To investigate the incidence of and risk factors for moderate to severe pain during the first 24 hours after laparoscopic bariatric surgery.  This retrospective study included morbidly obese patients who underwent laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass at a single institution between June 2016 and July 2018. Demographic, clinical, operative, and postoperative pain data from the postanesthesia care unit (PACU) and ward were analyzed. Intravenous patient-controlled analgesia (IV-PCA) was commenced before PACU discharge. 2, and 69% were female. The incidence of moderate to severe pain was 75%. Moderate to severe pain during the first 24 hours was associated with young age, female sex, postoperative administration of NSAIDs, first pain score greater than 3 on arrival at the PACU, and inadequate pain control at PACU discharge. A multivariate analysis revealed that inadequate pain control at PACU discharge was the only factor independently associated with moderate to severe pain during the first 24 hours postoperatively (p=0.011). From PACU discharge to the end of postoperative day 3, moderate to severe pain at the end of each 24-hour period was a significant predictor of moderate to severe pain in the subsequent 24-hour period .  Ninety-seven patients were included. The mean age was 38.60 ± 12.27 years, and the mean BMI was 45.04 ± 8.42 kg/m Moderate to severe pain was experienced by 75% of patients undergoing laparoscopic bariatric surgery and receiving IV-PCA after PACU discharge. Inadequate pain control at PACU discharge was the only independent risk factor for moderate to severe pain during the first 24 hours postoperatively. Pain management is challenging in morbidly obese patients . As the Intravenous (IV) patient-controlled analgesia (PCA), a pain management strategy that allows patients to titrate their own opioid demand within the analgesic corridor, minimizes the incidence of side effects like OIVI , 7. IV-PThe present study aimed to investigate the incidence of and risk factors for moderate to severe pain during the first 24 hours postoperatively in morbidly obese patients who had undergone laparoscopic bariatric surgery and received postoperative IV-PCA before discharge from the PACU.This retrospective study included morbidly obese patients who underwent either laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass at a single, large, tertiary referral center between June 2016 and July 2018. Patients were excluded if IV-PCA was not started postoperatively, or if the data relating to their pain scores or the administered analgesics were missing. The study protocol was approved by the Institutional Review Board of our institution.Records from both the ward staff and the acute pain service were reviewed. The following data were collected: age; sex; BMI; American Society of Anesthesiologists classification; the presence and severity of OSA, diagnosed from the results of a sleep test as mild (Apnea-Hypopnea Index (AHI) ≥5, but <15), moderate , or severe (AHI ≥30); the presence of continuous positive airway pressure use in patients with OSA; and tobacco use (nonsmoking indicated that the patient had stopped using tobacco at least 30 days preoperatively). The surgical data collected were: type of laparoscopic bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy), concomitant surgical procedures, and operative time.As to information from the PACU, the pain scores at the patients' arrival and discharge and the details of all analgesics given were collected. All patients achieved at least 9 out of a maximum possible score of 10 on our hospital postanesthetic recovery scoring system before discharge from PACU. The scoring elements were movement ; respiration ; hemodynamics ; consciousness ; and color .The pain scores and details of all analgesic drugs administered in the period between the PACU discharge and 1 day after discontinuation of the PCA were obtained from ward staff and acute pain service records. Pain severity was rated using a 0–10 numeric rating scale (NRS): 0 indicated no pain, 1–3 mild pain, 4–6 moderate pain, 7–10 severe pain, and 10 maximal pain. Inadequate pain control was defined as moderate to severe pain on the previous day; as the present study focused on the first 24 hours postoperatively, inadequate pain control was defined as moderate to severe pain in the PACU. Nursing ward staff recorded the patient pain score every 4 hours, while the acute pain service recorded the pain score both at rest and during movement once a day or during a follow-up check after adjusting the analgesic regimen. The moderate-to-severe pain group comprised patients that had an NRS >3 at any assessment time during the first 24 hours postoperatively.All morbidly obese patients who underwent laparoscopic bariatric surgery were prescribed IV-PCA with the setting of bolus morphine 1 mg, a lockout of 5 min, and a 4 h-maximum dose of 30 mg. The daily PCA demand, delivery counts, and cumulative dose were recorded. The dosages of all opioid analgesics were converted to IV morphine equivalents  . A demanThe sample size was calculated based on a previously reported incidence of 70% for moderate to severe pain in patients who had undergone laparoscopic bariatric surgery . Using at-test. Variables with a p value <0.20 in the univariate analysis were included in the multivariate analysis. A p value <0.05 was regarded as statistically significant.All statistical analyses were performed using PASW Statistics for Windows, version 18.0 . Continuous data are presented as the mean ± standard deviation, while categorical data are shown as number and percentage. Data were tested for normal distribution using the Kolmogorov–Smirnov test. As to the univariate analysis, the association of the categorical variables with moderate to severe pain was assessed by the chi-squared test, while the association of the continuous variables with moderate to severe pain was assessed by Student's Ninety-seven patients were included. The mean age was 38.60 ± 12.27 years, and the mean BMI was 45.04 ± 8.42 kg/m2, and 69% were female. The incidences of moderate to severe pain drawn from the records of the acute pain service and the ward staff are presented in There were no significant differences in the demographic and surgical data of the moderate-to-severe pain group versus the no-or-mild pain group . There tp=0.038). By comparison, the median pain scores at discharge were 3 (0–6) vs 3 (0–7), respectively (p=0.103). The multimodal data for the pre- and intraoperative periods revealed that two patients (20.6%) received a premedication ; all patients had wound infiltration with local anesthesia, using 20 ml of 0.5% bupivacaine; one patient received 50 mg of ketamine intraoperatively; and three patients received a bilateral quadratus lumborum block. Only inadequate pain control at PACU discharge was significantly more frequent for the moderate-to-severe pain group than for the no-or-mild pain group. Postoperative NSAID usage tended to be more common in the moderate-to-severe pain group, but the intergroup difference was not significant. The amount of morphine required during the first 24 hours was 20.60 ± 15.77 vs 29.17 ± 18.86 mg (p=0.44) for the no-or-mild pain and the moderate-to-severe pain groups, respectively.Data relating to the patients' pain scores and analgesic drugs during the intraoperative, PACU, and postoperative periods are detailed in p < 0.2; Tables The univariate analysis revealed that the two groups significantly differed regarding age, female sex, postoperative NSAID usage, patients with NRS >3 on arrival at the PACU, and inadequate pain control at PACU discharge (p=0.011), at the end of the first 24 hours postoperatively (p < 0.001), and at 48 hours postoperatively  of moderate to severe pain in morbidly obese patients after laparoscopic bariatric surgery. In 1997, it was proposed that less than 5% of patients should experience pain after surgery by 2002ent care .Several studies have reported that younger age and female sex increase the risk of postoperative pain –16; howeMultimodal analgesia combines more than one type of analgesic to achieve pain control, while simultaneously reducing opioid consumption and opioid-related side effects. Multimodal analgesia regimens are the core of Enhanced Recovery after Surgery protocols . In the The multivariate analysis revealed that the only independent risk factor for pain after laparoscopic gastric bypass surgery was inadequate pain control upon PACU discharge. In our study, inadequate pain control was defined as an NRS >3 during the previous day . IV-PCA IV-PCA is not suitable for all patients. Optimal pain control requires the tailoring of treatment to the individual. The optimal bolus dose is that which results in good pain relief with minimal adverse effects. Therefore, the initial dose may need to be adjusted so that IV-PCA meets the requirements of each individual patient. IV-PCA is not a “one size fits all” or “set and forget” therapy . We alsoAlthough we found no significant differences in the postoperative complications of the groups, inadequate postoperative pain control has previously been associated with immune deficiency, slower wound healing, and the development of chronic pain . MoreoveThis study has some limitations. Firstly, this was a retrospective study that analyzed data from a single center. Furthermore, we had no information as to whether patients were trained in how to correctly use IV-PCA. Future research should attempt to identify barriers to the effective management of acute pain, and the consequences of inadequate pain management in morbidly obese patients.The incidence of moderate to severe pain in patients who underwent laparoscopic bariatric surgery and received IV-PCA after PACU discharge was 75%. Inadequate pain control at discharge from the PACU was the only independent risk factor for moderate to severe pain during the first 24 hours postoperatively. Caregivers should improve pain management in this patient population to improve the level of patient care.


The present study is a retrospective study.Axial symptoms are frequently encountered complication after laminoplasty. Some studies have reported the influencing factors and preventive measures of axial symptoms after laminoplasty. However, impact of different laminae open angles on the postoperative axial symptoms remains unclear.The objective of the present study was to explore the effect of different laminae open angles on postoperative axial symptoms and to discuss the possible mechanisms of the impact of different open angles on axial symptoms.We retrospectively analyzed 124 patients with multilevel cervical compression myelopathy who were treated with expansive open-door laminoplasty from February 2012 to January 2015. The operational level ranged from C3-C7 in all patients. The laminae open angles at the C4, C5, and C6 levels were measured 1 week postoperative. The mean value was taken for statistical analysis. The patients were divided into 2 groups, group A  and group B . C2-C7 Cobb angle, range of cervical motion (ROM), Japanese Orthopedic Association (JOA) score, and visual analog scale (VAS) score for axial pain were compared between the 2 groups.P < .05). Preoperative and postoperative C2-C7 Cobb angle and ROM comparisons were significantly different (P < .05) in both groups. There were no significant difference for other clinical and radiography parameters between the groups (P > .05). At 2 weeks and 6 months after surgery, there was significant difference in axial symptoms between the 2 groups (P < .05). At final follow-up, the difference between the 2 groups was not statistically significant (P > .05).All patients completed at least 2-year follow-up. Both groups gained significant JOA improvement postoperatively (In different angles of the lamina open-door, incidence of axial symptoms has statistically difference between the 2 groups. When the lamina open-door angles are <40°, there are not only ensure adequate spinal cord decompression but reduces the incidence of early and midterm postoperative axial pain. Some researchers have reported that EOLP is a reliable technique and results in satisfactory clinical results.–5 However, there are still some inevitable complications after laminoplasty, including postoperative axial pain, lamina reclosure and C5 root palsy. In particular, postoperative persistent axial pain could trigger off patient's dissatisfaction after surgery, even in patients with excellent neurologic recovery.Expansive open-door laminoplasty (EOLP), designed by Hirabayashi et al,–8 Some studies noted that the lamina open angle should be small, excessive opening angle did not reduce the incidence of reclosure but increase occurrence of complications.–13 However, they did not continue to explore the relationship between the opening angle and axial symptoms. The objective of the present study was to explore the effect of different laminae open angles on postoperative axial symptoms and to discuss the possible mechanism of the impact of different open angles on axial symptoms.In recent years, spinal surgeons have proposed some methods to reduce the incidence of axial symptoms, such as preserving C7 spinous process, reconstructing posterior extensor muscles, and early removal of the cervical collar.2As this was a retrospective study using data routinely collected, according to a waiver issued by the ethics committee of Tianjin Union Medical Center, specific ethics approval for this study was not required.2.1We retrospectively reviewed the data of 124 patients with multilevel cervical compression myelopathy who were treated with EOLP from February 2012 to January 2015. There were 76 men and 48 women. The age at surgery ranged from 39 to 80 years, with an average age of 63 years. The diagnosis of cervical myelopathy was confirmed both by a thorough neurologic examination and by the magnetic resonance imaging findings of spinal cord compression. The primary diseases included cervical spondylotic myelopathy (CSM) in 101 cases and ossification of the posterior longitudinal ligament (OPLL) in 23 cases. In these cases, combined radiculopathy and foraminal stenosis were included. Patients with rheumatoid arthritis, traumatic spinal cord injury, cerebral palsy, and history of cervical surgery were excluded. The operation level ranged from C3-C7 in all patients. The mean follow-up duration was 26.7 months (range 24–30 months). The operative procedure was expansive open-door using nonabsorbable sutures to secure the opened laminae.In this study, laminae open angles were measured at the C4, C5, and C6 levels after laminoplasty by picture archiving and communication system software, the mean value was taken for statistical analysis. The average lamina open angle was 40.2° ± 11.3°, ranged from 20° to 69°in these cases. The patients were divided into 2 groups, group A  and group B  according to different opening angles after surgery  = (Postoperative JOA score – Preoperative JOA score)/(17 – Preoperative JOA score) × 100%. VAS score for axial pain was recorded at preoperative 1 week, postoperative 2 weeks, 6 months, and final follow-up, respectively. The patients who experienced complications including infection, cerebrospinal fluid leakage, and lamina reclosure were recorded.2.4 The final measurement of the lamina opening angle = postoperative angle (b)-preoperative angle (a), taking the average value for statistical analysis . Continuous variables were presented as mean ± standard deviation. Independent-sample 33.1P > .05). There were no significant differences between the 2 groups in sex, age, diagnosis, blood loss, operation time, duration of disease, and duration of follow-up (P > .05). The difference for preoperative neck pain was not significant between the 2 groups (P = .83)  between the 2 groups. C2-C7 Cobb angle and ROM were significantly different before and after surgery for both groups. The radiography data are summarized in Table The cervical CT was reviewed a week after surgery, and the laminae angles were measured. Group A included 71 patients (open angle < 40°), and group B had a total of 53 cases (open angle ≥ 40°) . At 2 weeks after operation, there were 50 patients  complained of severe postoperative neck pain. The mean VAS was 2.4 ± 1.8 in group A and 3.1 ± 1.7 in the B group, the difference was significant (P = .03). At 6 months, there were 10 patients in group A  and 17 patients in group B , which was statistically significant (P = .03). At final follow-up, there were 3 patients in the group A  and 5 patients in the group B , the difference between the 2 groups was not statistically significant (P = .24). The axial symptoms gradually decreased in all patients during the experimental period. However, early and midterm axial pain were predominantly observed in group B (the large lamina open angle), late axial pain was no significant difference between the 2 groups. The data are summarized in Table The 10-point VAS score  for axial symptoms were examined at preoperative 1 week and postoperative 2 weeks, 6 months, and final follow-up. Preoperatively, 16 patients complained of significant neck pain in group A and 13 patients in group B. The mean preoperative neck pain VAS was 2.5 ± 2.1 and 2.4 ± 1.8 in both groups, respectively, and there was no significant difference between the 2 groups (4–19Axial symptoms have been recognized as one of the most serious complications after posterior decompression surgery. Several possible sources have been proposed, including posterior skeletal structures destruction, facet joint damage, nerve root injury, extensor muscles atrophy, resection of C2 or C7 spinous processes, and range of cervical motion decrease. noted that increase in opening angle to 40° or more did not reduce the incidence of restenosis and might be a risk factor for nerve root palsy after laminoplasty. A recent retrospective study indicated that lamina open angle of 53.5° can be an appropriate threshold between clinically adequate decompression and increasing risk of C5 palsy. Although their methods of measurement were different from ours, their studies showed that excessive opening angle could not acquire satisfactory clinical results. In a recent retrospective study, Zhang et al discussed the relationship between clinical results of EOLP with different open angles and recommended the lamina open angle should be maintained at about 30°. In that research, there was no further discussion of the effect of different lamina open angle on the incidence of midterm and late axial neck pain. In this study, when opening angles are <40°, the surgery can not only ensure adequate spinal cord decompression but minimize the impact on posterior organizational structure, thereby reducing the incidence of axial symptoms.It is still unclear as to what is the appropriate open angle to obtain adequate decompression of the spinal cord. Wide opening angle is expected to reduce the risk of reclosure by changing the direction and strength of muscles attached to the lamina. However, excessive opening angle of the lamina may increase the incidence of complications. Lee et al1.In single open-door laminoplasty, the spinous processes were deviated from the normal position, the large open angle correlates with more worse unsymmetry of posterior skeletal structure, resulting in obvious axial symptoms.2.In single open–door laminoplasty, paravertebral muscles were detached from laminae, leading to atrophy of the muscles, the influence on extensor muscle strength was more prominent when lamina open angle is large.3.The tension of suture stay in the spinous process and the facet capsule is more obvious when open angle was large, damaging the facets and soft tissue and resulting in nonbacterial inflammation around facet joint capsule.4.Excessive opening angle cause the formation of more epidural scar tissues, compressing spinal nerve root.Our study showed that the incidence of axial pain in the large open-door group was higher than in the small open-door group. The possible reasons are as follows: noted that the biggest disadvantage of open-door laminoplasty was that the postoperative posterior skeletal structure of the cervical spine became unsymmetrical. In a prospective randomized clinical study, Okada et al considered that axial pain was improved in French-door laminoplasty but became worse in open-door laminoplasty, the result could be explained by the asymmetry of posterior structure after open-door laminoplasty. In a retrospective case–control study, Chen et al stated that the destruction of cervical posterior structures, such as the posterior muscles and bony structures might lead to axial symptoms. In our study, the large angle of opening caused more obvious asymmetry of the posterior vertebral column, leading to a higher incidence of axial symptoms.The asymmetry and damage of posterior vertebral column may be one of the causes of axial symptoms. Hirabayashi et al,25 Kotani et al emphasized that employing the deep extensor muscle-preserving approach might be effective in reducing axial pain when compared to conventional open-door laminoplasty. Fujibayashi et al found that axial symptoms and muscle strength reduction were significantly correlated and reduction in muscle strength might easily result in the occurrence of axial pain. Some researchers hold opposite views, Hosono et al revealed that C7 and not the deep extensor muscles was significantly related to axial pain, extensor muscle detachment from the lamina may cause mild pain early after surgery but not result in significant chronic axial pain. Riew et al indicate that preservation of sub-axial deep extensor muscles plays no significant role in reducing axial neck pain after cervical laminoplasty. In this study, early and midterm axial pain between the 2 groups was statistically significant, late axial pain was no significant, the main reason might be a temporary reduction in muscle strength occurred during the early postoperative period. The muscles strength gradually recovers after 1 year. As showed in the study, Fujibayashi et al noted that muscle strength recovered by 3 months and had increased to 120% of the preoperative value by 12 months after the operation in most patients.The relationship of cervical posterior extensor muscles with persistent axial pain following laminoplasty is still controversial. In traditional open-door laminoplasty, the extensor muscles are detached from the spinous process and their insertions are damaged, leading to dystrophy and atrophy of the muscles. Some surgeons have considered the posterior muscle atrophy a source of axial pain, they found that less invasive to the posterior extensor muscles of the cervical spine was an effective procedure for preventing postoperative persisting axial pain. reviewed literatures about classic laiminoplasty procedure and concluded that postoperative axial symptoms might be related to dissection around the facets and soft tissue. Chen et al indicated that the conventional procedure made a retention suture on the facet capsule and damaged the capsule, increasing the incidence of axial symptoms. Cohen et al reported that capsule stretch activates nociceptors could be a possible cause of persistent neck pain. The neurophysiologic studies considered injured facet-joint capsules as a source of the cervical spinal pain. They noted that inflammation of the facet joints leads to decreased thresholds of capsule receptors, which may then lead to persistent pain. In this study, the open-door was kept open by placing a suture through the facet capsule on the hinge side and through the spinous processes. When lamina open angle was large, the tension of suture in the spinous process and the facet capsule was more obvious, resulting in axial neck pain.Facet capsule suture and stretch are discussed as another important factor related to axial symptoms. Wang et al concluded that the modified open-door laminoplasty using titanium miniplate was effective in preventing the incidence of axial neck pain. The possible cause was that scar tissue was prevented outside of the spinal canal by the miniplate.Stimulation and injury of the cervical nerve root branches may be associated with the occurrence of axial symptoms. Excessive opening angle created large epidural space, resulting in the formation of more epidural scar tissue to compress the nerve root. Chen et al found that preoperative higher axial neck pain intensity was one of the independent predictors of postoperative moderate-to-severe axial neck pain at the 2-year follow-up. Ohnari et al got another result that the preoperative axial symptoms might be not related to postoperative axial symptoms. The present study showed no significant correlation between preoperative and postoperative axial symptoms.Preoperative neck pain might be linked to postoperative axial symptoms. However, this problem was still an argued item. Kimura et al,19 The reasons may be as follows: early removal of the cervical collar and early active cervical muscle exercises might increase local blood circulation, accelerate the repair of soft tissue and prevent muscle atrophy, thereby reducing the incidence of axial symptoms.In the present study, our patients wore a hard cervical collar for 3 weeks followed by active isometric exercise of cervical muscle. Prolonged external fixation might be more helpful in promoting hinge lateral bone healing; however, several studies have indicated that the duration of brace use is related to postoperative axial pain.There were several limitations in the present study. First, muscle strength was not measured before and after cervical surgery using specific measurement device. Additional study is needed to observe the relationship between changes in muscle strength and different laminae open angles. Second, the sample size of this study is small and more clinical studies are needed to explore the most appropriate open angles.In conclusion, there is no significant difference in neurologic recovery rate between the different lamina opening angles. Incidence of axial symptoms has a statistically significant difference between the 2 groups. When laminae open-door angles are <40°, it not only ensures adequate spinal cord decompression but reduces the incidence of early and midterm postoperative axial pain.The authors thank all the people who give the help for this study.Conceptualization: Jizhou Wang, Tianwei Sun, Xiaoqi He.Data curation: Jizhou Wang, Tianwei Sun, Xiaoqi He.Formal analysis: Jizhou Wang, Tianwei Sun.Investigation: Jizhou Wang, Xiaoqi He.Methodology: Jizhou Wang, Xiaoqi He.Project administration: Jizhou Wang, Tianwei Sun,Resources: Tianwei SunSoftware: Xiaoqi He.Supervision: Jizhou Wang, TianweiValidation: Jizhou Wang, Tianwei Sun, Xiaoqi He.Writing – original draft: Jizhou Wang, Tianwei Sun, Xiaoqi He.Writing – review & editing: Jizhou Wang, Tianwei Sun


Non-invasive vagus nerve stimulation (nVNS) has been shown to be practical, safe, and well tolerated for treating primary headache disorders. The recent multicenter, randomized, double-blind, sham-controlled PRESTO trial provided Class I evidence that for patients with episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. We report additional pre-defined secondary and other end points from PRESTO that demonstrate the consistency and durability of nVNS efficacy across a broad range of outcomes.n = 122) or a sham device (n = 126) during a double-blind period lasting 4 weeks (or until the patient had treated 5 attacks). All patients received nVNS therapy during the subsequent 4-week/5-attack open-label period.After a 4-week observation period, 248 patients with episodic migraine with/without aura were randomly assigned to acute treatment of migraine attacks with nVNS (n = 120) had a significantly greater percentage of attacks treated during the double-blind period that were pain-free at 60 (P = 0.005) and 120 min (P = 0.026) than the sham group (n = 123) did. Similar results were seen for attacks with pain relief at 60 (P = 0.025) and 120 min (P = 0.018). For the first attack and all attacks, the nVNS group had significantly greater decreases (vs sham) in pain score from baseline to 60 min (P = 0.029); the decrease was also significantly greater for nVNS at 120 min for the first attack (P = 0.011). Results during the open-label period were consistent with those of the nVNS group during the double-blind period. The incidence of adverse events (AEs) and adverse device effects was low across all study periods, and no serious AEs occurred.The intent-to-treat population consisted of 243 patients. The nVNS group (These results further demonstrate that nVNS is an effective and reliable acute treatment for multiple migraine attacks, which can be used safely while preserving the patient’s option to use traditional acute medications as rescue therapy, possibly decreasing the risk of medication overuse. Together with its practicality and optimal tolerability profile, these findings suggest nVNS has value as a front-line option for acute treatment of migraine.NCT02686034.ClinicalTrials.gov identifier:  Standard pharmacologic agents for the acute treatment of migraine can be limited by side effects, inconsistent efficacy, contraindications, risk of drug interactions, and their potential contribution to migraine chronification and medication overuse headache –5. OpioiNon-invasive vagus nerve stimulation  demonstrated efficacy in studies of acute migraine treatment and has a strong safety and tolerability profile –15. The Complete details of the methodology of the multicenter, randomized, double-blind, sham-controlled PRESTO trial have been reported previously . The stuStudy patients were 18 to 75 years of age, had a previous diagnosis of migraine with or without aura according to the International Classification of Headache Disorders, 3rd edition (beta version) criteria , were < Patients were randomly assigned (1:1) to receive nVNS or sham  Fig.  and recoPain-free was defined as a score of 0 on the 4-point headache pain scale (with 0 indicating no pain and 3 indicating severe pain), and pain relief was defined as a score of 0 or 1 (both without use of rescue medication before 120 min) in a subject with pain of at least moderate severity at baseline. Attacks with mild pain  at both baseline and the subsequent time point of interest were considered treatment failures. These definitions were used in assessment of the following end points:Percentages of all treated attacks that achieved pain freedom and pain relief at 30, 60, and 120 min for the double-blind period and at 120 min for the open-label period;Mean change in pain score from baseline to 30, 60, and 120 min for the first attack and for all attacks in the double-blind and open-label periods;Number of acute medications used per migraine attack during the observational, double-blind, and open-label periods;ustained treatment response  rates for the first attack and all attacks for the double-blind and open-label periods;SIncidence of adverse events (AEs) and adverse device effects (ADEs).Here, we present clinically relevant secondary and other end points not included in the original PRESTO publication to provide a more comprehensive depiction of the data set. intent-to-treat (ITT) population, defined as all randomly assigned patients who treated at least 1 migraine attack in the double-blind period. Descriptive statistics were used to summarize continuous variables  and categorical variables . Generalized linear mixed effects regression models were used to estimate the proportion of all attacks that were pain-free or had pain relief for the nVNS and sham groups, allowing for both subject-specific and population-averaged inferences in non-normally distributed data; P values were from resulting F tests. Mean change from baseline pain score was compared between treatment groups via 2-sample t tests for the first attack and via linear mixed effects regression models. Poisson regression was used to compare medication use per attack between treatment groups. For sustained treatment response (pain-free and pain relief), the nVNS and sham groups were compared via the chi-square test or Fisher exact test, as appropriate, for the first attack and via linear mixed effects regression models for all attacks. All data were analyzed using SAS®9.4 . Two-sided P values < 0.05 were considered statistically significant.All efficacy end points were evaluated using the n = 120; sham, n = 123). Two hundred thirty-nine patients entered the open-label period ; among these, 238 patients (> 99%) completed this period (1 patient was lost to follow-up), with 220 (92%) treating at least 1 attack during the period. One patient who treated at least 1 attack in and completed the open-label period was not part of the ITT population. Table Complete descriptions of patient disposition, demographics, and baseline characteristics in PRESTO are included in the original study publication . The ITTP < 0.05 for both time points)  and 35.2% for the nVNS group and 25.4% for the sham group at 120 min (P = 0.018).In the nVNS group, the percentage of all attacks that were pain-free at 60 min (16.3%) and 120 min (22.9%) was significantly greater than in the sham group  Fig. . Similarts) Fig. , which wP = 0.029) and 120 min . For all attacks  but not at 120 min .For the first attack Fig. , the nVNcks Fig. , the meaP = 0.055).During the observational (run-in) period, study patients used a mean of 0.86 acute medications per attack. Acute medication use decreased during the double-blind period to 0.45 medications per attack in the nVNS group and 0.55 medications per attack in the sham group (Sustained pain-free and pain relief response rates were high in both the nVNS and sham groups at 24 h (≥75%) and 48 h (≥58%) for both the first attack and all attacks  or had pain relief (38.1%) at 120 min during the open-label period were similar to those of the nVNS group during the double-blind period  and for all attacks (60 min). Among nVNS-treated attacks that were pain-free at 120 min, > 75% had a sustained response at 24 h. Ninety-eight percent of patients in the ITT population completed the open-label period, suggesting that the benefit from nVNS was maintained and that nVNS is a durable acute therapy. The results for the total population during the open-label period were generally similar to those seen for the nVNS group during the double-blind period. Throughout the study, the incidence of AEs and ADEs was low, and no serious AEs were reported.The findings from PRESTO are consistent with those from other clinical studies of acute nVNS use in migraine , 13. TheThe high rates of sustained 24-h pain-free response to nVNS seen in PRESTO (> 75%) stand in contrast to the lower rates reported for oral triptans 10%–30%) and single-pulse transcranial magnetic stimulation (29%) %–30% and. The proTogether with findings from multiple previous studies , 24–26, This study has a number of limitations. The selection of an appropriate sham device in neuromodulation studies is challenging. In accordance with previous recommendations to ensure maintenance of the study blind , the shaDuring both the double-blind and open-label periods, the mean number of acute medications used per migraine attack was substantially lower than that seen during the observational period. Such a decrease in medication use could be interpreted as evidence of treatment efficacy; however, these results must be interpreted with caution, as patients were encouraged to refrain from using acute medications for 120 min after stimulation with the study device. This study limitation most likely contributed to decreases in acute medication use in both the nVNS and sham groups during the double-blind period and may partially explain the lack of significance between treatment groups for this end point.These results from clinically relevant secondary and other end points of the PRESTO study demonstrate the efficacy and reliability of nVNS for the acute treatment of migraine. nVNS provided dependable efficacy for the successful treatment of multiple attacks and can be used safely while preserving a patient’s option to use additional acute medications as rescue therapy, thus potentially decreasing the risk of medication overuse. Together, these findings highlight the flexibility and practicality of nVNS as a front-line option for acute migraine attacks.


To examine the results of an anular closure device for prevention of lumbar disc reherniation in daily routine practice.Fifty patients with large anular defects were treated with limited discectomy and a bone‐anchored anular closure device. The device physically occludes the defect in the anulus fibrosus and is intended for prevention of lumbar disc reherniation. Pain scores on a visual analogue scale, back function on the Oswestry Disability Index, and neurological status were noted. Symptomatic reherniation and reoperation rates were assessed at each follow‐up. Surgical findings and complications, device‐related and/or procedure‐related, were recorded. Follow‐up was 6, 12, 26, and 52 weeks.P < 0.001), leg pain decreased from 71 to 4 (P < 0.001), and the Oswestry Disability Index decreased from 46 to 5 (P < 0.001). Among 15 patients with preoperative neurological deficits, improvements in neurological function were noted in 14 (93%). There were no serious device‐related complications.Mean anular defect height/width was 4.6 mm/10.1 mm. The overall symptomatic reherniation and reoperation rate was 2%. During the 1‐year follow‐up period, mean back pain decreased from 43 to 8 (The presented study shows promising early results in using the anular closure device. The procedure is safe with significantly fewer reherniations than for patients with large anular defects without anular closure. Further studies with longer follow‐up periods are warranted to prove these findings for long‐term outcomes. Lumbar discectomy is one of the most frequently performed spine surgeries. Surgical treatment shows quicker improvement in pain compared to conservative treatmentvs 2%–10%). Similar findings were reported in a 2015 meta‐analysis by Ran et al.et al. pointed out that limited discectomy is associated with less back pain than radical discectomy  but higher reherniation rates (1.0%–21.2% vs 0%–10.5%).Overall, discectomy results are good; however, 10%–30% of all surgically‐treated patients with lumbar disc herniations are unsatisfiedet al.et al.5/S1 with anular defects ≥6 mm had a reherniation rate of 18%. The study of McGirt et al.In 2003, Carragee Summing up the results of these studies, reherniation is a problem that is disproportionately focused on a smaller subset of patients with large anular defects. In addition, limited discectomy is a favorable technique to reduce the potential for subsequent back pain but bears a high risk of reherniation in this patient groupTo solve this dilemma, different techniques and implants have been investigated to close the anular defect after discectomy with the hope of reducing the reherniation rate without increasing the risk of more back pain resulting from aggressive nucleus removal. An anular closure device (ACD) was developed consisting of multiple layers of a polymer fabric and a titanium anchor . The dense fabric occludes the anular defect while the anchor, which is implanted into the vertebral body, ensures a stable position for the implant Fig. . For theEligible patients were at least 18 years of age with a disc height ≥5 mm on preoperative MRI, and a large anular defect measuring ≥4 mm in height and ≥6 mm in width. Patients with significant osteoporosis, infections, tumors, or spondylolisthesis >1 were excluded.For this study, 50 consecutive patients with lumbar disc herniations treated with limited discectomy and anular closure were enrolled prospectively. All patients provided informed consent for treatment with the ACD. None of the included patients was excluded after surgery. Basic demographic data and the following data were recorded preoperatively: length of conservative care, prior lumbar surgery, neurological status, body mass index, back and leg pain scores , quality of life  and disc height measured on MRI.All operations were performed under standard microsurgical conditions. The first step of the procedure involved limited discectomy according to SpenglerSurgical data included defect height and width, amount of nucleus removal (measured in mL), surgical time, and surgical complications (associated and not associated with the implant).Patients were seen postoperatively at 6, 12, 26, and 52 weeks. Key outcome measures were back pain, leg pain, ODI, neurological status, and complications, including clinical signs of reherniation.Back pain and leg pain severity were each assessed on a 0–100 VAS, where higher scores represented more pain. ODI was measured on a 0–100 scale, where higher scores represented greater disability.Neurological status was assessed by physical examination and neurological deterioration was defined by a decrease in neurological status relative to the previous follow‐up visit.All complications reported by a patient at each follow‐up visit, regardless of the relationship to the device or procedure, were recorded. The wound/scar was inspected at each visit to identify possible wound complications. Symptomatic reherniation was suspected if a patient presented with recurring radicular symptoms and a positive straight leg raise. In patients with suspected reherniation, X‐ray and MRI were performed to confirm or exclude the diagnosis. Patients with a worsening of VAS scores or ODI scores also underwent x‐ray and MRI to identify possible causes of clinical deterioration.t‐test. Statistical significance was set at 0.05 and all tests were two‐sided. Data were analyzed using SPSS Statistics version 25 .Baseline patient characteristics were reported as mean and standard deviation for continuous variables and count (percent) for categorical variables. Changes in back pain, leg pain, and ODI from baseline to 1 year were analyzed with a paired samples 2. Three of the patients presented with a reherniation after primary surgery without an implant in another hospital and were treated with an ACD. One patient had a two‐level disc hernia and, therefore, overall, 51 segments were operated on in the present study. The most affected levels were L4/5 (26 cases) and L5/S1 (19 cases). Mean preoperative leg and back pain scores  were 70.5 ± 33.2 and 43.4 ± 24.3, respectively. Mean ODI was 46.2/100 ± 16.3, and the disc height of the treated level was 6.3 mm . Mean body mass index of the 50 patients was 28.0 kg/m2 .Patients were seen at 6 (45 patients), 12 (47 patients), 26 (46 patients), and 52 weeks (45 patients) after surgery. Leg pain  was 70.5 ± 24.5 preoperatively and decreased to 8.0 ± 14.8, 9.5 ± 21.1, 7.3 ± 16.0, and 4.4 ± 14.8 after 6, 12, 26, and 52 weeks, respectively. Back pain was 43.4 ± 33.5 preoperatively and decreased to 13.5 ± 19.0, 13.3 ± 22.1, 12.1 ± 20.8, and 8.0 ± 18.9 after 6, 12, 26, and 52 weeks, respectively.P < 0.0001) at all follow‐up time points . Pain scores and ODI reduced significantly  cases (in 1 of these patients there was a slight worsening of the long toe extensor while the foot elevator improved postoperatively). In 1 patient there was no change in the preoperative motor deficit.There were no wound infections. We had 1 patient with reherniation (2.0%) 6 weeks after primary surgery who underwent reoperation. After reoperation the recovery course was uneventful. Another patient had a second surgery 8 months after the first surgery due to dislocation of the implant to dorsal. The reason was an improper first implantation . During follow‐up none of the other patients had a reoperation.The presented study consists of typical “real‐life” discectomy patients with a high rate of reherniation due to the large anular defect. The use of an anular closure device in these patients was safe and appears to substantially reduce the risk of recurrent herniation.Six months after surgery VAS leg pain was reduced significantly, from 70.5 preoperatively to 4.4, and VAS back pain was reduced from 43.4 to 8.0. Lumbar discectomy studies showed consistent findings at 6 months: PeulThe ODI is one of the instruments most frequently used to describe function and disability in patients requiring spine surgery. Before surgery, the presented patient population had a mean ODI of 46.2, which translates to significant disability in this study cohort, reducing to 4.7 at 12 months. In comparable studies, patients had similar results. LequinNeurologically, 15 of our 50 patients had a motor deficit due to the disc herniation before surgery; 14 patients (93.3%) improved postoperatively  and no change was seen in 1 patient. In Yorimitsu'sThe excellent meta‐analysis of ShriverDisc reherniations are both a clinical and a socioeconomic problemet al.12 Only one of them (2.0%) had a reherniation during the follow‐up at 12 months. ChengCarragee The presented study reveals that the use of an ACD in patients with large anular defects appears to reduce the risk of a reherniation significantly. Nevertheless, the study has some limitations which should be taken into account. The follow‐up period of 12 months is not long and the sample size (50 patients) is small. Furthermore, there is no control group and no routine imaging follow‐up was performed. Therefore, no data can be given concerning cost effectiveness relative to discectomy alone or to the frequency of mesh or implant migration. Finally, because eligible patients had large anular defects following lumbar discectomy, no conclusions can be drawn from this study on the efficacy of anular closure in small anular defects.Following lumbar disc surgery, reherniation rates are high in patients with large anular defects. While an anular closure device has been studied in a randomized superiority study, little has been reported about this kind of implant utilized within routine daily practice. The presented study demonstrates that the use of an anular closure device in this setting is safe with reduction of reherniation without higher complication rates or identified safety concerns. Further studies will be meaningful to prove these findings with long‐term follow‐up.


The use of epidural analgesia (EA) in pancreatic surgery remains under debate. This study compares patients treated with EA versus non-EA after open pancreatectomy in a tertiary referral center.All patients undergoing open pancreatectomy from 2013 to 2017 were retrospectively reviewed. (Non-)EA was terminated on postoperative day (POD) 3 or earlier if required.P < 0.001) and POD 1 (2.00 (0.50–3.41) versus 3.00 (2.00–3.80), P = 0.001), though significantly higher pain scores on POD 3 (3.00 (2.00–4.00) versus 2.33 (1.50–4.00), P < 0.001) and POD 4 (2.50 (1.50–3.67) versus 2.00 (0.50–3.00), P = 0.007). EA patients required more vasoactive medication perioperatively and had higher cumulative fluid balances on POD 1–3. Postoperative complications were similar between groups.In total, 190 (72.5%) patients received EA and 72 (27.5%) patients received non-EA (mostly intravenous morphine). EA was terminated prematurely in 32.6% of patients and non-EA in 10.5% of patients. Compared with non-EA patients, EA patients had significantly lower pain scores on POD 0 (1.10 (0–3.00) versus 3.00 (1.67–5.00), In our cohort, patients with EA experienced significantly lower pain scores in the first PODs compared with non-EA, yet higher pain scores after EA had been terminated. Although EA patients required more vasoactive medication and fluid therapy, the complication rate was similar.The online version of this article (10.1007/s11605-019-04136-w) contains supplementary material, which is available to authorized users. Analgesic outcomes are structurally registered in the medical records since June 2013, therefore this period was selected. Only patients undergoing open pancreatectomy were included .Two authors (J.V.G. and D.E.F.S.) performed retrospective data extraction from medical records according to a predefined case report form. Data up to 90 days after surgery or 30 days after discharge were extracted. Extracted data were randomly reviewed by two authors  for quality control. Variables of interest included (1) patient-related variables: patient characteristics, history of chronic pancreatitis, American Society of Anesthesiologists (ASA)-score, preoperative drug use , underlying pathology; (2) anesthesia-related variables: type and duration of anesthesia, type and duration of postoperative analgesic treatment, conversion , reason for conversion, type of analgesia following EA or ivPCAM, pain scores, use and duration of vasoactive support, cumulative fluid balances; (3) surgery-related variables: type and duration of surgery, blood loss; (4) postoperative variables: duration of admission to the medium care unit (MCU) or ICU, complications related to analgesia treatment, postoperative complications, length of hospital stay, discharge destination, readmission.13 Opioids not part of standard EA or ivPCAM infusion , subcutaneous (SC), or oral (PO)) were considered “supplemental opioids”. The reason for EA termination was classified as “hemodynamic instability” in case perioperative hemodynamic parameters did not improve despite vasoactive medication and fluid therapy. Postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, and chyle leak were all classified by the International Study Group of Pancreatic Surgery definitions.18 For all these complications, grade B and grade C were considered as clinically relevant. The following complications of analgesia were investigated: opioid-induced respiratory depression, infection of puncture sites, postdural puncture headache, and subdural hematoma. The Clavien-Dindo Classification was used to classify overall postoperative complications per patient.19The EA group consisted of patients with an epidural catheter during surgery and the N-EA group consisted of patients with all types of analgesia other than EA. The day of surgery was considered as POD 0. Pain scores were measured on an 11-point numerical rating scale (NRS) to assess pain intensity: ranging from 0 (no pain) to 10 (most extreme pain imaginable). A NRS > 4 is an indicator for adjustment of the analgesic regimen and was therefore the cutoff value between acceptable and non-acceptable pain and used for analyses of patients who reported unacceptable pain during PODs 0–10.All patients were preoperatively assessed by an anesthesiologist. Based on the preoperative conditions of the patient, type of surgery, and preferences of both patient and physicians (anesthesiologist and surgeon), a shared decision was made regarding the type of analgesic treatment . None of the involved anesthesiologists and surgeons refused to use either EA or N-EA.Perioperative hemodynamic therapy was goal-directed according to local protocol: focused on maintaining a mean arterial pressure > 55 mmHg and a urinary output of > 0.5 mL/kg/h and preventing excessive fluid administration.EA and N-EA treatments were applied according to local protocol. In the case of EA, the epidural catheter was inserted preoperatively at level Th6-Th10. EA patients received 0.2% ropivacaine combined with 0.75 μg/mL sufentanil. The background continuous infusion rate was 4–8 mL/h. If needed, patients could manually administer an additional bolus . In addition, patients received 1 g acetaminophen (paracetamol) 4 times daily. Because of sterility considerations, EA was terminated 72 h after surgery . Thereafter, patients received a combination of acetaminophen and nurse-administered IM/SC/PO opioids (in absence of contraindications) depending on NRS scores.20 was responsible for analgesic management for the duration of EA or ivPCAM. The Acute Pain Service visited the patients twice daily to evaluate and modify analgesic management if needed. Together with the nursing staff, they were responsible for measuring pain scores (on the NRS) at least three times a day according to national protocol.21Patients with N-EA generally received intravenous (IV) morphine bolus doses postoperatively to reduce pain scores ≤ 4, followed by ivPCAM. IvPCAM included a background infusion rate of 0.5 mg/h. In addition, the patients could administer a 1 mg bolus at a 5 min interval with a maximum dosage of 28 mg per 4 h. Furthermore, patients received 1 g acetaminophen 4 times daily. IvPCAM was terminated 72 h after surgery . Thereafter, patients continued to receive acetaminophen now combined with nurse-administered IM/SC/PO opioids (in absence of contraindications) depending on pain scores. The Acute Pain ServiceThe primary outcome of this study was the mean pain scores and percentage of patients who reported unacceptable pain per POD. The secondary outcomes were the details of analgesic treatment , perioperative hemodynamics , and the postoperative outcomes .t tests or Mann-Whitney U tests, depending on their distribution. Categorical variables are presented as numbers (percentages) and compared by chi-square or Fisher’s exact tests. For analyses of pain scores, we calculated the mean NRS per patient per POD and identified patients who reported unacceptable pain (pain score > 4) at least once per POD. Because the mean pain scores are not normally distributed, values are presented as median (IQR). Cumulative fluid balances were calculated per patient by adding up fluid balances of preceding days and the POD of interest. Main analyses were based on the comparison of patients with EA versus patients with N-EA. Subgroup analyses were performed with patients who completed the first three PODs with their initial analgesic technique . For statistical analyses, SPSS Inc. for Windows (version 23.0) was used. P values < 0.05 were considered significant.Continuous variables are presented as mean (standard deviation) or median (interquartile range) and compared by unpaired N = 28), preoperative failure of placement (N = 20), physicians’ preference (N = 15), and patients’ preference (N = 9). Type of resection did not differ between groups (P = 0.161).In total, the study cohort consisted of 262 patients: 190 (72.5%) patients in the EA group and 72 (27.5%) in the N-EA group (Table N = 25), hemodynamic instability (N = 20), catheter dislocation (N = 11), and without reported problems (N = 6). In the patients with prematurely terminated EA, 41 patients received ivPCAM following EA . In addition, four patients received ivPCAM after termination of EA according to protocol. IvPCAM was terminated prematurely in 16 (10.5%) patients, due to inadequate pain control (N = 2) and without reported problems (N = 14). All ivPCAM patients received nurse-administered IM/SC/PO opioids after termination of ivPCAM.Initial analgesia was terminated on POD 3 without reported problems (according to protocol) in 119 (62.6%) patients with EA and 21 (32.8%) patients with ivPCAM  versus 3.00 (1.67–5.00)) and POD 1 (2.00 (0.50–3.41) versus 3.00 (2.00–3.80)), whereas they experienced statistically significantly higher mean pain scores on POD 3 (3.00 (2.00–4.00) versus 2.33 (1.50–4.00)) and POD 4 (2.50 (1.50–3.67) versus 2.00 (0.50–3.00); Fig. P < 0.001 Fig. P = 0.012). Conversely, the EA-group reported unacceptable pain significantly more often on POD 3  and POD 4 . From POD 5 forward there were no significant differences between groups.The EA group reported unacceptable pain (pain scores > 4) significantly less often on POD 0 , POD 1 (N = 154) and POD 2 (N = 134) experienced significantly lower mean pain scores and less unacceptable pain per POD compared to patients with N-EA . From POD 4 forward, there were no significant differences between groups.Both groups had a similar cumulative fluid balance on POD 0 Fig. . While oP = 0.335). In all deceased patients, the cause was not related to the type of analgesia. The length of hospital stay did not differ between the two groups.There were no differences between groups regarding postoperative complications and Clavien-Dindo classification Table . In the 23 A recent randomized controlled trial in patients undergoing major HPB surgery showed improved pain control and similar postoperative outcomes between the EA and ivPCAM group, although only 3% of included patients underwent pancreatectomy.24 Therefore, our large cohort study of solely patients undergoing pancreatectomy provides insight into the effects of analgesic technique. The forthcoming results of a randomized controlled trial comparing EA versus ivPCAM in patients undergoing PD could clarify the influence of analgesic technique on postoperative outcomes.25This study showed EA was used in 72.5% of patients undergoing open pancreatectomy. There were several important outcomes of the comparison between EA and N-EA patients: (1) initial analgesia was prematurely converted to another form of analgesia in 32.6% of EA patients versus 10.5% of N-EA patients; (2) EA patients had lower mean pain scores and fewer reported unacceptable pain on PODs 0–1. However, termination of EA led to higher mean pain scores and more patients reported unacceptable pain on POD 3–4, which led to the need for the liberal administration of supplemental opioids; (3) the EA group received more vasoactive medication perioperatively and also cumulative fluid balances were significantly higher on PODs 1–3; (4) postoperative complications and length of hospital stay were similar between both groups. Previous studies comparing EA with N-EA reported mixed results regarding pain scores and postoperative complications in relatively small cohorts of patients undergoing pancreatoduodenectomy (PD) and major hepatopancreatobiliary (HPB) surgery.26 Unlike our study, these studies did not report results after termination of EA. Therefore, it is unclear whether extending the EA phase after POD 3  would lead to lower pain scores and less use of opioids. Moreover, previous studies and our study showed the association between EA and perioperative hemodynamic instability, leading to early termination in 7–41% of EA (10.5% in our study).27 The higher cumulative fluid balances on PODs 1–3 in the EA group can be explained by the switch from vasoactive medication at the MC/IC to fluid therapy on the surgical ward to ensure adequate hemodynamic status. We hypothesize that excessive fluid therapy on the surgical ward is needed as long as the EA phase is prolonged. Therefore, we suggest not to extend the EA phase but to apply a multimodal analgesic regimen that covers the increase in pain scores upon EA termination.Possible solutions for the higher pain scores after termination of EA might be extending the EA phase or by a preemptive and more strict analgesic treatment (opioid or non-opioid) during the transition from EA to other analgesia. A prolonged EA phase (PODs 4–6) is already implemented in some other centers.28 A possible disadvantage is that the use of multiple wound catheters and pumps might impede early mobilization of the patient. Another study showed that pain scores after subcostal transversus abdominis plane catheters were comparable with EA in upper abdominal surgery.29 However, the catheters needed resiting in 45% of patients. Sublingual sufentanil tablets (SST) have been investigated and showed promising pain scores and safety parameters after open abdominal surgery.30 SST are rapidly absorbed, causing a minimal delay in pain relief, and because peak concentrations are low typical opioid side effect occur less frequent.31 The occurrence of other side effects  is comparable with other forms of opioid treatment.32 We started an investigator-initiated, multicenter, randomized controlled trial to compare SST and EA in patients undergoing PD .The high rate of premature termination of EA and worse pain control with ivPCAM implicate that a new alternative for postoperative analgesia is needed. Alternatives for postoperative analgesia have been investigated in previous studies. One study reported results of continuous wound infiltration compared to EA showing lower pain scores, less opioid side-effects, and less use of vasoactive medication after HPB surgery.Our study has several limitations. The registration of side effects  of analgesia was not reported in a standardized manner, which did not allow comparisons between groups. Our data indicate that the shared decision  to determine the postoperative analgesic technique is partly based on patient characteristics: the N-EA group had a higher ASA-score and more oral anticoagulant users. It may well be that comparison of outcomes between EA and N-EA patients are not just related to the analgesia technique but also to patient selection. We performed sensitivity analyses with patients undergoing PD (70.2% of patients) which showed similar results regarding all outcomes (data not shown). Nevertheless, in contrast to previous studies, this study presents a large cohort of open pancreatectomies with detailed data of analgesic management in the first 10 PODs and postoperative outcomes.In our cohort, patients receiving EA after open pancreatectomy had significantly lower pain scores in the first PODs compared with non-EA, yet higher pain scores after EA was terminated. Although EA patients required more vasoactive medication and fluid therapy, postoperative complications were similar between groups.Figure S1a) Median (IQR) of mean pain score per POD & (b) Patients with unaccpetable pain per POD. * Patients who reported a pain score >4 at least once per POD. (PDF 44.3 kb)Subgroup analysis of in situ analgesia: (


Children with central nervous system (CNS) malignancies often suffer from high symptom burden and risk of death. Pediatric palliative care is a medical specialty, provided by an interdisciplinary team, which focuses on enhancing quality of life and minimizing suffering for children with life-threatening or life-limiting disease, and their families. Primary palliative care skills, which include basic symptom management, facilitation of goals-of-care discussions, and transition to hospice, can and should be developed by all providers of neuro-oncology care. This chapter will review the fundamentals of providing primary pediatric palliative care. Neurological tumors comprise the second most common malignancy of children and adolescents, with an incidence of approximately 5000 children affected per year . In addiPalliative care for children is critical to providing optimal care for some of the most vulnerable patients ,4. ProviA critical aspect of primary palliative care is to assist with establishing goals-of-care with patients and families. Establishing goals first requires some determination of the patient’s and family’s values  and priorities; this is achieved across a series of conversations. Examples of common values and priorities include: Staying out of the hospital, controlling pain, spending time with loved ones, and achieving milestones, such as graduation ,12. ThesCommunicating well is important to patients, decreases uncertainty, and may improve hope and reduce decision regret . Most paPalliative care principles obligate providers and families to provide a developmentally appropriate explanation of disease and the burdens expected to the patient within the context of their values, culture, and preferences . EarlierA common decision put to families is whether and when to enroll in hospice. Hospice is a comprehensive home care program, with 24-hour, on-call nurse visits, home medication delivery, continuous 1:1 nursing if needed, and bereavement support. Eligibility for hospice only requires a reasonable possibility of death within six months; a do not resuscitation order is not required. Hospice utilizes a multidisciplinary approach focusing on comfort and quality of life. Advanced care planning is important for end-of-life care, including the patient’s/family’s preference for location of death. Unique to pediatrics is the concept of “concurrent care”, which allows children to “concurrently” receive both curative therapies and hospice .Another decision many families face is Phase I trial enrollment, which may provide families with a sense of hope, legacy, and dignity, despite a minimal likelihood of objective disease response. The burdens of the trial should be balanced with the family’s sense of benefit. Theoretically, enrollment on a clinical trial near end of life can complicate comfort-directed care plans because of study-related requirements, however, available data suggest that patients that enroll on Phase I trials have similar timing and frequencies of “do not resuscitate” (DNR) discussions, hospice enrollment, and established DNR orders to those that do not enroll on such trials .Since medical decisions in the palliative setting are value-based, conflicts may arise between family decision makers and medical teams regarding the goals of care and specifics of treatment. Conflict can be addressed at both a provider level and an institutional level. Providers of palliative care can mitigate disagreement by “shifting” to a more curious stance, in which “one focus[es] on learning more about the perspectives of both parties, exploring what may be a complex web of actions that contributed to the conflict.” . A simplThe symptoms experienced by children with brain tumors are varied and can be quite burdensome . The locExpert experience provides the bulk of treatment recommendations for oromotor dysfunction, which include speech therapy evaluation, thickening of feeds, and treatment with steroids to acutely reduce edema.Secretions often become difficult for patients to manage as they lose their oral motor proficiency and their alert mental status. The goal of treatment is to decrease respiratory distress, aesthetic distress of secretions, and to attain maximum patient comfort. Medicines used are muscarinic anticholinergics, such as glycopyrrolate, scopolamine, or atropine. Glycopyrrolate does not cross the blood-brain barrier and thus spares patients from central nervous system side effects. Scopolamine patches pose a convenient transdermal delivery system and are approved for patients greater than 45 kg. Atropine ophthalmic 1% solution can be given sublingually; 1 drop every 4 h providing 0.5 mg atropine per dose . Other tAs oromotor dysfunction progresses to dysphagia, nutrition and hydration often become concerns that need particular attention due to the fundamental nature of care through feeding. Nutrition and hydration should be framed by prognosis, risks (such as aspiration pneumonia), benefits , and focused on the experience of the patient. For those patients who can no longer feed by mouth yet express hunger or other symptoms due to a lack of intake, the benefits to intervening may outweigh the risks. Generally, if a child is likely to live longer than 90 days, it is reasonable to use more invasive solutions  if such procedures are aligned with family and patient values. If the prognosis is shorter, a nasogastric or nasojejunal feeding tube is more appropriate, with decreased risks, and foregoing feeds and fluids altogether is also an acceptable option for some. The burdens of feeds should not be forgotten; patients may feel discomfort from the feed itself, the tubes, or may have adverse responses to their change in appearance. When the primary goal is patient comfort, even when oral feeding poses an aspiration risk, it is reasonable to allow small amounts of intake for enjoyment. Conversely, when the primary goal is patient comfort, it is ethically sound to forego nutrition and hydration that are burdensome to the patient. Finally, offering hydration without nutrition or in the setting of impending death, often leads to increased symptom burden  compared to mild dehydration .Children with neurologic tumors may suffer frustrating decreases in their ability to communicate due to dysarthria, aphasia, or hearing deficits ,36. AssiN-Methyl-d-aspartic acid (NMDA) receptor antagonist properties and can be particularly efficacious in cancer related headache, but may necessitate consultation with a palliative care or pain specialist comfortable with dosing and monitoring [Headache occurs in around 36% of patients with brain tumors . The prinitoring . MethadoSeizures occur in 30–50% of patients with brain tumors. Seizures cause distress to the patient and family and may also cause worsening cognitive and behavioral functioning ,44. The For chronic seizure suppression, levetiracetam, as a broad acting staple, has few adverse effects, is well tolerated, and is often effective . Many paBecause neurologic tumors are associated with dysphagia, concentrated sublingual compounds and rectally administrated antiepileptic medications often become necessary. Pharmacists are an important resource in this regard. Diazepam is the primary rectal choice as it comes in a suppository and acts more quickly than other antiepileptics given by this route. Nausea and vomiting in the setting of pediatric neural tumors may be due to treatment or direct effects of the tumor. The vomit center receives input from two central nervous system controlling areas   and one Consider whether nausea is due to direct pressure from tumor, chemotherapy, toxins , vestibular pathology, or gastrointestinal pathology  . When thPain is reported by many children and adolescents with brain tumors, and may be due to the cancer itself, the treatments received, and the procedures performed . Most paOther manifestations of “total pain”  are addrTreatment of pain in the patient with neuro-oncological disease begins with the foundations of pain in other clinical care arenas: Assessment, identifying type of pain, intervention, and reassessment. Validated scales should be used whenever possible to track progress. The FLACC scale  is usefuThe two fundamental types of pain are nociceptive and neuropathic. Nociceptive pain includes somatic (muscle and bone) or visceral (organs) pain. Somatic pain is typically localized and described as “sharp”, “aching”, or “throbbing” whereas visceral nociceptive pain is poorly localized and described in a variety of ways . Neuropathic pain is typically due to damage to nerves and is described as “burning”, “needles”, or “numbness”, or is aggravated by touch . Much ofNonpharmacologic treatments should accompany the pharmacological approach for patients with any severity of pain; these include environmental changes, treating comorbid symptoms   dosing of morphine (or hydromorphone), beginning with an appropriate initial dose for weight and re-assessing response every 30 min. After each assessment using a validated pain assessment scale, additional morphine doses are given as follows: (1) If no relief and pain is >7, administer and increase dose by 50–100%, (2) if partial relief, but pain still >5, give one-half to 1 times the initial dose, and (3) if pain score is 4 or less, then no dose is given at the 30-min assessment. This process is repeated until the patient’s pain is 4 or less, or intolerable side effects occur. The total milligrams of opioid required to achieve pain control is calculated by dividing the total morphine dose given by the total number of elapsed hours since initiation of the pain titration, thus providing the hourly morphine rate. With this information, one can calculate an equivalent daily methadone dose, fentanyl patch, or a basal morphine IV/SQ infusion rate. Breakthrough pain treatment with additional doses of morphine are then added at 20% of the daily morphine dose and offered every 3 h IV prn. Alternatively, a patient-controlled analgesia (PCA) pump can be started with a morphine basal rate equivalent to the calculated hourly morphine rate, an added “PCA” or “demand” dose of 100% of the hourly rate (range 50–200%) and a timed “lock-out” of 10 min. Re-assessment of pain should occur multiple times per day; increases in pain and opioid use should be followed by dose adjustments. In the terminal setting, it is not uncommon for 80% of the daily opioid used each day to be delivered continuously via methadone or an IV opioid infusion, and for patients to need a twice daily upward titration . ContinuAdvantages of PCA use include: (1) The ability of patients to titrate pain medication to relief; (2) reduced delay in addressing changes in pain intensity; and (3) gives children and young adults some control over their symptom management. Contraindications to the use of PCA are all relative in the end-of-life setting. However, PCA is not an ideal delivery mechanism for patients that are delirious, encephalopathic, or physically unable to press the demand button. If the patient is actively dying, and goals of care are well established, and comfort-directed, then PCA by-proxy (nurse or family member) is appropriate and an often-optimal way to provide pain management . Common opioid side effects include pruritis, nausea, sedation, and constipation. In general, sedation is dose-related and should be avoided, except at end-of-life if consistent with goals. Constipation should be anticipated with all opioids except methadone, and prophylaxis is appropriate in the setting of “around the clock” opioid treatment. Orders for antihistamine are also indicated for as needed use for pruritis. Nausea can be treated with antiemetics. In general, when side effects are not tolerated, opioids can be rotated as patients respond differently to different opioids and, in general, hydromorphone is less likely to cause pruritis than morphine. When rotating opioids, the equivalent opioid dose should be calculated and then reduced by 25% to account for incomplete cross-tolerance. See Reassessment is critical to pain control and should be performed at a frequency consistent with the medications used (consider expected time-to-onset and duration of action) and pain severity. Children suffering pain deserve aggressive pain control, which may require escalating doses of opioids significantly and rapidly. There is no empiric upper limit dose on opioids; however, an individual may reach their upper limit when he/she experiences increased side effects without additional benefit to pain control . The treNeuropathic pain in children is treated primarily with gabapentinoids, and/or tricyclic antidepressants, which decrease central nervous system (CNS) excitatory neurotransmission . Again, Though beyond the scope of this text, pain management can also include palliative radiation and surgical approaches, such as dorsal rhizotomy. Consultation with radiation oncology, neurosurgery, pain medicine, and/or hospice and palliative medicine specialists is prudent in patients with recalcitrant pain. In the rare case where pain control cannot be achieved, the goals-of-care may be consistent with palliative sedation, which necessitates consultation with palliative care specialists ,76,77,78As brain tumors progress, they often (in 60% of children) cause mood changes, such as depression or anxiety, which are important , yet undFor moderate symptom burden, cognitive behavior therapy in addition to medications, such as selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants, should be initiated and selected primarily based on the secondary beneficial effects . For severe mood symptoms, medications and supportive therapies should be initiated together, psychology and/or psychiatry consultation should be obtained, and disposition should be considered .Children and adolescents laden with symptoms and the weight of disease, may express their burden through requests for a hastening of death. American Academy of Pediatrics (AAP) guidelines do not support physician-assisted-death; the request should be met with normalization, compassionate care, and an aggressive focus on relieving burdens and increasing quality of life ,92,93. PMany patients with brain tumors demonstrate agitation, or delirium ,41,47.Agitation can be caused by direct tumor effects, medical complications , and medications . Benzodiazepines  at the lowest possible dose are the primary treatment, especially if anxiety is present, followed by neuroleptics , and alpha-agonists (clonidine) . NeuroleAn altered mental status is the most common symptom as children with tumors of the brain approach death  ,47. ThisPalliative care teams maintain the goal of caring not only for the patient, but also for the entire family as they grieve and bereave . The comWhile oncology, palliative care, and other interdisciplinary teams have matured areas of disease and symptom management, families report significant deficiencies in psychological care near the end of life . Many faSimilarly, regardless of the prognosis or the choices in care that parents select, disease-specific or pediatric oncological support communities can provide a community, validation, and education to the entire family unit; providers should try to connect families to such a group whenever possible.Pediatric patients suffering from CNS tumors face difficult clinical decisions and carry a significant symptom burden. Given the high risk of mortality, communication of prognosis and goal-setting can be challenging. Supporting caregiver decision making requires honest, empathic communication and attention to the family values and emotions. Ongoing symptom assessment and management is a must to optimize quality of life and reduce suffering. Providers caring for these children should have a basic knowledge of palliative communication skills and pain and symptom management, with access to specialist palliative care providers as needed.


Introduction: Breast surgery is associated with persistent postsurgical pain; usually related to poorly treated acute pain. Paravertebral block has been successfully employed in analgesic protocols for breast surgery; its impact on postdischarge pain (PDP) has not been investigated. The aim of this study was to assess characteristics of PDP after breast surgery, the development of chronic postoperative pain (CPP) and its impact on health care costs.Methods: We conducted a retrospective, observational study on a continuous cohort of adult female patients undergoing local breast cancer surgery under combined anesthesia. All patients were interviewed 6 months after hospital discharge. The survey was specifically conceived to assess incidence, features and duration of PDP. The overall cost of additional healthcare resources consumed with a specific relationship to persistent PDP was estimated.Results: A database of 244 patients was preliminarily analyzed. Of these, 188 were included in the following statistical analysis; 123 patients (65.2%) reported significant PDP, with a median intensity on NRS of 6 (IQR=2), more frequently described as burning and associated with paresthesia and/or hyperalgesia . One hundred and six patients (56.5%) reported this pain as interfering with their normal daily activities, work and sleep. In 26.8% of cases (50 patients) symptoms lasted more than 1 month and in 28 patients (15.0%) pain became chronic. The majority of patients self-treated their pain with non-steroideal anti-inflammatory drugs, but in 50 patients (26.8%) this therapy was reported as ineffective. This additional consumption of healthcare resources led to a significant economical impact.Conclusion: PDP and CPP seem to be common complications after breast cancer surgery, even if a combined anesthesia technique with a thoracic paravertebral block is performed, leading to severe consequences on patients’ quality of life and increasing consumption of healthcare resources after discharge.Trial number: NCT03618459 . Breast cancer is the most frequently diagnosed tumor in women, with an incidence of more than one million new cases per year.6Development of chronic postbreast surgery pain is associated with some potential risk factors.8Recently, the awareness of the social impact of untreated postoperative pain is broadening the debate regarding the translation from chronic wound pain to persistent postoperative pain;9A Cochrane systematic review has addressed the role of regional anesthesia in preventing the development of CPP, suggesting that “paravertebral block may reduce the pain after breast cancer surgery in about one out of five women treated“, these results being however weakened by a poor quality or an inadequate power of the studies included.11Even though CPP has been progressively recognized as a significant clinical issue after breast cancer surgery,We performed a retrospective observational study on a consecutive cohort of female adult patients who underwent local breast cancer surgery with a standardized combined anesthesia technique, including a standardized single-shot thoracic paravertebral block performed before surgery with a long-lasting local anesthetic and general anesthesia, which is described in more detail in the section below.As part of the local quality survey aimed at assessing patients’ satisfaction with specific regard to the quality of postoperative analgesia after breast surgery, all patients undergoing breast cancer surgery were systematically telephone interviewed 6 months after hospital discharge. The survey, conducted after the inclusion of paravertebral block in the postoperative analgesia protocol for breast cancer surgery, was specifically aimed at assessing, besides overall satisfaction, the incidence, features and duration of an eventual PDP. Answers to the questionnaire were anonymously registered in an electronic database.After approval by the Institutional Review Board of the Hospital Ospedale Regionale di Bellinzona e Valli, an observational retrospective cohort study was conducted on the results of the survey. The study was registered on Clinicaltrial.gov (number NCT03618459) and was carried out according to the principles of the Declaration of Helsinki. Inclusion criteria for the analytic cohort were: 1) consecutive ASA 1–3 adult female patients, 2) elective local breast surgery, namely unilateral tumor resections, lumpectomies or mastectomies, without axillary lymphadenectomy, 3) under a combined anesthesia with a standardized single-shot thoracic paravertebral block and 4) who completed the telephone interview 6 months after surgery. Patients were excluded if any data at any time regarding their pain evolution and medications were incomplete.H3 and TH4 level using an in-plane approach with a 5 cm needle , according to a standardized procedure. After a preliminary orientation scan aimed at identifying the correct levels and prior to the procedure, skin disinfection was performed with a two-layer application of an alcoholic povidone-iodine solution . Three minutes later, the area of the puncture point was covered with sterile drapes. After confirmation of correct positioning of the needle tip with the administration of a small bolus of normal saline under ultrasound guidance and after negative aspiration, two boluses of 10 mL of ropivacaine 0.75%  were administered both at TH3 and TH4, for a total volume of 20 mL, under real-time ultrasound visualization. Block success was subsequently evaluated with thermal sensation testing: a block was defined as successful when associated with a complete loss of cold perception overall dermatomes involved in the planned surgery 20 mins after local anesthetic injection.All patients underwent the same standardized anesthetic treatment, according to a specific protocol. After arrival in the preoperative induction room, standard monitoring and peripheral venous access were attained. A standard procedural intravenous analgesia and sedation was administered, with 1 μg/kg of fentanyl and 1–2 mg of midazolam. All patients underwent an ultrasound-guided unilateral thoracic paravertebral block both at TThereafter, total intravenous anesthesia was induced after further administration of 1–2 mcg/kg of fentanyl prior to laryngeal mask placement. During general anesthesia, all patients received a single dose of diclofenac 75 mg and paracetamol 1 g intravenously as per local protocol. Systemic postoperative analgesia with oral diclofenac (50 mg tid) and paracetamol (1 g qd) was always prescribed during the whole hospital stay., sufficient, good or perfect. The analgesic protocol was considered as effective when patients evaluated their analgesia as sufficient, good or perfect.Data were collected with a specific questionnaire, including information such as the date of surgery, type and site of surgery, and basal patients’ demographic data. Patients were subsequently contacted by phone at home, 6 months after surgery, concerning their pain’s evaluation and the adequacy of own postoperative analgesia during the first 24 hrs after surgery, stratifying it into categorical variables as insufficientPatients were subsequently asked to discuss the occurrence of PDP. PDP was evaluated by Numerical Rating Scale , defining “pain” any ache referred as “more than 2”. Data regarding PDP duration and its characteristics , localization , impact on daily life activity  and treatment  and/or oral opioids) were registered.The primary outcome of the study was the incidence of PDP. Secondary outcomes were: PDP characteristics, impact on patient daily life after discharge, and the correlation between PDP and the incidence of CPP, defined as wound pain a period of 3 months after surgery. Another secondary outcome was the postoperative healthcare costs associated with analgesic drugs consumption and consultations with the general practitioners related to pain issues.t-test was used for parametric data null hypothesis testing, while Mann–Whitney U-test was applied to non-parametric data. A P-value<0.05 was considered statistically significant (95% CI). Results are given as mean (m) ± SD for normally distributed parameters or median (M) and relative IQR for non-normally distributed parameters. A Chi-square test was performed in order to evaluate any statistical correlation between PDP and CPP. The economic analysis was performed assuming the point of view of the community. Postdischarge healthcare costs were evaluated with a top-down technique by computing the costs of consultations by general practitioners  and analgesic drugs. The costs of lost working days due to pain-related disabilities were not taken into account. Costs were expressed in USD. Statistical analysis was performed using SPSS  and Numbers ’09 2.1 version  software. All data were collected and stored anonymously in an electronic protected database.Unpaired Student's Of 244 consecutive questionnaires, 56 were excluded because incomplete, while 188 were considered in the final analysis. The main characteristics of the population were: mean age 58.9±14.6 years, median ASA class 2 (IQR=1) and mean length of hospital stay 6±1 days.After discharge at home, 70.2% (N=132) of patients referred localized  or regional PDP radiating to the ipsilateral arm . Median Regarding efficacy of acute pain treatment the day after surgery, patients evaluated their analgesia at awakening from general anesthesia as perfect in 49%, good in 38%, sufficient in 10% and inadequate in 3% of cases . Acute pIn 26.6% of patients (n=50), PDP persisted for more than 1 month and in 14.9% (n=28) pain became chronic, longer than 3 months duration; in 8.5% of these (n=16), PDP was still present during the interview . Good inp<0.001).A high correlation was found between PDP and the development of CPP: all patients  developing a CPP referred to having suffered from PDP immediately after home discharge. No patient who was PDP-free after discharge subsequently developed a CPP  treated their pain with a combination of paracetamol and NSAIDs – the most common was diclofenac; in 26.7% of cases (50 patients) this therapy was ineffective and 18.8% of patients went to their general practitioner for a consultation related to their PDP. During the first 6 months postoperatively, postdischarge costs of home-based systemic analgesia and eventual general practitioner consultations related to pain issues were significantly higher in patients with PDP compared to patients without PDP, with an estimated increase in healthcare related costs per patient over the first 6 postdischarge months of 1,367 USD, due to medications (about 900 USD for 6 months) and consultation with general practitioners specifically attributable to PDP or PDP-related issues (about 400 USD during 6 months).The preventive role of regional anesthesia on CPP in relation to its effective control of acute pain has often been postulated. Hussain et al,A single shot paravertebral block seems to be a good choice to provide effective in-hospital analgesia during the first days after surgery, but does not seem to prevent the development of PDP in the following period.PDP duration was extremely variable, often lasting for many weeks after surgery and evolving into chronic pain syndrome in 15% of cases. Patients generally attempted to self-medicate PDP with NSAIDs, treatment turning out to be ineffective and leading eventually to a visit to the family practitioner, with an obvious impact on patient’s life quality and total healthcare costs.Previous studies focused on CPP incidence, while this is the first study specifically addressing PDP after local breast surgery, with the aim of quantifying and characterizing this condition, its dimension and gravity of which was found to be a potentially important healthcare issue. Our finding supports the hypothesis that, even when a good anesthetic plan is routinely adopted and includes regional anesthesia technique such as a single shot-paravertebral block with a long-lasting local anesthetic, PDP is not prevented. Moreover, CPP whose incidence is still high in this specific group of patients is also not prevented by a single-shot paravertebral block.PDP in breast surgery patients seemed to have specific neuropathic features, which is a significant subgroup of patients interviewed had an important and prolonged impact on quality of life and possibly on postdischarge healthcare costs, ultimately causing a sustained use of analgesic drugs and consultations by general practitioners for pain-related issues. It is important to notice that our patients were not enrolled in a fast-track program and stayed in the hospital for several days before discharge home. During their hospitalization, they received systemic analgesia with NSAID, paracetamol and rescue opioids on demand, according to a standard protocol. However, even if patients remained in hospital and were monitored for days, being regularly treated with analgesic drugs, PDP and the development of CPP were not prevented.Chronic pain is well known to be a public health issue: 22% of US primary care appointments focus on pain management, and a linear trend of specific national pain consultations has been reported,17Further studies are required to define effective strategies to treat postoperative pain after breast surgery specifically aiming at preventing PDP, eventually decreasing the incidence of postoperative chronic pain. Regional anesthesia as well as the preventive use of systemic drugs, such as ketamine, have been shown by some preliminary evidence to be possibly associated with a reduction in chronic pain incidence;Our study has several limitations. Firstly, this was a single-center retrospective study, including all relative drawbacks compared to prospective randomized trials. Secondly, only one analgesic management was studied, making results applicable only to this therapeutic management, even if the paravertebral block is considered as an advanced technique to control acute pain after breast surgery. Moreover, our study does not stratify patients with regard to eventual postoperative treatments which may potentially influence the intensity, the characteristics and the duration of postoperative pain, such as radiotherapy.For the assessment of the characteristics of PDP, we did not use a validated scale , as we wanted to focus on a combination of factors, assessing the duration, the intensity and the characteristics of pain. Another limitation is that, in order to adequately assess PDP and CPP incidence, our questionnaire was performed 6 months after hospital discharge, which might have affected patients’ accuracy in assessing their pain. However, this may also represent an advantage with regard to the possibility of giving a more detached and unbiased evaluation of their entire postoperative experience overall.PDP and CPP seem to be common complications after breast surgery even when a general anesthesia technique is combined with a single-shot thoracic paravertebral block. Given the impact of these complications on the patients’ quality of life and healthcare costs, alternative analgesic strategies and a proper follow-up seem to be recommendable, in order to prevent or early detect and adequately treat PDP.