ,6,7. PHNVarious clinical features, including age over 50 years, presence of comorbidity, severe pain, and extensive skin lesion, are known predictive factors of PHN ,7,8,9,10Although nerve blocks are often applied during the acute phase of herpes zoster, factors associated with intervention, such as response to epidural block, have not been analyzed as predictive factors of PHN.The aim of this study was to determine the predictive factors of progression to PHN in the presence of interventional factors. For this purpose, we analyzed the medical records of patients who underwent TFEI in the acute phase of herpes zoster.Permission to conduct this study was obtained from the Institutional Ethics Committee of Daejeon St. Mary’s Hospital, Republic of Korea (DC19OESI0006). The medical records of patients who underwent TFEI within one month of zoster onset to control ZAP at Daejeon St. Mary’s Hospital Pain Center from April 2014 and June 2018 were collected. TFEI was performed on zoster patients with zoster involving the lumbosacral to thoracic dermatome and who complained of moderate to severe ZAP. Cases of zoster involving the cervical dermatome, facial zoster, infection at the site of injection, coagulopathy, and pregnancy were not indicated for TFEI.All patients were prescribed analgesics, such as aceclofenac and tramadol/acetaminophen combination tablets. When neuropathic features of electric shock-like pain or allodynia were observed, pregabalin and nortriptyline were used as an anticonvulsant and tricyclic antidepressant, respectively. All participants received appropriate antiviral treatment. The medical records of patients who did not receive appropriate antiviral agents within 72 hours after skin rash were excluded from the study. Medical records from patients who had received the first TFEI beyond one month of zoster onset were also excluded from this analysis. Patients were placed in a prone position on a fluoroscopic-compatible table. The needle entry site was prepared and draped in a sterile fashion. A fluoroscope was placed obliquely toward the ipsilateral side. After local infiltration, a 22-G Quincke needle was introduced inferior to the pars interarticularis under fluoroscopic guidance at the level of pathology.The needle tip position was adjusted to inferior to the pedicle in the anteroposterior view. To minimize the possibility of vascular injury, the needle tip was positioned in the lower posterior portion of the intervertebral foramen in the lateral view of the fluoroscopic image .A total of 2 to 3 mL of contrast agent  was used to confirm needle tip position. Then, 5 mL of a mixture of 0.5% lidocaine and 5 mg dexamethasone was injected. Corticosteroid was added to the injectate only for the first administration of TFEI. All TFEI procedures were conducted by a physician experienced in pain management (E.D.K.).The following data were collected from medical records and analyzed: age, sex, involved dermatome, presence of comorbidity, time from zoster onset to first TFEI, numerical rating scale (NRS) before TFEI, NRS at 1 week and 1, 3, and 6 months after TFEI, and number of TFEI procedures performed during the review period.PHN was defined as the presence of pain with an NRS score of 1 or higher. The examination time points were set at 1 month, 3 months, and 6 months after the first TFEI. The presence of PHN and variables of interest at these time points were evaluated. Pain intensity prior to TFEI (baseline pain) was classified as moderate pain between NRS 3 and 6 and severe pain from NRS 7 to 10. Characteristics of baseline pain were classified according to the presence of neuropathic features.Age was classified as 50 years or older and less than 50 years. Comorbidity was categorized as cardiovascular, diabetes, two or more diseases combined, and no underlying disease.The time of TFEI was classified as having received the first TFEI within 15 days after zoster onset or between 16 and 30 days after zoster onset. We asked patients to revisit our pain center one week after TFEI for ZAP assessment using the NRS. The response to TFEI was divided into cases of pain improvement of 50% or more (remaining pain ≤ 50% of baseline NRS) or pain improvement less than 50% (remaining pain > 50% of baseline NRS) when evaluated at 1 week after the first TFEI. If the intensity of the worst pain over the last 24 h was greater than NRS 3, we recommended repetition of TFEI. The number of TFEI performances was categorized as once or more than once. t-test for continuous variables and Chi-square or Fisher’s exact test for categorical variables. A p-value less than 0.05 was considered statistically significant.Demographic data of the patients were analyzed using Student’s To determine independent risk factors associated with development of PHN among the clinical data and demographic characteristics of the participants, binary logistic regression techniques were used.r > 0.7) and were further selected with a forward stepwise procedure . All data were analyzed using SPSS version 18.0 . All parametric data are presented as the mean ± standard deviation (SD) and nonparametric data as number and proportion. Odds ratio (OR) with 95% confidence interval (CI) was also calculated as needed.Variables were screened by examining for multicollinearity  than men (n = 41). The mean baseline NRS prior to the first TFEI was 6.41 ± 1.27, and the mean time of receiving the first TFEI after zoster onset was 10.47 ± 6.84 days.The mean age of the patients was 61.95 ± 13.47 years. There were many more women  had no underlying disease. Neuropathic pain features were observed in almost all patients (97.9%). p < 0.0001, 3 months: 9/14, 64.3% vs. 28/131, 21.4%; p = 0.008, 6 months: 6/10, 60.0% vs. 31/135, 22.9%; p = 0.010).The PHN ratio was 36.5% at 1 month, 9.6% at 3 months, and 6.8% at 6 months after the procedure. At all of the time points, the proportion of cases with pain improvement less than 50% at 1 week after the first TFEI was significantly higher in PHN patients than non-PHN patients  and the ratio of severe baseline pain intensity  were significantly higher in PHN patients than non-PHN patients. At 6 months, the proportion of patients who received the first TFEI beyond 15 days of zoster onset was significantly higher in the PHN patients than non-PHN patients   .p = 0.010) and severe baseline pain  were significant predictive factors of PHN at 1 month. Performance of the first TFEI beyond 15 days after zoster onset was a significant predictive factor of PHN at 6 months . At all of the time points, pain improvement less than 50% at 1 week after the first TFEI was a strong predictive factor of progression of PHN .The results of multivariate logistic regression are described in In the present study, less than 50% improvement at 1 week after the first TFEI was a strong predictive factor of progression of PHN at all time points. The time to first TFEI after zoster was an additional significant PHN predictive factor at 6 months. Previous studies have reported age over 50 years, female gender, comorbidity, extensive skin lesion, and severe pain in the acute phase as predictive factors of PHN progression ,7,8,9,10Epidural block has been commonly used to control ZAP in the acute phase and prevent progression to PHN; however, there is still controversy about its efficacy to prevent PHN ,13,14,15Considering that VZV is reactivated in the DRG, this would be an appropriate target lesion for intervention at the time of acute zoster ,17,18. TIn this study, patient factors such as baseline pain intensity and age of 50 years or older were significant predictors of PHN in only the relatively early period, such as 1 month after the procedure. However, such patient factors were no longer significant when predicting PHN at 3 months after the procedure. In contrast, at all of the time points, regardless of age, comorbidity, severity of baseline pain, and initial neuropathic features, the response to TFEI was a strong factor to predict progression to PHN. This suggests that suppression of the nociceptive signal in neuronal tissues, such as the DRG, is very important in inhibiting progression to PHN. Perhaps the degree of blockage of nociceptive signal might be more influential on progression to PHN than patient factors such as age, sex, intensity of initial pain, and presence of comorbidity. One of the limitations of present study was that it was unable to strictly control factors such as dose of analgesics or anticonvulsant due to its retrospective nature. Another limitation is that the analysis was based on a relatively small sample size collected from a single hospital. However, this study was the first to investigate the predictive factors of progression to PHN, including the presence of intervention, such as TFEI, and more likely to be performed in close proximity to the actual clinical situation.In conclusion, the response to TFEI in the acute phase of herpes zoster appears to be a strong predictive factor of progression to PHN. We believe that if no meaningful effect is observed during follow-up of patients after TFEI, another type of intervention, such as continuous epidural block or pulsed radiofrequency, should be considered so as not to delay suppression of nociceptive signaling to the central nervous system. Based on our findings, further prospective studies are needed to develop a more appropriate treatment protocol for ZAP control and prevention of PHN.


BackgroundSupartz FX  has been investigated as a therapeutic for knee osteoarthritis (OA) due to its claimed preservation of viscoelastic joint properties and improvement in pain and physical function. The US prescribing information suggests patients may experience benefit with as few as three of five injections administered once weekly. However, recommended guidelines from the American Academy of Orthopaedic Surgeons (AAOS) do not support injectable hyaluronate due to controversial results of randomized controlled trials.ObjectiveDo patients experience statistically and/or clinically significant improvement in disability scores following three injections?MethodsA total of 32 patients with a mean age of 66±14 years receiving Supartz FX were reviewed in a prospective, observational study. Functional outcome data via Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical function were collected at 0, 1, 2 and 3 weeks, and means were analyzed via paired t-test.ResultsThree injections at one-week intervals resulted in statistically significant improvement across all sub scores (p<0.05). Confidence intervals (CIs) of treatment effects  for pain , stiffness , and function  were recorded and compared to published minimum clinically important improvement (MCII) thresholds.ConclusionDespite manufacturer recommendations, in this study short-term use of Supartz FX for knee OA does not meet clinically significant thresholds as the treatment effects for WOMAC sub scores fail to satisfy published MCII for pain (0.39), stiffness (0.39) and function (0.37). In light of these findings and in concordance with recommendations set forth by the AAOS, this study contributes to a preventative medicine database that encourages exploration of non-surgical and non-opiate modalities for the management of osteoarthritis. Osteoarthritis (OA) is the most common joint disorder in the United States, affecting approximately 27 million Americans . OA mostLess severe forms of knee OA are commonly managed with intra-articular HA (IAHA) injections, though meta-analyses of randomized controlled trials have failed to identify significant clinical changes in outcomes between IAHA and placebo . Balazs Previous studies have explored the efficacy of high-molecular-weight HA models using Likert-type Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain and physical function -8. AdditStudy subjectsFifty-five patients  were screened to participate in this study. The inclusion criteria were unilateral knee OA (Kellgren-Lawrence Grade 2 or 3) confirmed by radiographs. The exclusion criteria were bilateral knee OA, previous IAHA, viscosupplementation, or corticosteroid injection into the knee less than three months from starting Supartz FX; concomitant knee disease, ligamentous instability on physical exam, and ongoing anticoagulant therapy.Study designAs a consecutive case-series, patient-reported outcomes following Supartz FX were recorded using WOMAC scores before and one-week after each of three injections. WOMAC scores are based on five items related to pain , 2 items related to stiffness , and 17 items related to physical activity . The summed score is normalized to a total out of 100.Statistical analysisWOMAC sub score data, computed to a normalized value of 100, and mean percent reductions, were recorded at weeks 0, 1, 2 and 3. Sub scores were analyzed using a paired 2-sample t-test. A value of p<0.05 was considered statistically significant and data are represented as the mean ± standard error (SE) of the mean. Weekly sub score changes were statistically analyzed for effect size at a 95% confidence interval and compared to published minimum clinically important improvement (MCII) thresholds.Thirty-two patients  aged between 35-89  met the inclusion criteria. The average weight was 95.3±27.1 kg, and the average height was 1.67±0.11 m. The average body mass index (BMI) as 34.2±7.9 kg/m2. 23 patients were obese (BMI ≥ 30.00 kg/m2), seven were overweight (BMI 25.00-29.99 kg/m2), and two patients were considered normal weight (BMI 18.5-24.99 kg/m2). Percent mean improvement (%) in WOMAC sub scores were recorded weekly , stiffness (5.3±1.3), and physical function (35.1±9.6) to "Injection 1" sub scores for pain (9.7±2.5), stiffness (4.2±1.5), and physical function (29.2±7.6) were recorded. These and the subsequent values listed below are represented by each of the consecutive data bars in Figure 1.5±2.7, A decrease from "Injection 1" sub scores for pain (9.7±2.5), stiffness (4.2±1.5), and physical function (29.2±7.6) to "Injection 2" sub scores for pain (6.4±2.5), stiffness (3.0±1.3), and physical function (22.0±7.2) were recorded.A decrease from "Injection 2" sub scores for pain (6.4±2.5), stiffness (3.0±1.3), and physical function (22.0±7.2) to "Injection 3" sub scores for pain (4.8±2.0), stiffness (2.2±1.1), and physical function (16.7±5.4) were recorded.Scores for the obese cohort (BMI ≥ 30.00 kg/m2) were analyzed by comparing baseline values of physical function only to those after the third injection. Neither mean percent improvement nor statistical significance were used to evaluate these specific changes within the obese group  occurs after just two injections, evidenced by the highest percent reduction in WOMAC scores occurs following the second injection (p<0.05) Figure . The perStatistical significance in and of itself provides data regarding sample size but does not incorporate the procedure’s clinical significance to patients. Therefore, interpretation of results using MCII thresholds corroborates statistical significance by highlighting the smallest clinical change important to patients. Study results are considered clinically significant if the lower confidence interval of its treatment effect size is greater than the MCII, and not clinically significant if its upper confidence interval lies below or includes the MCII.Variation may exist within different patient populations, causing discrepancies in what one patient considers clinically significant compared to another, either from subjective experience or baseline disease. However, the MCII serves as a reasonable proxy for evaluating meaningful improvement within populations of similar demographics. Thus, the MCIIs used here are derived from previously published data. In Guidelines for Treatment of Osteoarthritis of the Knee, the American Academy of Orthopaedic Surgeons (AAOS) used effect sizes reported by Angst et al. to compute thresholds for WOMAC sub scores of pain (0.39), function (0.37), stiffness (0.39), cumulative (0.40) .Weekly mean sub score data shown in Figure These results contribute to a discourse on osteoarthritis from an evidence-based medicine (EBM) perspective. EBM often incorporates the best evidence, clinical expertise, and patient wishes when making an informed decision. Therefore, while the evidence for use of IAHA is inconclusive (and not recommended by the AAOS), clinicians should exercise clinical judgment and accommodate patient preference when explaining the benefits and harms of IAHA. Certain groups of patients may respond better to intra-articular Supartz FX than others. For example, Figure The use of intra-articular hyaluronic acid injections has been well studied, though evidence of improvement in pain, stiffness, and disability versus placebo has been controversial. Further data supporting its efficacy has been unconvincing, and the AAOS does not recommend the use of IAHA in clinical practice. Despite manufacturer recommendations, short-term use of Supartz FX for knee osteoarthritis does not meet clinically significant thresholds as the treatment effects for WOMAC sub scores fail to satisfy published MCII criteria.


Spousal caregivers of chronic pain patients may experience high levels of negative affect, perhaps in part because they regularly witness patients’ suffering. Yet, few studies have examined the relation between patients’ chronic pain and spousal caregivers’ negative affect. According to social cognitive theory, individuals’ self-efficacy may modulate how much negative affect they experience in response to stressful situations. The purpose of this study was to test the hypothesis that spousal caregivers would report higher levels of negative affect on days when patients experienced higher levels of knee pain. We also tested the hypothesis that patients’ and spouses’ self-efficacy for managing pain would each buffer this positive association. A total of 144 knee osteoarthritis (OA) patients and their spouses completed baseline interviews and a 22-day diary assessment. Multilevel models indicated that patients’ self-efficacy, but not spouses’ self-efficacy, moderated the positive association between patients’ pain and their spouses’ negative affect, even after controlling for spouses’ gender, age, and depressive symptoms. That is, spouses reported higher levels of negative affect on days when patients experienced more pain, but only among patients whose self-efficacy for managing pain was low. These findings suggest that patients’ self-efficacy for managing pain may serve as a protective factor for their spousal caregivers’ daily negative affect. Interventions targeting patients’ self-efficacy for managing pain may be beneficial for couples coping with knee OA.


IntroductionAssessment and management of postoperative pain in the pediatric population after anterior cruciate ligament (ACL) surgery can be challenging; the optimal approach to pain control remains controversial. Recent studies show that use of intraoperative nerve blocks may reduce the need for opioids to control pain in the postoperative period. However, it is unclear which block type is most beneficial in the pediatric outpatient setting. This study compared effectiveness of pain control among three different pain management strategies.MethodsWe retrospectively reviewed charts of patients aged 12-17 years who received an elective ACL reconstruction between 2013 and 2017. The three groups were femoral nerve block, combined femoral and sciatic block, and intraarticular injection of bupivacaine (n = 50 per group). The primary variable was postoperative pain scores  in the postanesthesia care unit (PACU).ResultsLess than 50% of patients in the combined nerve block group had opioids intraoperatively or in the PACU compared with nearly 100% of patients in the other two groups (p < 0.0001). Also, for patients receiving opioids, the total intraoperative morphine equivalents and PACU pain scores  were significantly less in the combined block group (p < 0.001). For patients receiving opioids in the PACU, the total morphine equivalents were significantly higher in the intraarticular injection group compared with the nerve block groups (p < 0.0001).ConclusionPatients in the combined femoral and sciatic nerve block group had significantly better pain scores in the PACU with less cumulative morphine equivalent consumption compared with the femoral nerve block group and the intraarticular injection group. Increased use of regional anesthesia in infants, children, and adolescents has significantly improved the scope of pediatric pain management. Performance of regional anesthesia can be safely and effectively applied to pediatric patients, and these techniques are becoming increasingly popular -3. As a Prior to availability of ultrasound imaging for regional anesthesia, many providers were reluctant to perform peripheral nerve blockade (PNB) in the pediatric population. Regional techniques utilizing landmarks or nerve-stimulation methods were typically avoided in children due to the difficulty in targeting neural structures that are often in close proximity to other critical structures . These pFollowing the introduction of ultrasound-guided nerve localization, regional anesthetic techniques gained popularity as a method to improve pain management among children undergoing orthopedic procedures. A study using large prospective databases has demonstrated the ability to safely perform regional anesthesia in children with minimal risk of neurological damage using sedation or general anesthesia . In addiAdvanced pain management techniques are associated with a unique set of risks and benefits. For example, although a femoral and sciatic nerve block would provide complete postoperative analgesia after a knee arthroscopy for anterior cruciate ligament (ACL) repair, these techniques may be associated with perioperative nerve injury, prolonged dysesthesias, motor weakness, or bleeding and infectious complications . In contClinical trials comparing these analgesic modalities with one another are lacking, resulting in a significant knowledge gap and inability to determine which pain management technique is best suited for patients undergoing knee arthroscopy and ACL repair. Therefore, the primary goal of our study was to compare pain control and opioid usage between a combination of PNBs  versus intraarticular injections of bupivacaine-based local anesthetic.We hypothesized that pediatric patients undergoing knee arthroscopy for ACL repair will have lower postoperative pain, lower consumption of opioid medications, and faster recovery and hospital discharge with PNB compared with intraarticular injections using bupivacaine in the immediate postoperative period. We also hypothesized that there would be no significant difference in the immediate postoperative outcome between use of a femoral nerve block with the combined femoral and sciatic nerve block combination.We performed a multisite retrospective chart review consisting of patients with American Society of Anesthesiology (ASA) I and II with three different pain management strategies during an elective unilateral ACL reconstruction  between 2013 and 2017. This study was approved by our Institutional Review Board. Patients aged 12 to 17 years who had elective ACL reconstruction were included in this study. There were 50 patients consecutively chosen from the search list per group. The power analysis was based on the differences between femoral nerve block plus sciatic nerve block vs. intraarticular injection, as the literature suggests these may be the groups with the best and worst pain scores . A difference of 2 on the pain scale is believed to be clinically significant. Postanesthesia care unit (PACU) pain scores have not been tabulated in previous studies, so we have no historical data to use to estimate the degree of variability . To detect a 2-point difference at 90% power, assuming SD equals 2, alpha equals 0.05 (two-tailed), we would need about 25 patients per group. But if we see that the SD is closer to 3 after the first 10 patients, then about 50 patients per group will be required. The primary variable collected was postoperative pain score  every 15 minutes until the patient was discharged home. The pain scores were recorded in the PACU by a single nurse on a one-to-one care basis after the patient awoke from general anesthesia. This score was plotted on a flowsheet in the electronic medical record . Secondary variables collected were demographic data, time in PACU, and intraoperative/postoperative analgesic use.All patients received the same protocol with intravenous induction with propofol and maintenance of general anesthesia with sevoflurane and laryngeal mask airway placement before the block or intraarticular injection. Blocks were given using ultrasound  before the incision. After aseptic preparation of the puncture site and ultrasound probe, the nerve blocks were performed using an insulated 22-gauge needle with facette tip and injection line . All blocks were performed with the in-plane technique. The needle was positioned close to the target nerves under ultrasound visualization. The local anesthetic ropivacaine  was injected under real-time ultrasound control until the nerve was surrounded. An observer injected the local anesthetic and recorded the injected amount. All patients in the intraarticular injection group received bupivacaine  after surgery was completed. At the end of the surgery, the patient was taken to the recovery room and assessment of pain was done every 15 minutes using the VAS until discharge.Statistical analysesDescriptive statistics (mean ± standard deviation) were calculated. Results for the three groups were compared using the Kruskal-Wallis nonparametric analysis of variance (ANOVA) test  followed by Dunn’s multiple comparisons test (which compared each group with every other). Percentages were compared using the chi-squared test for trend.There was no statistically significant difference in mean age of patients in the three groups: 15.6 ± 1.3, 15.1 ± 1.4, and 15.1 ± 1.4 years for femoral nerve block patients, combined block, and intraarticular injection, respectively. Likewise, there was no difference in body mass index: 26.7 ± 6.4, 24.8 ± 6.0, and 24.8 ± 5.3. The ratio of boys to girls was similar in the three groups, with boys comprising 54%, 40%, and 46% in femoral nerve block patients, combined block, and intraarticular injection, respectively. However, there was a difference in race profiles among the three groups (a manifestation of site location); for the femoral nerve block group, only 28% were Caucasian, compared with 58% and 56% in the combined block group and intraarticular injection group, respectively (p = 0.002).Table The practice of pediatric regional anesthesia has made tremendous strides in recent years. Advances in ultrasonography and precise dosing regimens have facilitated widespread applications of regional anesthetic techniques in infants, children, and adolescents. Prospective studies indicate that these techniques can be safely performed and positively impact the outcomes of pediatric patients undergoing painful procedures ,9. Safe A fundamental knowledge of the anatomical structure of the knee and associated neural innervation is critical to understand the utility and limitations of specific nerve blocks in managing postsurgical pain. Innervation of the knee comes from nerves arising from the lumbar plexus and the sciatic nerve. Femoral nerve block is an effective and safe method of providing postoperative analgesia to children and adolescents undergoing orthopedic knee surgery . In manyIn our study, the femoral and sciatic nerve block group had statistically significant better pain scores with less cumulative morphine equivalent consumption use compared with the intraarticular injection group and the femoral nerve block group both intraoperatively and in the PACU. However, despite needing less pain medication in the PACU, the double PNB group had a longer stay in recovery. One possible theory explaining this finding is that a combined femoral plus sciatic block is a denser block leaving the patient weaker and insensate longer and thus making it more difficult to meet discharge requirements. That is, the patients with combined blocks likely required more time to perform transfers and learn use of crutches, explaining the longer time in recovery. The ability to provide site-specific analgesia coupled with the ability to reduce opioid requirements produces patients who are comfortable and symptom-free in the recovery room. Moreover, decreasing the time to meet discharge criteria after regional anesthesia likely means that these patients will be more alert during the recovery phase, as decreasing opioid administration diminishes opioid-induced side effects such as drowsiness and somnolence.New techniques in regional anesthesia are emerging frequently. During the last couple of years, adductor canal blocks have been taking over femoral nerve blocks in some practices. By targeting the distal branches of the femoral nerve in the mid-thigh, the adductor canal block can preserve quadriceps muscle strength while providing analgesia similar to a conventional femoral nerve block for patients undergoing major knee surgery. Jaeger et al. showed that an adductor canal block produces a quadriceps strength reduction of 8% compared with 49% after a femoral nerve block .In a randomized, double-blind study, the authors found that adductor canal block provides postoperative analgesia that is noninferior to femoral nerve block in the first 24 hours, while preserving quadriceps strength after outpatient ACL reconstruction .This study revealed that there is better pain control for ACL reconstruction in the immediate postoperative period with a combined femoral plus sciatic nerve block. However, further work is needed to include a larger possibly multicentered prospective randomized study, with a single anesthesiologist providing the blocks, and with surgery done at a single hospital and PACU staff. A study limited to a single anesthesiologist and single surgeon might help to decrease inevitable bias with three different practice patterns. Also, the future prospective studies should evaluate postoperative pain longer than during the PACU stay, a minimum of a week of daily follow-up and evidence of a rebound effect, quadriceps weakness, pain with movement, and with more standard times for pain assessment and treatment. To optimize pain management, adductor canal block (to decrease quadriceps weakness) and usage of a new formulation of local anesthetic, liposomal bupivacaine (now widely available and approved for wound infiltration), might be the future of regional anesthesia for postoperative pain in the pediatric population. Also, new prospective studies are needed with the new implemented federal and state regulations regarding fewer days of opioid prescriptions for acute pain management. Regional anesthesia can potentially help decrease the current opioid epidemic.


Pain is a common and distressing symptom in people with cancer, but is under-recognised and under-treated. Australian guidelines for ‘Cancer Pain Management in Adults’ are available on the Cancer Council Australia Cancer Guideline Wiki. This study aims to evaluate the effectiveness and cost-effectiveness of a suite of guideline implementation strategies for improving pain outcomes in adults with cancer in oncology and palliative care outpatient settings.The study will use a stepped-wedge cluster randomised controlled design, with oncology and palliative care outpatient services as the clusters. Patients will be eligible if they are adults with cancer and pain presenting to participating services during the study period. During an initial control arm, services will routinely screen patients for average and worst pain over the past 24 h using a 0–10 numerical rating scale (NRS) and have unfettered access to online guidelines. During the intervention arm, staff at each service will be encouraged to use: 1) a patient education booklet and self-management resource; 2) an online spaced learning cancer pain education module for clinicians from different disciplines; and 3) audit and feedback of service performance on key indices of cancer pain screening, assessment and management. Service-based clinical change champions will lead implementation of these strategies.N = 492) will provide > 90% power. A qualitative sub-study and analyses of structural and process factors will explore opportunities for further refinement and tailoring of the intervention.The trial’s primary outcome will be the probability that patients initially screened as having moderate-severe (≥5/10 NRS) worst pain experience a clinically important improvement one week later, defined as  ≥ 30% reduction. Secondary outcomes will include patient empowerment and quality of life, carer experience, and cost-effectiveness. For the main analysis, linear mixed models will be used, accounting for clustering and the longitudinal design. Eighty-two patients per service at six services .Registered 23/01/2015 on the Australian New Zealand Clinical Trials Registry ( Despite of decades of research and practice improvement initiatives, 39–66% of people with cancer experience pain, and up to 40% of people with pain receive inadequate analgesia , 2. Undedevelopment phase of our program involved a national survey of current practice [piloting phase tested the feasibility of screening for pain and auditing pain assessment and management in adults attending palliative care and oncology services [evaluation phase, which aims to test the effectiveness and cost-effectiveness of all three guideline implementation strategies combined for improving pain outcomes in adults with cancer attending oncology and palliative care outpatient services.The current authors have undertaken a program of work to develop and implement Australian guidelines for ‘Cancer Pain Management in Adults’, which are now available online via the Cancer Council Australia Cancer Guidelines Wiki , 17. Thipractice –22, two practice , 23 and practice . This prservices . The curThe study’s primary aim is to evaluate capacity for a suite of three guideline implementation strategies to increase the probability that patients initially screened as having moderate-severe (≥5) worst pain on a 0–10 numerical rating scale (NRS) will experience a clinically important improvement of ≥30% one week later.to evaluate capacity of the three guideline implementation strategies versus a control arm to:i.reduce mean worst and average pain severity across all patients screened as having clinically relevant (≥2 NRS) or moderate-severe (≥5 NRS) worst pain from time of screening to one, two and four week later by half a standard deviation (0.5 SD);ii.demonstrate a between-arm difference in patient empowerment in patients screened as having clinically relevant (≥2 NRS) worst pain, as measured by 0.5 SD difference on the Health Education Impact Questionnaire (heiQ) (41) at one, two and four weeks post-screening;iii.demonstrate a between-arm difference in the experiences of unpaid carers of participating patients, as measured by a 0.5 SD difference on the Carer Experience Scale (CES)  at two aiv.demonstrate a between-arm difference on mean patient quality of life (QOL), as measured by a difference of 0.5 SD on the European Organisation for Research and Treatment of Cancer Palliative Care (EORTC QLQ C15-PAL)  at two a2.to evaluate the cost-effectiveness of the three guideline implementation strategies based on incremental cost per additional responder on the primary outcome;3.to inform refinement and tailoring of the implementation strategies for different service settings.Secondary aims are:The study will use a stepped-wedge cluster randomised controlled trial (RCT) design, with Australian oncology and palliative care services as the units of randomisation. In this design, randomisation concerns the sequence in which services transition between experimental conditions rather than the condition to which they are allocated see Fig. . Each paWhile needing a longer timeline than a parallel cluster design, a stepped-wedge design has the following advantages for translational research: 1) the design controls for between-service variation in baseline practice; 2) statistical power is boosted by the opportunity to assess intervention effects in a pre/post comparison across services; and 3) assessment of longitudinal effects (i.e. sustainability) can occur in services that transition earlier .Ethics approval was granted by the South Western Sydney Local Health District Human Research Ethics Committee (HREC). Protocol modifications will be submitted to the HREC for approval, and modifications made to the trial registry information as needed.This protocol complies with reporting requirements outlined in the cluster RCT extension of the Consolidated Standards of Reporting Trials (CONSORT)  and StanServices will be selected to inform understanding of intervention effectiveness across services of differing geographic locations  and configurations of oncology and palliative care. Study sites are included in the trial’s entry on the Australian New Zealand Clinical Trials Registry.There will be two patient participant populations for this study. The first will contribute to primary outcome data, and the second to secondary outcomes. Because the study is funded by the National Breast Cancer Foundation (NBCF) of Australia, sampling will aim to recruit ≥60% patients with breast cancer. It is anticipated that breast cancer’s prevalence and this population’s proven willingness to participate in clinical trials  will makParticipant eligibility criteria will follow recommendations from the Methods for Researching End of Life Care (MORECare) initiative  by targePatients will be excluded if they have already participated in the study either at another service taking part in the trial or at the same service when it was in the control arm, or are documented as having cognitive impairment that would preclude capacity to give informed consent.Potentially eligible patients will be identified by the research team via a review of service pain screening data (see below), which will include information about their NRS score, whether they have opted out of being contacted, and their cancer status (completed by clinic staff). Patients will be telephoned at home, and the verbal informed consent procedure undertaken.Unpaid carers will be eligible if they: 1) are identified by a patient who has given informed consent to participate in the study as providing them with substantial emotional and practical support in an unpaid capacity; 2) are willing to provide verbal informed consent to participate; and 3) have sufficient spoken English proficiency to complete a survey and/or interview.Carers will be excluded if the patient for whom they provide care does not participate in any secondary outcome components.Service staff will be eligible to participate if they are: 1) employed on a permanent basis either full- or part-time at a participating service in a role that provides clinical care to patients with cancer pain or front desk administrative support; and 2) provide informed consent.Service staff will be excluded if they are working at a participating service on a casual or agency basis.Each participating service will first be included in the control arm and then transition to the intervention arm, defined as follows. Due to the pragmatic nature of the trial, no limit is placed on other interventions each service can undertake during the study period.We will compare the intervention with usual care plus the introduction of routine screening for pain where this is not already common practice. The rationale for including a screening system in the usual care arm is that this is already routine practice in some oncology and palliative care services across Australia.Management and clinicians at participating services will be made aware of the Australian online guidelines for ‘Cancer Pain Management in Adults’ and the study’s aim to test implementation of these. Services that are already utilising an electronic or paper-based symptom screening system will be asked to incorporate the study’s NRS for worst and average pain over the past 24 h. Where no screening system is established, services will be equipped with a paper-based system for symptom screening and providing individual patient reports for treating clinicians to refer to during consultations. A paper-based rather than electronic screening system has been chosen because a pilot study conducted by the current authors found that implementing electronic screening can be resource-intensive and logistically challenging . AcknowlWhile access to pain screening results and online guidelines will be unfettered, services will not be given strategies to encourage or support clinicians in using these.The control arm at each service will continue as long as necessary to recruit the target sample size.training phase, two clinicians at each service will take on the role of ‘clinical change champions’ to lead local implementation of the intervention with support from the project team. Two are needed to cover any periods of absence. Selection of clinical change champions will be conducted in partnership with managers at each service. Champions can be of any discipline and role provided they meet established criteria [At the beginning of a criteria .Champions will attend training at their service aimed at tailoring the intervention to local needs and contexts. Champions will be involved in administering the audit tool and feeding back data to staff in order to identify strengths and weaknesses at their service against recommendations in the guidelines. They will also be supported to identify barriers and facilitators to cancer pain management and helped to develop solutions. Champions will be invited to attend monthly teleconferences with champions at other services to create a community of practice that will enable knowledge sharing, knowledge creation and identity building . The degAlso during the training phase, all clinical and reception-desk staff will be given an overview of the guidelines and implementation resources by the champions at their service with support from the project team.During the training phase and for a period of three weeks afterwards, data will not contribute to outcome measurement to allow time for the intervention to become established as routine practice.intervention phase, the process for feeding back individual patient results from screening will be monitored, with medical teams receiving a summary report of screening data for each patient prior to consultation to inform management, and a copy filed in the medical record. The process by which this happens will vary across services according to local systems.During the Three implementation strategies will be used to address commonly reported barriers and facilitators in the most parsimonious way. Findings from a systematic review suggest that coverage of barriers, rather than number of strategies, may be important in successfully implementing guidelines . TherefoThe patient-level strategy includes a written resource to help patients report and self-manage their pain, support coordination and communication between patients and clinicians, and advocate for evidence-based person-centred care [red care . This rered care  and widered care . The selred care , 41. PatThe strategy selected for the clinician level is a spaced learning training module for clinicians of different disciplines aimed at improving knowledge of guideline recommendations and applying this within the context of person-centred care. Spaced learning will be delivered online using the QStream Healthcare Solutions platform. The spaced learning format has been shown to significantly improve knowledge and retention of guideline content in RCTs [ in RCTs . This ap in RCTs , 44. FurAt the service level, an audit and feedback mechanism has been chosen as the best strategy following evidence from a Cochrane systematic review that this strategy can lead to improvement in provider compliance with desired practice , includisustainability phase, service clinicians who are trained in the use of the audit tool will provide the research team with de-identified audit data on pain assessment and management for patients screened as having a severe (≥7 NRS) pain score to assess whether adherence to guideline recommendations has continued.During a The study period for each patient will be four weeks or until death, whichever is the shorter time. See Table The primary outcome will relate to both individual patient and cluster levels and concern the probability that patients at each service initially screened as having moderate-severe (≥5 NRS) worst pain will experience a clinically important improvement one week later, defined as a ≥ 30% reduction in their original rating.One week following positive screen is considered sufficient time to allow for comprehensive assessment and any new treatment regimens to become established. Pain over the past 24 h was chosen to balance the need to avoid recall bias with sampling a representative time window. The NRS is the optimal brief measure of pain severity based on compliance rates, responsiveness, ease of use and applicability . The NRSA 30% reduction in pain was selected as the minimal clinically important difference (MCID) based on recommendations for pain trials by the US Food and Drug Administration, which takes into account evidence that the number of NRS points needed for a MCID varies according to the baseline score .To minimise selection bias, the study will use an opt-out procedure for patients’ permission to obtain their contact details and telephone them one week later to measure the primary outcome. Upon contact, patients will be invited to give verbal informed consent to provide primary outcome data, and will remain at liberty to refuse at this time.For a flow diagram of recruitment of patients to the primary outcome component of this study, see Fig. Secondary outcomes will assume a MCID to be 0.5 standard deviation (SD), using an established rule of thumb for patient reported outcomes .Secondary outcomes for pain will be at the cluster level and relate to the potential for the intervention versus control arm to result in: 1) mean reduction for worst pain severity in patients with clinically significant (≥2 NRS) and moderate-severe (≥5 NRS) worst pain from screening to one, two and four weeks later; and 2) mean reduction for worst and average pain across all screenings, to give a population measure of effect.A waiver on patient consent has been authorised by the HREC to include de-identified pain screening data from all patients attending services during the control and intervention arms to avoid selection bias. However, informed consent will be required for participation in all other secondary outcomes, detailed as follows. The HREC has approved a verbal (rather than written) consent procedure for all outcomes except health service utilisation, for which written informed consent will be required using a standardised form developed by Medicare.Patient QOL will be measured at weeks one, two and 4 using the EORTC QLQ C15-PAL , a shortA MCID of 0.5 SD difference between control and intervention arms will provide a convenient single estimate that approximates to scale-specific MCIDs developed for the QLQ C15-PAL .The Health Education Impact Questionnaire (heiQ) will be administered at weeks one, two and 4 to evaluate patient empowerment. A version of the heiQ developed in Australia specifically for cancer will be used. The study includes scales measuring health service navigation, constructive attitudes and approaches and skill and technique acquisition . As wellThe Carer Experience Scale (CES) will be administered at weeks two and 4 to evaluate the intervention effect on unpaid carers in terms of their relationship with patients, support received and ability to carry on with their own lives .The implementation strategies evaluated by this study represent a complex intervention involving multiple interacting components . As suchService-level process measures are: screening rates, clinician training (via spaced learning and other initiatives), adherence to the guidelines, and documentation quality.Staff-level process measures are: the amount of time spent in training and on cancer pain screening, assessment and management by clinical staff and front desk administrative staff. Staff will be invited to complete an anonymous online survey that asks them their role at the service and three separate questions on how much time they spent on cancer pain screening, assessment and management during their last complete work day.Patient-level process measures are: number of consultations, multi-disciplinary input, primary care support, and indices of care recommended by the guidelines. Items of particular interest will be instances of screening, assessment, patient education, regular analgesia, breakthrough analgesia and management of side-effects (preventative and treatment). The audit tool (administered by trained personnel to standardise between arms and services) will assess participants’ clinical records retrospectively. Because it is often not documented in medical records, patients’ receipt of pain education will be measured by asking the patient at each time-point they contribute to secondary data collection.Patient variables will include demographics, details of cancer diagnoses, performance status  who participate in secondary outcome measurement will be invited to take part in interviews 4 weeks after initial screening. Interviews will use a focused question route and ask about informants’ experiences of pain assessment and management, self-management education, and perceived person-centredness and coordination of care.A sample of patients and carers  representatives from participating services will contribute as authors.N = 492), our study will have > 90% power to detect the main effect. The study will oversample by two services  and 18 patients per service (i.e. n = 100 at each service) to allow for drop-out.To assess the appropriate study sample size and compute study power, we used a computer simulation allowing for 20% dropout by both services and patients. Drawing on data from 1612 consecutive patients . To moreRandomisation will be conducted at a central office by a statistician (LL) not involved in the operation of the study. A random sequence will be generated using a computerised randomisation algorithm. Allocation will be based on clusters rather than individuals, and randomisation will be concerned with the time at which each service transitions from the control arm to training and intervention. Randomisation will occur prior to data being collected at each service. Due to the nature of the intervention, concealment of allocation is not feasible. Stratification will be unnecessary because each service will serve as its own control. Patients will be automatically allocated to control or intervention arms according to the current arm of their treatment service upon their first presentation.Randomisation will be conducted by the trial statistician (LL). Services will be enrolled by members of the project team prior to randomisation after a contract is signed by service managers. No concealment will be feasible for managers and clinicians due to the nature of the trial design and intervention. Because randomisation is concerned with the time at which each service will commence the intervention, individual patients and caregivers will be enrolled after randomisation but will be unaware of service allocation at the time of their enrolment.The nature of the intervention in this study renders blinding of clinicians impractical, and previous research suggests that uptake of guidelines in the control arm will be unlikely in the absence of targeted strategies of the kind to be introduced in the intervention arm . InformaFor the main analysis, linear mixed models  will be An economic evaluation will estimate the incremental costs and consequences of the intervention versus control arm. The primary outcome for the cost-effectiveness analysis will be the incremental cost per additional responder, with response defined as a clinically important improvement of 30% on a 0–10 NRS one week post-screening for those with moderate-severe (≥5 NRS) worst pain). The incremental cost per additional quality adjusted life years (QALY) will be the secondary outcome. Utility scores will be derived from the EORTC QLQ-C15-PAL and 5 additional items from the QLQ-C30 (mapped from QLQ-Utility ) and indInterview and focus group data will be transcribed verbatim and imported into NVivo 11 software for analysis. Analysis will use an integrative qualitative method designed specifically for informing health service interventions . This meThe Promoting Action on Research Implementation in Health Services (PARiHS) framework will be applied to analyses of interview/focus group data and the structural and process measures outlined above to consider the influences of evidence, context and facilitation on the success of the intervention .The protocol for the Stop Cancer PAIN Trial has been designed to balance the need for rigorous evaluation with the flexibility required by complex interventions . The proOne of the advantages of a stepped wedge design over parallel cluster RCTs is that a diversity of services can be included without compromising comparability because each cluster serves as its own control. Inclusion of heterogeneous services in the proposed study should enable generalisability of results to a large proportion of Australian oncology and palliative care services. Our qualitative sub-study and analyses of structural and process factors will provide useful insights into the requisite conditions for the intervention to succeed and modifications needed for different service models.The study’s methods are limited by a lack of blinding, which is necessitated by the nature of the design, intervention and outcomes. Standardised procedures for eligibility screening are designed to reduce the risk of selection bias that might arise from clinician and researcher knowledge of allocation. Logistic barriers will mean that sustainability assessment beyond the intervention arm period will be limited to audit data at the service level, rather than outcome measurement at the patient level. Sustainability of effects on patient and carer outcomes, therefore, will at best be inferred rather than directly observed. There is also a risk that practical issues relating to service availability and recruitment may make the randomisation schedule difficult to adhere to with regard to the order in which each cluster commences the control arm and transitions to the intervention . The maiIf implementation strategies are found to be cost-effective, they will be made available free-of-charge alongside the Australian guidelines for 'Cancer Pain Management in Adults' on the Cancer Council Australia Cancer Guidelines Wiki  to facilThe trial was prospectively registered on the Australian New Zealand Clinical Trials Registry on 23rd January 2015 with the trial identification ACTRN12615000064505; World Health Organisation unique trial number U1111–1164-4649. The primary sponsor is The University of Sydney. TL is the contact for public and scientific queries: Tim Luckett; T + 61 2 9514 4861; E tim.luckett@uts.edu.auI001/V 5, 5th April 2017.Decisions for the conduct of the trial are made by the Stop Cancer PAIN Trial Executive Committee . The trial is coordinated from IMPACCT  from the University of Technology Sydney. An Advisory Group meets twice yearly to identify synergies with other initiatives across Australia.


To examine the effectiveness of cryotherapy for reducing postoperative pain in patients who underwent exploratory laparotomy for gynecologic surgery. Patients who had indication for an exploratory laparotomy gynecologic procedure were selected by attending physicians to undergo abdominal surgery via low transverse skin incision. The participants were randomized into study and control groups with simple random sampling methods. Cold packs were applied at two hours after operation for 6 hours. The visual analog scale (VAS) score was recorded at two, 6, and 12 hours after operation. One hundred cases were recruited and then divided into study and control groups equally. The mean age of both groups was 43 years. There was no difference in demographics data of both groups. Half of the participants in both groups underwent hysterectomies. At two hours after surgery, both groups had similar VAS scores. The study group had a lower VAS score at 6 and 12 hours after surgery than the control group with statistical difference. Morphine consumption within 24 hours after surgery in both the study and control groups was 2.8±3.4 and 3.0±4.4 mg, respectively, with no statistical difference. However the registration time of the first morphine requirement in the study group was statistically more prolonged than that of the control group. The lengths of hospital stay in both groups were similar. There was no complication reported in this study. Cryotherapy can reduce postoperative pain. In this presented study the patients who underwent gynecologic surgery had improved pain relief and prolonged time for the first dose of the analgesic drug. Postoperative pain is a major concern of many patients. It is inadequately treated in as many as 30 to 50% of all postoperative patients . Tissue When patients' postoperative pain decreased, patients reported less complications, i.e., no atelectasis and bowel dysfunction, and less side effects from pain relievers. The most common medications given for postoperative pain are opioids and opioid derivatives. They are known to cause dizziness, sedation, nausea, vomiting, physical dependence, tolerance, and respiratory depression .Cryotherapy is a popular nonpharmacological intervention used to relieve pain following musculoskeletal injury, major surgical procedures, and vaginal delivery –9. FurthMany clinical studies studied the effectiveness of cryotherapy in postoperative pain reduction –9. In a More than 80% of the patients that underwent gynecological operations experienced severe pain . FurtherThe aim of this study was to compare the effectiveness of cryotherapy to that of standard postoperative pain management in gynecologic surgery with low transverse incision.TCTR20180226004). Patients with low transverse incision would be assigned cold pack compressions at the skin incision site compared to standard postoperative care.A randomized controlled study was conducted at Thammasat University Hospital, Pathum Thani, Thailand, to compare the effectiveness of cryotherapy and that of standard postoperative pain treatment after gynecologic surgery. Approval was obtained from the Human Ethics Committee of Thammasat University (MTU-EC-OB-1-192/60) and registered with the Thai Clinical Trials Registry  compression treatment. The cold pack in its own thin cloth bag was kept at -4°C ready for future use. The cold pack was then placed on top of the surgical wound at two hours after surgery. It was changed every two hours for two consecutive times. Patients were evaluated for complications of cryotherapy by verbal interviews at 30 and 60 minutes. Any complaint would be recorded. Patients were asked about their pain scores every two hours. The control group received standard postoperative care .Intravenous 3 mg morphine was given to any patients from both groups if their reported pain scores were equal to or greater than 6. Amount of morphine consumption and its possible side effects, namely, nausea, vomiting, itching, respiratory depression, and allergic reaction, were also recorded in the first 24 hours after operation.The sample size in this study was calculated from the standard deviation of the control group (SD = 2.89) from a pilot study . The alpha and beta were set at 0.01 and 0.05, respectively. A sample size of 100 patients (50 patients per group) was obtained from the calculation.The primary outcome was the visual analog scale (VAS) score at 6 and 12 hours after surgery. The starting time was defined as the time when incised skin was completely sutured. The VAS was ranked from score 0 (no pain) to 10 (worst pain). Secondary outcomes were morphine consumption within 24 hours after surgery, time for the first dose of the analgesic drug administered, length of hospital stay, and surgical site infection rate. p value less than 0.05.Data were analyzed by using the Statistical Package for the Social Sciences  for Windows, version 24. Continuous data were represented by mean and standard deviation. The VAS score was analyzed by repeated ANOVA. Categorized data were evaluated by the chi-square tests or Fisher exact test whichever appropriated. The level of statistical significance was set at aOne hundred women were enrolled into the study and control groups. Each group was composed of 50 cases . There wLength of transverse surgical incision in both groups regardless of their procedures was around 13 cm without statistical significance . At two Morphine consumption within 24 hours after surgery in both the study and control groups was 2.8±3.4 and 3.0±4.4 mg, respectively, with no statistical difference. However the registration time of the first morphine dose requested in the study group was statistically longer than that of the control group  as presented in Cryotherapy for pain relief has been used for many years in the treatment of localized tissue trauma. The temperature reduction of the soft tissue by 10 to 15°C was reported to decrease local metabolism and oxygen requirement. Soft tissue temperature reduction also induces peripheral blood vessels constriction, resulting in the reduction of tissue swelling, bleeding, bruising, and localized pain [In the present study, cryotherapy reduced postoperative pain in patients who underwent gynecologic surgery at 6 and 12 hours compared to the control group. Cryotherapy in our study was an applied cold pack to the surgical site for 6 consecutive hours after operation. Its effect lasted long until 12 hours after surgery.p<0.05) [There are many clinical studies that studied the effectiveness of cryotherapy –9. The rp<0.05) . Their rp<0.05) but there was no difference in the mild pain score. Opioid consumption, hospital stay, and wound infection showed no statistical difference between both groups [Wanlayanee and coworkers studied 28 patients who underwent benign gynecologic surgery. Gel packs were applied at two hours after operation for 20 minutes. Gel pack application showed statistically significant result in postoperative pain reduction when pain was divided into moderate to severe and mild pain intensity at 6 hours after surgery. Their patients who had moderate to severe pain in the control and study group were 11 and 8 (h groups . In the The mean morphine consumption within 24 hours after surgery in the control and study groups was 3.02±4.52 and 2.8±3.35 mg, respectively, without statistical significance. The amount of morphine consumption was not a primary objective of this current study.The strength of our study was that it was a randomized controlled trial and the surgeons were blind to the assigned treatment groups. Multiple primary and secondary outcomes measured were obtained for comparative analysis. Our limitation was the unblinded intervention.Cryotherapy can reduce postoperative pain. In this presented study patients who underwent gynecologic surgery had improved pain relief and prolonged time for the first dose of the analgesic drug. The use of cryotherapy can improve postoperative pain control. Cryotherapy, in our opinion, should be widely used in postoperative pain control because it is a noninvasive mode of operation with a very effective cost, no complication, and a very favorable patient report.


Most patients (58.9%) indicated the involvement of more than six body areas affected during pain crisis. Severe pain was described by more than half the patients (55.6%), while moderate pain was reported by 31.1%. Most patients described their pain by sensory, affective, and temporal words. The number of painful areas, pain intensity, and use of descriptive pain words was correlated and interpreted by age, BMI, school absence, and number of surgeries. Results of this study could provide guidance to healthcare providers to improve current practices for SCD pain management in order to improve health outcomes and patients’ satisfaction.Management of sickle cell pain in adolescent and pediatric patients is inadequate, and the employment of proper management guidelines and practices are highly variable among different regions and populations. APPT, the multidimensional adolescent pediatric pain tool, promotes optimal pain management and introduces best practical guidelines for pain management. The goal of this study is to assess pain and pain management among young patients diagnosed with sickle cell disease (SCD) by introducing the APPT as a tool for pain management, and analyze factors contributing to pain management. Information relevant to demographic data, SCD characteristics, APPT assessment, and satisfaction of patients regarding pain management were collected using a structured questionnaire. Results showed that SCD is highly associated with gender ( The global burden of hemoglobin disorders cannot be ignored; they contribute to about 3.4% of mortality in children aged less than five years ,2. WorldSickle cell disease (SCD) is a worldwide, common hereditary blood disorder affecting red blood cells . SCD, a SCD displays several symptoms and complications including chronic anemia, acute chest syndrome, stroke, renal dysfunction, susceptibility to bacterial infections, and pain crisis ,7. Pain Pain crisis is a major clinical manifestation of SCD . Proper Pain management at hospitals in Jordan utilizes both opioids and/or non-opioids for management in SCD pain, and to the best of our knowledge, SCD pain management satisfaction among young patients has not been previously evaluated. Therefore, lack of understanding of the characteristics of SCD pain may lead to both over and under treatment of pain. The purpose of this study is to introduce a multidimensional pain assessment tool (APPT) with the hope of optimizing pain management, improving patient’s satisfaction and boost pain relief outcomes. The objective of this study is to examine SCD pain and pain management by assessing sickle cell pain in adolescent and pediatric patients using clinical practical guidelines, and to explore patients’ satisfaction with their current pain managements. This was a descriptive, cross-sectional study, conducted at three hospitals in Jordan between October 2016 and February 2017.Approval was obtained from Jordan University of Science and Technology (number 20150327), and from the Ministry of Health Institutional Research Board (IRB).Out of 125 patients approached, 90 patients completed the survey and record taking. Data was collected from three governmental hospitals located at northern and central regions in the country: Princess Rahma , Al Basheer  and Princess Basma  hospitals in Jordan. The research goals and methods were explained to the patients and their legal guardians. Patients who agreed to participate in the study were handed consent forms to sign. The questionnaire was administered and collected by the researcher in a semi structured (interview) fashion with the patients or their legal guardians. n = 15) in order to consider any modifications to the questionnaire before the start of large-scale data collection. The final version of the questionnaire took into consideration the results of the pilot study. The pilot questionnaires were not considered in the final data analysis. The final version of the questionnaire employed for this study was composed of four sections, which included demographics, disease characteristics, pain assessment and management in hospitals, and patient satisfaction regarding pain management.After an extensive literature review, the questionnaire was developed and modified by the authors taking into consideration previous work published in literature regarding the same topic. A pilot study was conducted at the beginning of the study . Adolescent Pediatric Pain Tool (APPT) is a multidimensional pain instrument for adolescent and pediatric patients that assesses pain status by the location or body areas, pain intensity, and description of pain using words divided into sensory (describe pain they can feel), affective (describe pain related emotions), and temporal (described pain in relation to time) categories.Pain intensity was measured by numerical scale for patients five years or older, while for the case of younger patients (less than five years) the parents gave their estimates of their children’s pain intensity. This numerical scale was divided into three categories: mild (0–3), moderate (4–6), and severe pain (7–10). In addition, patients were asked about pain management during hospital stay, and the duration of time it took to get pain relief was recorded.Patients were asked specific questions which were developed to analyze and assess their satisfaction regarding pain management in hospital settings.2 test of independence was used. To assess correlations between continuous variables, Spearman’s correlation test was applied. Findings were considered statistically significant when p < 0.05. Data analysis was performed using SPSS version 20.0 . As the continuous variables were not normally distributed, non-parametric statistical tests were applied. Continuous variables were presented as medians and interquartile ranges (IQRs) expressed by the 25th and 75th percentiles. Categorical variables were presented as the frequency and percentages. To assess associations between categorical variables, Pearson’s χA total of 90 questionnaires were completed; this amounted to a response rate of 72%.The demographic data for patients in this study are summarized in 3/mm3 . The median red blood cell (RBC) count and hemoglobin (Hg) concentration were 3.1 × 106/mm3 and 8.2 mg/dL, respectively. Most patients presented with high WBC count (63.3%) and low RBC count (84.4%). All patients had low Hg levels and the vast majority had blood transfusions. Respiratory disease was the most common comorbidity reported.Details concerning the characteristics of the SCD are summarized in 2 = 5.230, p = 0.022, 2 = 8.897, p = 0.012, 2 = 6.195, p = 0.013, Chi square analysis showed a significant association between the types of SCD disease and gender. More females had the HbSS genotype , while males suffered more of the beta thalassemia genotype (HbSβ)  and non-steroidal anti-inflammatory drugs (NSAIDs) (74.4%), regularly at home for pain management. Almost all patients reported regular use of folic acid (97.8%). Indigestion was the most frequent adverse effect indicated by patients (6.7%). List of medications used and side effects as described by the patients are shown in Pain crisis was the most common cause for hospital admission (93.3%). The median number of pain crisis among the study sample was 5 episodes per patient was . Pain was either provoked (65.6%), or sudden (34.4%). Top provoking factors include extreme cold (81.1%), extra movement or hard work (41.1%), exposure to heat or sun (23.3%), and psychological factors (17.8%). Several symptoms accompanying pain crisis from SCD were reported by patients. The most common were loss of appetite (82.2%), joint pain (81.1%), jaundice (77.8%), fever (80.0%), feeling tired (67.8%), palpitation (56.7%), and shortness of breath (50.0%).Pain characteristics with SCD were evaluated and assessed via APPT. Number of body areas with pain crisis was reported per patient from (0–21) sites, with a median of six sites. About 53 patients (58.9%) had pain crisis in six or more body sites, while 37 patients (41.1%) had pain in less than six sites. Most frequently, pain was in the lower back, chest, hip, abdomen and extremities. Pain intensity was determined by numerical pain scale (NPS); NPS gives objective values of pain as reported by the patients from 0 (no pain) to 10 (most severe pain). All patients reported a degree of pain intensity. The median was 7 ; 12 patients had mild pain (13.3%), 28 patients reported moderate pain (31.1%), and 50 patients had severe pain (55.6%). Patients described their pain by at least one sensory word per patient such as pins, needles, squeezing, or stabbing; one affective word per patient such as annoying, crying, and screaming; and one temporal word per patient such as slowly, off and on, and continuous as summarized in Bivariate correlation analysis is shown in All patients reported pain relief at the hospital (100%). Medications used at hospital for pain management were either non-opioids for 79 patients (87.8%), or combination of opioids with non-opioids for 11patients (12.2%). The time to pain relief ranged from 10 min to more than 24 h. However, most patients 68  required over 24 h for complete pain relief.Most patients  were satisfied with pain management at their hospitals, as well as services from with healthcare providers (HCPs). The majority  of patients said that medications used were explained to them thoroughly by HCPs.Until a cure for sickle cell disease is discovered, patients, particularly children will continue to suffer from the pain that accompanies this disease. As healthcare providers, we are all invested in finding ways to assess and treat this pain in an efficient and timely manner. In this study, pain crisis was the main reason for hospital admissions 93.3%), in accordance with similar percentages in other published reports ,23,25,263.3%, in This study employed the APPT, a systemic method for describing the characteristics of pain and provides more objective measures, such as number of painful body areas, pain intensity, and description of pain using sensory, affective, and temporal words . The intMedications used for pain management at hospitals are either non-opioids and/or opioids. Suggested guidelines for management of SCD pain include the use of opioid and non-opioid medications in addition to supportive treatment ,12,21,24Most patients (90.0%) were satisfied with pain management, which was surprising considering that pain relief took over 24 h for most patients. We might explain this by the good patient phenomenon; the patients feel like saying good things about healthcare providers out of fear or shyness . SCD patIn conclusion, pain crisis continues to play an integral part in increasing morbidity and mortality among patients with SCD. Understanding the nature of SCD and pain crisis by health care providers will be instrumental in offering the best managements of pain. Thus, early pain assessment and management can help in reducing morbidity and mortality. The APPT is widely used among pediatric populations with a variety of clinical conditions. Use of the APPT provides a lot of information that aids in understanding of the development of pain over time. In addition, APPT can be used in acute pain for both hospitalized and non-hospitalized adolescent and pediatric patients. APPT not only measures pain intensity, but is also a multidimensional pain-assessment tool for those experiencing complex pain situations. Multidimensional pain-assessment tools promote cooperation between clinicians and patients. Assessment tools should be recommended for all pain situations, and healthcare providers should be encouraged the use these tools. Cross sectional study allowed for one-time only measure of outcome and exposure thus limiting examination of cause and effect.Even though the sample size was decent, more participants would have given more strength to the study.Would have liked to add more questions to the satisfaction with health care section to evaluate parameters that further contribute to knowledge regarding quality of life such as catastrophizing, acceptance, and self-efficacy.The data in this study seemed to call for multivariate analysis; however, this was not possible due to the sample size used in the study and study design.


Additionally, pain scores at rest during POD 0–3 were not significantly associated with preoperative kidney function. In conclusion, our results suggest that patients with mild to moderate CKD (stage 2–3) did not require reduction of opioid analgesics during POD 0–3, compared to patients with normal preoperative kidney function. Only patients with severe CKD (stage ≥ 4) might require a slight reduction of opioid analgesics.The amount of reduction in opioid doses and its effect on postoperative pain outcomes in chronic kidney disease (CKD) patients in the perioperative setting remains unclear. This study aimed to investigate differences in postoperative pain outcomes after major laparoscopic surgery between patients with CKD and those with normal preoperative kidney function. Medical records of patients who underwent laparoscopic major abdominal surgery from January 2010 to December 2016 were retrospectively reviewed, and 6,612 patients were finally included. During postoperative day (POD) 0–3, patients with an estimated glomerular filtration rate (eGFR) < 30 mL min The most commonly used method of postoperative pain control is systemic opioid analgesia3. A recent study reported that opioids are commonly used until postoperative days (PODs) 4 to 15 among patients after common surgical procedures4. However, opioids are associated with a variety of known adverse effects5 and should be used with caution in patients who are more vulnerable to these adverse effects. Patients with chronic kidney disease (CKD) are particularly at risk of developing serious adverse effects of opioids.It is reported that about 80% of all surgical patients experience postoperative pain−1 1.73 m−2 6, is a global health problem with a worldwide prevalence of 8% to 16%7. Because CKD patients have a reduced ability to clear drugs through the kidney, the dose of opioids should be appropriately reduced to avoid adverse effects in these patients8. A systematic review conducted as part of the European Palliative Care Research Collaborative opioid guidelines project9 reported that, among opioids, morphine has the highest toxicity rate in CKD patients, whereas alfentanil, fentanyl, and methadone have the lowest toxicity rates. However, that study only analysed data from chronic cancer patients and did not include patients with perioperative or acute pain9. Although one study recommended that the dose of transdermal fentanyl should be reduced by 50% in CKD patients10, there is limited evidence regarding the use of fentanyl for postoperative and acute pain control in patients with CKD11. Thus, there is a lack of information regarding the impact of impaired renal function in patients with CKD on requirement for opioids and on pain outcomes in the perioperative setting.CKD, which is defined by an estimated glomerular filtration rate (eGFR) below 60 mL minTherefore, this study aimed to investigate differences in postoperative pain outcomes, including opioid consumption and pain scores, after major laparoscopic surgery, between patients with CKD and those with normal kidney function. Our hypothesis for this study was that a correlation exists between the degree of renal impairment and opioid consumption in patients with CKD stages 1–5, after major laparoscopic surgery−1 1.73 m−2 (25.8). There were no life-threatening opioid-related complications  among the study population.A total of 20,800 patients at the Seoul National University Bundang Hospital (SNUBH) underwent a laparoscopic surgical procedure between January 1, 2010 and December 2016. Of these, 856 patients were excluded for age younger than 20 years, 1,053 were excluded for emergency surgery, 1,390 were excluded for single-port laparoscopy, 9,571 were excluded for surgery lasting less than 2 hours, 343 were excluded for receiving a continuous infusion of remifentanil or dexmedetomidine during the first three PODs, 8 were excluded for being discharged before the third POD, 25 were excluded for undergoing additional surgery during the first three PODs, 42 were excluded for intraoperative conversion to open laparotomy, 96 were excluded for undergoing simple appendectomy or cholecystectomy, 58 were excluded due to preoperative chronic opioid usage, and 746 were excluded for missing or incomplete medical records. As a result, 6,612 patients were included in the final analysis. A flowchart of the patient selection process is shown in Fig. −2), American Society of Anesthesiologists (ASA) physical status, some preoperative comorbidities , surgery time, propofol-based total intravenous anaesthesia (TIVA), intraoperative magnesium infusion, years of surgery, preoperative eGFR were selected with a criterion of P < 0.2 in the univariate model. The results of the multivariate generalized linear regression analysis, including the variables selected from the univariate model, are shown in Table −1 1.73 m−2 had a significant 3.5% lower morphine equivalent consumption on PODs 0 to 3 than the group with a preoperative eGFR ≥ 90 mL min−1 1.73 m−2 . However, the patients with preoperative eGFR: 60–90 mL min−1 1.73 m−2 and 30–60 mL min−1 1.73 m−2 were not associated with differences in morphine equivalent consumption on POD 0–3 .Table P < 0.001), body mass index (kg m−2) , cancer , surgery time (min) , propofol-based TIVA , intraoperative magnesium sulphate infusion  were significantly associated with morphine equivalent consumption during POD 0–3.Additionally, male sex . Among the adjuvant analgesics, acetaminophen consumption during the first three PODs was not significantly associated with preoperative eGFR (P > 0.05); however, ketorolac consumption during the first three PODs was 33.8% lower in the group with an eGFR of 30–60 mL min−1 1.73 m−2 group, compared with the group with a preoperative eGFR ≥ 90 .Table −1 1.73 m−2) than in those with normal kidney function (eGFR ≥ 90 mL min−1 1.73 m−2) during the first three days after major laparoscopic surgery, while it was not significantly associated with mild to moderate CKD (eGFR 30–90 mL min−1 1.73 m−2). In addition, there were no significant differences in NRS pain scores at rest between the patients with CKD and those with normal kidney function during the first three days after major laparoscopic surgery. As a result, this study suggests that preoperative kidney function status did not affect pain outcomes after major laparoscopic surgery, except in severe CKD patients with eGFR < 30 mL min−1 1.73 m−2. Furthermore, considering that the difference in morphine equivalent consumption between severe CKD patients with eGFR < 30 mL min−1 1.73 m−2 and patients with normal kidney function (eGFR ≥ 90 mL min−1 1.73 m−2) was just 3.5%, the clinical significance is questionable.This study showed that opioid consumption was significantly lower in patients with stage 4 or 5 CKD , and analysed their opioid consumption during POD 0–3. Our findings are novel, because no study has evaluated the effect of preoperative CKD stage on the postoperative pain outcome in detail.A recent study by Binhas 13, it is possible that even a reduced dose of fentanyl may have resulted in prolonged analgesic effects in CKD patients. Second, all patients received an IV PCA for pain control, which enabled them to titrate their postoperative pain14. Thus, an opioid dose reduction in CKD patients was unlikely to result in insufficient pain control.Even though the morphine equivalent consumption in our study was 3.5% lower in the patients with severe CKD than in those with normal kidney function, there was no significant difference in postoperative NRS pain scores at rest during the first three PODs between the two groups. There are two reasons that may explain this similarity in pain scores between the groups. First, it is possible that the serum opioid concentration was maintained at a similar level between patients with CKD and those with normal kidney function, regardless of dose reduction, due to delayed excretion of opioids in CKD patients. Moreover, the most commonly used opioid in this study was intravenous (IV) patient-controlled analgesia (PCA) fentanyl and the elimination of fentanyl can be delayed in CKD patients. Because the metabolites of fentanyl are known to be inactive and nontoxic15. However, a recently updated 2017 guideline reported that CKD patients do not show a significant serum accumulation of IV fentanyl16, suggesting that it is not necessary to reduce the dose of IV fentanyl for opioid-naïve CKD patients. The protocol at the SNUBH renders a reduction of the IV PCA fentanyl dose for CKD patients by about 25% to 50%, according to the patient’s eGFR. However, because patients were able to self-titrate and receive other opioid analgesics, the morphine equivalent consumption in severe CKD patients was only 3.5% lower than in patients with normal preoperative kidney function in the present study. Thus, our results suggest that it is not necessary to reduce the IV PCA fentanyl dose by more than 25% for CKD patients.One notable finding of this study pertains to the appropriate dose reduction of IV fentanyl for CKD patients. According to a 2009 guideline, the dose of most opioids, including IV fentanyl, should be reduced by 25% for patients with an eGFR between 10 and 5017 or propofol-based TIVA18 for laparoscopic surgeries. This study showed that intraoperative magnesium sulphate infusion resulted in a significantly lower morphine equivalent consumption (about 8.4%) and propofol-based TIVA resulted in a significantly lower morphine equivalent consumption (about 13.5%) during the first three PODs, which is in line with the findings of previous studies21. This suggests that propofol-based TIVA or magnesium sulphate infusion should be routinely considered for CKD patients. Additionally, surgery time or cancer were associated with morphine equivalent consumption during POD 0–3 in this study. This can be explained by an assumption that more complex and longer duration of surgical procedures are associated with more severe pain than simple surgical procedures. Preoperative BMI is another interesting factor associated with postoperative pain in this study. There were some reports that preoperative BMI was not associated with postoperative pain23; however, according to our study findings, there was positive association between preoperative BMI and morphine equivalent consumption during POD 0–3. At our institution, physicians did not tend to prescribe additional opioids in patients with lower BMI, which affected the results of this study. Therefore, further study is needed to confirm the association between BMI and postoperative pain outcomes at our institution.Another notable finding of this study is that we identified methods that can reduce postoperative pain in CKD patients, including the use of propofol-based TIVA. For several years, the SNUBH has used either an intraoperative magnesium sulphate infusionThis study has a few limitations. First, there is a possibility of selection bias due to the nature of a retrospective cohort design. In order to minimize the risk of selection bias, we used a medical record technician who was blinded to the purpose of this study. Second, this study was performed at a single centre, which may limit the generalizability of these findings. Third, most of the opioid analgesia used in this study was IV PCA fentanyl and the use of additional opioids  necessitated the application of a standard conversion ratio, which may have reduced the accuracy of these results. Fourth, the patients’ pain scores at rest were assessed by many different nurses over a period of seven years, which makes it difficult to ensure the accuracy of these scores. In addition, this study did not evaluate NRS pain scores at movement during POD 0–3, which limits the results of this study. Finally, we only focused on laparoscopic abdominal surgery rather than other surgeries, such as laparotomy, thoracotomy, or amputation, which could induce higher postoperative pain than laparoscopic surgery. Therefore, the results of this study might be restricted in its application to other surgeries.In conclusion, our results suggest that patients with mild to moderate CKD (stage 2–3) did not require reduction of opioid analgesics during POD 0–3, compared to patients with normal preoperative kidney function. Only patients with severe CKD (stage ≥ 4) might require a slight reduction of opioid analgesics.This retrospective cohort study was approved by the institutional review board of the SNUBH . The requirement for obtaining informed consents was waived due to the retrospective study design, and this manuscript adheres to the applicable STROBE guidelines. The medical record technician who collected patients’ demographic, clinical, and surgery-related data was blinded to the purpose of this study.24, discharge before POD 3, additional surgery during the first three PODs, intraoperative conversion to open laparotomy, continuous infusion of remifentanil or dexmedetomidine during the first three PODs, preoperative chronic opioid usage, and incomplete or missing medical records.The medical records of patients aged 20 years or older who underwent elective, major laparoscopic surgery at the SNUBH between January 1, 2010 and December 31, 2016 were analysed. Major laparoscopic surgery was defined as any laparoscopic surgical procedure that lasted for more than 2 hours and involved resection of an intraperitoneal organ. Simple appendectomy and cholecystectomy were excluded, even if the duration of surgery was longer than 2 hours. The exclusion criteria also included emergency surgery, single-port laparoscopy (which is known to cause less pain)During the study period, experienced surgical teams at the SNUBH proficiently performed laparoscopic resections of major intraperitoneal organs . Most patients received either balanced anaesthesia with desflurane and remifentanil or total intravenous anaesthesia (TIVA) with propofol and remifentanil.Most patients received IV PCA during the first 2 PODs. Most commonly, the IV PCA contained 8 to 12 µg/mL of fentanyl in normal saline. The background infusion rate (0.8–1.2 mL/h) and bolus dose (0.5–1.5 mL) were adjusted based on the patients’ underlying disease and kidney function. In general, the background infusion rate and bolus dose were reduced by 25% to 50% in patients with low baseline kidney function. After the IV PCA was discontinued, most patients were prescribed an additional opioid analgesic  based on the physician’s judgment or patient request. Adjuvant analgesics, such as acetaminophen and ketorolac, were also used for postoperative pain control. In general, surgeons at the SNUBH did not perform local anaesthetic infiltration of the wound site during the study period.−1) test is performed within one month of surgery as part of the routine preoperative laboratory screening for all elective surgical procedures at the SNUBH. We computed each patient’s preoperative eGFR using this baseline serum creatinine value and the Modification of Diet in Renal Disease Formula25: eGFR (mL min−1 1.73 m−2) = 186 × (preoperative serum creatinine)−1.154 × (age)−0.203 × .A serum creatinine  at rest by registered nurses at 4- to 6-hour intervals and at least 5 times a day. The mean NRS pain scores at rest were computed for PODs 0, 1, 2, and 3. The total opioid consumption, including IV PCA and additional opioid analgesics used on PODs 0 to 3, were computed using the oral morphine equivalent consumption and summed. A standard conversion ratio was used for the conversion and calculation−1 1.73 m−2).The primary endpoint measured in this study was the morphine equivalent consumption during POD 0–3 according to the preoperative kidney function status. The secondary endpoints measured in this study were NRS pain scores and adjuvant analgesic consumption during the first three days after major laparoscopic surgery according to the preoperative kidney function status. We classified the preoperative kidney function into four categories . For secondary endpoints, we also performed the same multivariate generalized linear regression analysis with six postoperative outcomes (NRS pain score at rest on PODs 0 to 3 and use of acetaminophen and/or ketorolac on PODs 0 to 3) as the dependent variables. Results are presented as exp. regression coefficient and 95% CI, and there was no significant multi-collinearity between variables in any of the multivariate generalized linear regression models . Additionally, Pearson chi-square statistics were used to test goodness of fit of multivariable models. All statistical analyses were performed using SPSS software , and statistical significance was set at P < 0.05. Considering that the mean (SD) morphine equivalent consumption during POD 0–3 was 516.6 (303.3) mg in this study, 143 patients were required in each group to detect 100 mg of difference in the morphine equivalent consumption during POD 0–3 between patients with normal kidney function (eGFR ≥ 90 mL min−1 1.73 m−2) and those with CKD (eGFR < 90 mL min−1 1.73 m−2) with a 0.05 chance of type 1 error and 80% power.Patients’ baseline characteristics are presented as number and percentage or mean value and SD. We examined the normality of distribution in dependent variables, such as morphine equivalent consumption, NRS at rest on POD 0–3, acetaminophen consumption, and ketorolac consumption, using the Kolmogorov-Smirnov test. After confirming that these variables did not follow a normal distribution, we decided to perform generalized linear regression analysis. First, we investigated variables associated with morphine equivalent consumption on PODs 0 to 3 using univariate generalized linear regression analysis. In this generalized linear regression model, a gamma distribution was assumed for the dependent variable , and the log link function was used. The variables with Supplmentary table 1. Equianalgesic opioid conversion table1