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Fredrik Hetmann,1 Ulf E Kongsgaard,2,3 Leiv Sandvik,4 Inger Schou-Bredal3,5 1Department of Nursing and Health Promotion, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, 2Division of Emergencies and Critical Care, Department of Anaesthesiology, Oslo University Hospital, 3Medical Faculty, University of Oslo, 4Department of Biostatistics and Epidemiology, Division of Oslo Hospital Services, 5Department of Breast and Endocrine Surgery, Division of Cancer and Surgery, Oslo University Hospital, Oslo, Norway Background: Persistent pain affects a large proportion of patients after thoracotomy and is associated with sensory disturbances. The objective of this prospective study was to investigate the time course of pain and sensory disturbances over a 12-month period. Methods: Patients scheduled for thoracotomy were recruited. Data were collected on the day before surgery, including baseline characteristics and the presence of any preoperative pain. At 6- and 12-month follow-ups, data on pain were collected using the Brief Pain Inventory-Short Form, and perceived sensory disturbances around the thoracotomy scar were recorded from a self-exploration test. Results: At 12 months after surgery, 97 patients had complete data including baseline and 6- and 12-month measurements. Almost half of the patients reported post-thoracotomy pain at the follow-ups. However, 20% of the patients not reporting post-thoracotomy pain at 6 months did report it at 12 months. Between 40% and 60% of patients experienced some kind of sensory disturbance at 6 months. A small decline in some kind of sensory disturbance was reported by 20%–50% of patients at 12 months. Conclusion: A proportion of patients experienced either resolved or delayed onset of pain. Sensory changes were strongly associated with post-thoracotomy pain syndrome, but were also present in a large proportion of patients without it. Keywords: pain, post-thoracotomy pain syndrome, chronic pain, thoracic surgery, sensory disturbance, delayed pain

Andrey L Melnikov,1 Steinar Bjoergo,1 Ulf E Kongsgaard21Department of Anesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway; 2Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital and Medical Faculty, University of Oslo, Oslo, NorwayBackground and objectives: Patients undergoing abdominal surgery often receive an epidural infusion for postoperative analgesia. However, when epidural analgesia is contraindicated or unwanted, the administration of opioids is the usual means used to relieve pain. Various regional analgesia techniques used in conjunction with systemic analgesia have been reported to reduce the cumulative postoperative opioid consumption and opioid-induced side effects. The objective of this trial was to assess the effectiveness of transversus abdominis plane block and paravertebral block in women undergoing major gynecological surgery.Methods: We analyzed 58 patients scheduled for a midline vertical laparatomy due to gynecological cancer. They were all equipped with a patient-controlled postoperative analgesia pump that delivered ketobemidon. In addition, some patients were randomized to receive either a bilateral transversus abdominis plane block (n = 19) or a bilateral paravertebral block at the level of Th10 (n = 19). Both blocks were performed preoperatively as a single injection of bupivacaine.Results: Cumulative ketobemidon consumption, postoperative pain scores at rest and while coughing, and postoperative nausea and vomiting scores were assessed by a blinded observer at 2, 4, 6, 24, and 48 hours postoperatively. Both blocks were associated with significant reductions in opioid consumption and pain scores throughout the study period compared with the control patients. Postoperative nausea and vomiting scores were low in all groups, but during the early postoperative period more control group patients needed antiemetics.Conclusion: Both methods of inducing block can serve as effective analgesia adjuncts in women undergoing major gynecological surgery. Although thoracic paravertebral block appeared to be more effective than transversus abdomins block, the latter performed under ultrasound guidance seems to be a more controlled and safe alternative.Keywords: hysterectomy, transversus abdominis plane block, paravertebral block, postoperative pain

Background: Pelvic radiation therapy is an important element of curative therapy for gynaecological cancers. Serious radiation-related complications developing months or years after treatment are known as late radiation tissue injury (LRTI).Methods: We investigated the possible pain reducing effect of hyperbaric oxygen treatment (HBOT) in a study of 16 patients with LRTI after radiation for gynaecological malignancy. The 16 patients were registered prospectively, underwent HBOT for 21 consecutive days and were followed for a 6-month period after treatment using the Brief Pain Inventory, Montgomery and Aasberg Depression Rating Scale, as well as registration of global patient scores, analgesic consumption and magnetic resonance imaging (MRI) findings.Results: HBOT was shown to have insignificant effect on pain, pain characteristics, daily function, the use of analgesics and MRI-related tissue injury. Fifty percent of the patients still reported some or good effect of the treatment.Conclusion: It is not possible to conclude from our study if gynaecological patients with pelvic pain will benefit from HBOT. The application of HBOT to selected patients may be justified, but further research with adequate sample size, as well as the timing of HBOT related to the development of LRTI, is required to establish the optimum patient selection. [ABSTRACT FROM AUTHOR]

In the United States, quality improvement (QI) approaches have been used to evaluate pain management. However, the use of QI approaches to evaluate the quality of patient care is just emerging in many European countries. The purposes of this study, using the American Pain Society's QI Standards, were: to describe changes over time, in pain severity, in pain interference with function, and in the doses of analgesics administered; to describe patients' level of satisfaction with postoperative pain management; and to determine the relationships between pain severity and patient outcomes. Results from a sample of patients who underwent orthopedic surgery suggest that undertreatment of pain persists across the first 5 postoperative days and that pain's level of interference with function decreases significantly between the third and fifth postoperative days. As in other studies, despite high pain intensity scores, patients reported high levels of satisfaction with postoperative pain management. PERSPECTIVE: Findings suggest that the undertreatment of pain results in significant decrements in function over the first 5 postoperative days. Future studies designed to improve the quality of postoperative pain management need to use multimodal approaches and evaluate not only pain intensity, but improvements in function as critical outcome measures. [ABSTRACT FROM AUTHOR]

Background: Interpreting opioid concentrations is challenging because of the lack of reference ranges. Therefore, the authors aimed to propose dose-specific concentration ranges in serum for oxycodone, morphine, and fentanyl in patients with chronic pain, based on concentration measurements from a large number of patients and supported by theoretical pharmacokinetic calculations and previously published concentrations., Methods: The opioid concentrations in patients undergoing therapeutic drug monitoring (TDM) for various indications (TDM group) and patients with cancer (cancer group) were investigated. Patients were divided based on the daily opioid doses, and the 10th and 90th percentiles of the concentrations in each dose interval were evaluated. In addition, the expected average serum concentrations were calculated for each dose interval based on published pharmacokinetic data, and a targeted literature search for previously reported dose-specific concentrations was performed., Results: The opioid concentrations in 1054 patient samples were included: 1004 in the TDM group and 50 in the cancer group. In total, 607 oxycodone, 246 morphine, and 248 fentanyl samples were evaluated. The authors proposed dose-specific concentration ranges based mainly on 10th-90th percentiles of the concentrations measured in patient samples, whereas the calculated average concentrations and previously published concentrations were used to adjust the ranges. In general, results from calculations and concentrations retrieved from previous literature were within the 10th-90th percentiles of concentrations from patient samples. However, the lowest calculated average concentrations of fentanyl and morphine were below the 10th percentiles of patient samples in all dose groups., Conclusions: The proposed dose-specific ranges may be useful for interpreting steady-state opioid serum concentrations in clinical and forensic settings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The cohort of critically ill patients transported between Intensive Care Units (ICUs) in Norway has not been studied previously. The aim of this study was to describe the characteristics of patients and transports for different types of interhospital transfers and explore whether there were differences in morbidity and mortality between the different transfer categories and the general Norwegian ICU population., Methods: All transports of critically ill adult patients transferred between two geographically different Intensive Care Units during a one-year period were registered. Patient and transport data were obtained from The Norwegian Intensive Care Registry, The Norwegian Cause of Death Registry, the hospital Electronic Patient Journal, the Air Ambulance Journal System, and the Emergency Medical Communication Centre database., Results: 821 transports of 788 surgical and medical patients were enrolled. Simplified Acute Physiology Scores (SAPSII) were 43, 36 and 38 for urgent secondary transport, non-urgent secondary transport and return transfers, respectively. These were comparable to nationwide SAPSII scores that were 40 for university hospitals and 34 for local hospitals during the same time period. The return transfers had a median SOFA-score of 4.7 and 53% were mechanically ventilated. Only 33% of return transfers were performed by established teams., Conclusion: Intensive care patients transferred between ICUs are as critically ill as the rest of the ICU population, with a similar morbidity and mortality. The return transfers of ICU-patients appear under-triaged compared to secondary transports in terms of allocated resources., (© 2021 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Objectives: The out-of-hospital environment can pose significant challenges to the quality and safety of interhospital transport of critically ill patients. Because we lack knowledge of the occurrence of incidents, their potential consequences, and whether they are actually reported, this study was initiated., Methods: Two different services in Norway were asked to self-report incidents after every interhospital transport of critically ill patients. Sampling lasted for 12 and 8 months, respectively. An expert group evaluated each incident for severity and demand for reporting into the hospital's electronic incident reporting system. One year later, the hospital's reporting system was scrutinized to determine the number of incidents actually reported., Results: A total of 455 transports of critically ill patients were performed, resulting in 294 unique incidents reported: medical (15%), technical (25%), missing equipment (17%), and personal failures and communication difficulties (42%). Only 3 (1%) of the 294 unique incidents were actually reported in the hospital's electronic incident reporting system. The experts were inconsistent in which incidents should have been reported and to what degree checklists, standard operating procedures, simulation, and training could have prevented the incidents., Conclusions: This study of interhospital transports of critically ill patients reveals a very high number of incidents. Despite this fact, these incidents are severely underreported in the hospital's electronic incident reporting system. This suggests that learning is lost and errors with predominant probability are repeated. These results emphasize the existing challenges in regard to the quality and safety of interhospital transport of critically ill patients., Competing Interests: H.E. received funding from The Norwegian Air Ambulance Foundation. For the remaining authors, no conflicts of interest were declared., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and aims Pupil size and reaction are influenced by opioids, an effect that is not considered to be affected by opioid tolerance. As clinicians have observed patients on high-dose opioids who exhibited seemingly normal pupil sizes, we wanted to dynamically assess the pupillary reflex in cancer patients on high-dose opioids. Methods We performed a dynamic assessment of the pupillary reflex in cancer patients on high-dose opioids and a control group of healthy volunteers using a portable, monocular, infrared pupillometer. We also performed a clinical examination and measured blood concentrations of opioids and their active metabolites. Results Sixty three patients who were on opioids for 2 months (median time) and on an oral morphine equivalent dose of 250 mg (median dose) were investigated. Most patients used more than one opioid. When correcting for age, pupil size in the group that had received no increase of opioid dose over the last 14 days was not significantly different from pupil size in the healthy volunteer group (p = 0.76), while the group that had increased the dose of opioids differed significantly from healthy volunteers (p = 0.006). We found no statistically significant correlation between total oral morphine equivalents and pupillary reactions or between blood opioid or opioid metabolite concentrations and baseline pupillary changes. Conclusion Pupillary changes do take place in patients on opioids. However, tolerance to these changes occurs when medication is not increased over time. Dynamic pupillometry can give additional information about the degree of tolerance to opioids. Implications These findings elucidate previous misconceptions regarding pupillary effects and tolerance to opioids.

Background: No consensus based national standard for interhospital transports of critically ill patients exists in Norway. The local hospitals are responsible for funding, organizing and performing these transports, resulting in potentially different level of care for the critically ill patients depending on local hospital resources and not the level of severity in the patient's condition. The aim of this study was to examine how these transports are executed and to discover challenges during transports and potentials of improvement., Methods: A qualitative study with 20 semi-structured interviews of doctors, nurses and ambulance personnel representing a wide range in experience and formal education, reflecting the different compositions of crews performing interhospital transports was conducted. A systematic text condensation of the interviews was performed to describe personal experiences and values., Results: Few interviewees reported special adverse events when asked. Instead they chose to describe more general characteristics of the working environment, their own positive emotions or fears and the strengths and weaknesses of the organizational system. The prehospital working environment was described as different from the in-hospital environment. The personnel experienced being on their own during transports, lack of procedures and checklists and often no systematic education or demanded preparedness for participating. The resident doctors described pressure from elderly colleagues to participate in the transports. At the same time, all interviewees reported a self-interest in participating in these transports., Conclusions: Safe interhospital transports of the critically ill patients are challenged by the characteristics of the out of hospital environment. The transports are described as potentially unsafe for both patients and personnel. Systematic education is warranted, highlighting the use of checklists and special educational programs in prehospital critical care medicine. The strong personal interest to participate in these transports may serve as a barrier against changing todays system. To ensure the right level of competence and safety for each unique patient, it is imperative to standardize the interhospital transports on a national level, built on consensus from experienced prehospital personnel., Trial Registration: The trial is approved and registered by the local representative for the Norwegian Data Protection Authority as trial 13-7751.

Background: Administration of resuscitation fluid is a common intervention in the treatment of critically ill patients, but the right choice of fluid is still a matter of debate. Changes in medical practice are based on new evidence and guidelines as well as traditions and personal preferences. Official warnings against the use of hydroxyl-ethyl-starch (HES) solutions have been issued. Nordic guidelines have issued several strong recommendations favouring crystalloids over colloids in all patient groups. Our objective was to describe the patterns of colloid use in Nordic countries from 2012 to 2016., Methods: The data were obtained from companies that provide pharmaceutical statistics in different countries. The data are sales figures from pharmaceutical companies to pharmacies and health institutions., Results: We found a 56% reduction in the total sales of all colloids in Nordic countries over a 5-year period. These findings were mainly related to a 92% reduction in the sales of HES solutions. A reduction in sales of other synthetic colloids has also occurred. During the same period, we found a 46% increase in albumin sales, but these numbers varied between Nordic countries., Conclusion: The general reduction in colloid sales likely reflects the recommendation that colloids should be used only in special circumstances. The dramatic reduction in the sales of HES solutions was expected given evidence of harm and the official warnings. The steady increase in albumin sales and the notable differences between the five Nordic countries cannot be explained., (© 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Securing the airway is one of the most important responsibilities in anaesthesia. Injuries related to airway management can occur. Analysis from closed claims can help to identify patterns of injury, risk factors and areas for improvement., Methods: All claims to The Norwegian System of Compensation to Patients from 1 January 2001 to 31 December 2015 within the medical specialty of anaesthesiology were studied. Data were extracted from this database for patients and coded by airway management procedures., Results: Of 400 claims for injuries related to airway management, 359 were classified as 'non-severe' and 41 as 'severe'. Of the severe cases, 37% of injuries occurred during emergency procedures. Eighty-one claims resulted in compensation, and 319 were rejected. A total of €1,505,344 was paid to the claimants during the period. Claims of dental damage contributed to a numerically important, but financially modest, proportion of claims. More than half of the severe cases were caused by failed intubation or a misplaced endotracheal tube., Conclusion: Anaesthesia procedures are not without risk, and injuries can occur when securing the airway. The most common injury was dental trauma. Clear patterns of airway management that resulted in injuries are not apparent from our data, but 37% of severe cases were related to emergency procedures which suggest the need for additional vigilance. Guidelines for difficult intubation situations are well established, but adherence to such guidelines varies. Good planning of every general anaesthesia should involve consideration of possible airway problems and assessment of pre-existing poor dentition., (© 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: There has been a steady increase in cases reported to the Norwegian System of Patient Injury Compensation (NPE). We wished to look into what might characterise those cases of central and peripheral nerve blockade for anaesthesia that led to compensation claims., Material and Method: Cases with codes for central and peripheral blockade within the field of anaesthesiology were retrieved from the NPE database for the period 2001 – 14. The cases were evaluated on the basis of variables including sex, age, type of anaesthesia, diagnosis, type of injury, site of injury, damages received, and written descriptions of treatment and injury. The expert reports were anonymised and reviewed in detail., Results: A total of 339 patient compensation claims relating to nerve blockade were identified, of which 149 concerned spinal anaesthesia, 142 epidural anaesthesia, 21 combined spinal and epidural anaesthesia and 27 peripheral nerve blockade. The group consisted of 236 women and 103 men, and the average age was 46 years. The 339 cases comprised 0.8 % of all cases reported to the NPE in this period. A total of 107 claims resulted in compensation. Eighty-two million Norwegian kroner were paid out in total., Interpretation: Peripheral and central nerve blockade accounts for only a small proportion of cases handled by the NPE. Only one in three applicants had their claim upheld, but when claims were upheld, the injuries were often severe and led to substantial pay-outs.

Background and Aims: Opioid-induced bowel dysfunction (OIBD) is an increasing problem due to the common use of opioids for pain worldwide. It manifests with different symptoms, such as dry mouth, gastro-oesophageal reflux, vomiting, bloating, abdominal pain, anorexia, hard stools, constipation and incomplete evacuation. Opioid-induced constipation (OIC) is one of its many symptoms and probably the most prevalent. The current review describes the pathophysiology, clinical implications and treatment of OIBD., Methods: The Nordic Working Group was formed to provide input for Scandinavian specialists in multiple, relevant areas. Seven main topics with associated statements were defined. The working plan provided a structured format for systematic reviews and included instructions on how to evaluate the level of evidence according to the GRADE guidelines. The quality of evidence supporting the different statements was rated as high, moderate or low. At a second meeting, the group discussed and voted on each section with recommendations (weak and strong) for the statements., Results: The literature review supported the fact that opioid receptors are expressed throughout the gastrointestinal tract. When blocked by exogenous opioids, there are changes in motility, secretion and absorption of fluids, and sphincter function that are reflected in clinical symptoms. The group supported a recent consensus statement for OIC, which takes into account the change in bowel habits for at least one week rather than focusing on the frequency of bowel movements. Many patients with pain receive opioid therapy and concomitant constipation is associated with increased morbidity and utilization of healthcare resources. Opioid treatment for acute postoperative pain will prolong the postoperative ileus and should also be considered in this context. There are no available tools to assess OIBD, but many rating scales have been developed to assess constipation, and a few specifically address OIC. A clinical treatment strategy for OIBD/OIC was proposed and presented in a flowchart. First-line treatment of OIC is conventional laxatives, lifestyle changes, tapering the opioid dosage and alternative analgesics. Whilst opioid rotation may also improve symptoms, these remain unalleviated in a substantial proportion of patients. Should conventional treatment fail, mechanism-based treatment with opioid antagonists should be considered, and they show advantages over laxatives. It should not be overlooked that many reasons for constipation other than OIBD exist, which should be taken into consideration in the individual patient., Conclusion and Implications: It is the belief of this Nordic Working Group that increased awareness of adverse effects and OIBD, particularly OIC, will lead to better pain treatment in patients on opioid therapy. Subsequently, optimised therapy will improve quality of life and, from a socio-economic perspective, may also reduce costs associated with hospitalisation, sick leave and early retirement in these patients., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Tachyphylaxis or acute tolerance to local anaesthetics has been reported, but the prevalence in clinical analgesia is obscure, and the mechanisms behind this phenomenon remain unclear. We sought to examine the clinical significance of tachyphylaxis from the available literature., Methods: We performed a systematic review of the literature utilising the databases PubMed and Embase employing the search terms [Tachyphylaxis AND Local Anaesthetics AND Human] AND [Tolerance AND Local Anaesthetics AND Human]., Results: A total of 66 records were identified. Thirty-four articles were assessed in full text for eligibility. Twenty studies were considered relevant for qualitative analyses, but only six studies were randomised controlled trials. Because of the heterogeneity of the randomised controlled trials, it was not possible to conduct a meta-analysis., Conclusion: Studies documenting tachyphylaxis with clinical use of local anaesthetics are surprisingly scarce, and the mechanisms behind it remain unclear., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Persistent post-surgical pain is recognised as a major problem. Prevalence after different surgical procedures has been reported to range from 5% up to 85%. Limb amputation and thoracotomy have the highest reported prevalence. Prediction of persistent post-surgical pain has over the last decade caught attention. Several factors have been investigated, but in-depth knowledge is still scarce. The purpose of this study was to investigate the prevalence of persistent post-surgical pain, and predictive factors for persistent post-surgical pain 12 months after thoracotomy., Methods: A prospective longitudinal study was conducted. One-hundred and seventy patients were recruited before scheduled thoracotomy, and asked to answer a questionnaire. One-hundred and six patients completed the same questionnaire at 12-month follow-up. Regression analysis was performed to explore variables assumed predictive of persistent post-surgical pain., Results: One-hundred and six patients (62%) filled out the questionnaire at both time points. Preoperative, 34% reported muscle-skeletal related chronic pain. At 12-month follow-up, 50% of the patients reported persistent post-surgical pain. Of the variables explored in the logistic regression model, only preoperative pain (P < 0.001) and dispositional optimism (P = 0.04) were statistically significant. In this study, preoperative pain was a predominant predictor for persistent postoperative pain (OR 6.97, CI 2.40-20.21), while dispositional optimism (OR 0.36, CI 0.14-0.96) seem to have protective properties., Conclusion: Our results show that preoperative pain is a predominant predictor of future pain. This implies that patients presenting with a chronic pain condition prior to surgery should be assessed thoroughly preoperatively and have an individually tailored analgesic regimen., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Epidural analgesia (EDA) is used widely for postoperative pain treatment. However, studies have reported a failure rate of EDA of up to 30%. We aimed to evaluate the quality of postoperative EDA in patients undergoing a laparotomy in five Norwegian hospitals., Methods: This was a multicenter observational study in patients undergoing a laparotomy with epidural-based postoperative analgesia. Data were registered at three time points. Technical aspects, infusion rates, pain intensity, assessment procedures, side effects, and satisfaction of patients and health personnel were recorded. The use of other pain medications and coanalgesics was registered., Results: Three hundred and seventeen patients were included. Pain control at rest was satisfactory in 89% of patients at 24 hours and in 91% at 48 hours. Pain control when coughing was satisfactory in 62% at 24 hours and in 59% at 48 hours. The spread of hypoesthesia was consistent for each individual patient but varied between patients. The hypoesthetic area was not associated with pain intensity, and the precision of the EDA insertion point was not associated with the pain score. Few side effects were reported. EDA was regarded as effective and functioning well by 64% of health personnel., Conclusion: EDA was an effective method for postoperative pain relief at rest but did not give sufficient pain relief during mobilization. The use of cold stimulation to assess the spread of EDA had limited value as a clinical indicator of the efficacy of postoperative pain control. Validated tools for the control of EDA quality are needed.

Purpose: Instanyl® (intranasal fentanyl spray) is a novel treatment for breakthrough pain (BTP) in cancer patients. It has shown a rapid onset of pain relief in clinical trials. This study examines the use of Instanyl® in real-life settings., Methods: A 3-month observational, prospective, cohort study of cancer patients with BTP receiving Instanyl® (50, 100, or 200 μg) under routine clinical practice. Data were collected at three time points corresponding with routine clinic visits - baseline, Week 4, and Week 13., Primary Outcomes: success of titration and maintenance dose after titration., Secondary Outcomes: change in maintenance dose of Instanyl® and level of background pain medication; Brief Pain Inventory--Short Form (BPI-SF) and Patient Treatment Satisfaction Scale (PTSS) scores; adverse drug reactions (ADRs)., Results: Titration with Instanyl® was successful in 84.5 % of 309 patients; most patients were titrated at the lowest dose (50 μg). The majority showed no change in maintenance dose, with little change in the level of background pain medication. BPI-SF and PTSS scores significantly improved from baseline to Week 4. The main reason for terminating Instanyl® was death, as expected due to the underlying disease; incidence of ADRs was low and no fatal ADRs were reported., Conclusions: In a real-life group of cancer patients with disease progression, Instanyl® was titrated successfully at doses <200 μg in the majority of patients, requiring only one dose, with no further change in maintenance dose. Pain severity, impact of pain on daily life, and treatment satisfaction significantly improved with Instanyl® treatment. No unexpected ADRs occurred.

Background: Despite advances in pain research, many patients still experience moderate to severe post-operative pain that needs to be alleviated. The primary aim of this study was to identify predictive factors for severe post-operative pain after thoracotomy. Secondary, we investigated the levels of post-operative pain in this group of patients., Methods: A prospective longitudinal study with 144 patients scheduled for thoracotomy was conducted between December 2007 and August 2010. All patients were given a questionnaire consisting of three sections (Brief Pain Inventory, Life Orientation Test-revised and Hospital Anxiety and Depression Scale) the day before surgery. Only those patients with pre-existing chronic pain were asked to complete all three sections. Post-operative pain scores were recorded three times a day for 6 days using the Numeric Rating Scale, and all analgesic consumption was recorded daily., Results: Fifty-four patients reported pre-existing pain before surgery, most commonly from the neck, shoulders, lower back, hips or knees. For the first 3 days after surgery, the pain scores for those who had pre-existing chronic pain and those who did not, where almost similar with no statistically significant difference. The total amount of the epidural analgesia-mixture used where also almost similar for both groups with no statistically significant difference., Conclusion: In contrast to previous studies, which have reported pre-operative chronic pain to be a strong predictor of moderate to severe post-operative pain, we have in our study not been able to replicate these findings., (© 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: The pharmacokinetics of the immunosuppressant mycophenolic acid (MPA) demonstrates high inter- and intra-patient variability. Variation in the binding of MPA to albumin has been postulated to be an important factor in this variability, and monitoring of free MPA has been suggested to improve therapeutic drug monitoring (TDM) of MPA. Inosine monophosphate dehydrogenase (IMPDH) is the target enzyme for MPA, therefore the IMPDH activity in lymphocytes can serve as a marker of the MPA-specific response. This study aimed to explore how the albumin concentration influences the free concentration of MPA in liver transplant recipients and to assess whether alteration in the free MPA influences IMPDH activity in CD4 + cells., Methods: Blood samples were taken from 20 liver transplant recipients on two separate occasions (days 3-5 and 16-21). Total and free concentrations of MPA, and IMPDH activity were measured during the first 4 h of each dose interval., Results: Albumin levels correlated with the free fraction of MPA. However, the total MPA and free MPA were equal predictors of the immunosuppressive response as defined by IMPDH activity., Conclusion: Total and free MPA are equally good predictors of the immunosuppressive effect exerted by MPA as defined by IMPDH activity. IMPDH activity measurements represent a promising approach to TDM in patients treated with MPA.

Purpose of the Research: Breakthrough cancer pain (BTCP) is a prevalent type of pain in which the nurse can play an important role in improving patients' pain symptoms and overall well-being. Nurses' experience with BTCP (number of patients, and estimates of severity and frequency), the treatment of BTCP (pharmacological and nonpharmacological treatments normally used), ratings of the importance of treatment factors, and reasons given for not advising patients to take strong painkillers are presented in the present paper., Methods and Sample: Nurses from 12 European countries, who cared for patients with cancer, took part in a survey. In total 1618 nurses were recruited and 1241 completed the survey questionnaire., Key Results: Almost 90% of the nurses were female, and 50.4% had >9 years of experience in oncology nursing. The majority of the nurses (47%) said that a patient typically suffered from BTCP 2-3 times a day, and the severity of the pain for the patients was described as severe by 75.5%. In all, 38.4% of the nurses were unaware that medications specifically intended for treatment of BTCP exist, and 57% reported that oral opioids were normally prescribed for BTCP at their workplace. While 38% said they did not use nonpharmacological treatments for BTCP, the most common treatment approach was positional change (used by 76.6%). The treatment varied between the European countries., Conclusion: Patients do not receive the appropriate medical treatment for their BTCP. Nurses need better training about BTCP in general, and BTCP assessment and management specifically., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: In 2010 we celebrated the bicentennial of Chopin's birth. He left more than 230 fantastic compositions, often described as romantic, emotional and poetic. Chopin composed almost exclusively for piano solo and has been called the pianists' composer. From his teens he suffered from respiratory tract infections, gradually accompanied by haemoptysis, pronounced breathing problems, diarrhoea and loss of weight. He experienced part of his adult life as a period of great suffering. He was 39 years old when he died. The assumed cause of death was tuberculosis, but other possible differential diagnoses have been suggested in recent years., Material and Method: In order to examine the different diagnostic alternatives, a non-systematic search of the literature was carried out in PubMed, Embase, Current Contents, Google and relevant reference books., Results: The official cause of death was tuberculosis, but the autopsy report has never been found. Both cystic fibrosis and alpha-1-antitrypsin deficiency are possible differential diagnoses that can explain his symptoms., Interpretation: In spite of a disabling disease, Chopin was musically creative right to the end of his life. His suffering must have influenced his musical expression, which is characterised by intimacy and sentimentality. It is unlikely that we will ever find the true cause of death.

Introduction Trismus, or limited mouth opening, is a well-known complication of head and neck cancer and its treatment. It may be caused by tumour infiltration into the masticatory muscles or by treatment like surgery and radiotherapy. A limited mouth opening may have a negative effect on nutrition, phonation, dental hygiene and treatment, and quality of life. The severity of this complication depends on the location of the tumour, the type of reconstruction, the total radiation dose, fractionation, and treatment techniques. If there is no intervention, these changes may be progressive and persist for life. There are no specific treatments for trismus. Current strategies emphasize prevention and, in instances of existing trismus, collaboration between health care professionals to establish pain control, prevent the progression of trismus, and restore function. The prevalence of trismus in head and neck cancer patients ranges from 5% to 38%. Despite numerous studies, reliable data on the aetiology of trismus and appropriate treatment for it are scarce. Case report We describe a patient with squamous cell carcinoma of the oropharynx who developed trismus after surgery and radiotherapy. A multidisciplinary treatment strategy including analgesics, regional blocks, hyperbaric oxygenation therapy, external dynamic bite opener and physiotherapy, increased the mouth opening from 5 mm to 22 mm, however, the patient still suffered from xerostomia and had problems with intake of solid food. Material and methods A systematic literature search (starting January 1., 1980, and ending June 1., 2009) was performed to identify evidence-based interventions for the treatment of trismus in head and neck cancer patients. A total of 244 articles were identified from the databases. Of these, eight were excluded because of the absence of an English abstract and 214 were excluded because they were of marginal relevance to the inclusion criteria. The remaining 22 articles were evaluated independently by two experts using the Scottish Inter-collegiate Guidelines Network criteria for quality and evidence. Results There were few studies of good methodological quality on this topic. Two systematic reviews and two RCTs were identified. The other reports involved cohorts, case series, and expert opinions. Discussion Evidence in the form of clinical studies on therapeutic interventions is scarce. Numerous pharmacological treatment modalities have been described, but few are supported by the results of comparative trials involving control groups. Few studies have documented therapeutic effects for longer than a year. Better evidence was found for non-pharmacological methods, especially for physical therapy with passive and active stretching exercises, an important first-line strategy. The interincisal distance criterion for trismus varies between authors from 15 to 40 mm, which renders comparison between studies difficult. The absence of a standardized assessment protocol may also have contributed to variation between studies. An interincisal distance of 35 mm has been proposed as a definition of trismus. Explicit and precise treatment algorithms could not be established based on the available literature. However, a coordinated multidisciplinary approach in order to estimate and understand patient dysfunction is recommended; a systematic treatment plan should result in good symptom control and patient care. Prevention of trismus is more desirable than treatment for trismus.

Background: In vitro and in vivo studies have indicated that stabilizers present in pharmaceutical-grade albumin influence the albumin-binding capacity for highly protein-bound drugs. However, the half-life of the stabilizers and the quantitative effect have been difficult to determine., Method: A randomized crossover study including six healthy volunteers was performed. The study subjects received 750 mg of oral naproxen 2 h before the study. They were randomized to receive either 100 ml of 20% albumin or 100 ml of Ringer's acetate solution intravenously. Frequent blood samples were obtained. The experiment was repeated 4 weeks later with the alternate solution. The serum samples were analysed to determine the concentrations of albumin, N-acetyl-DL-tryptophan, caprylate, and naproxen., Results: The free fraction of naproxen increased significantly after the infusion of albumin (P<0.05). The increase was concurrent with the appearance of N-acetyl-DL-tryptophan and caprylate in serum. The free fraction of naproxen declined rapidly after the albumin infusion was completed. N-acetyl-DL-tryptophan had a half-life of approximately 30 min. The half-life of caprylate was <15 min., Conclusion: A transfusion of albumin results in an increase in the free fraction of naproxen. The transient increase in free-fraction naproxen decreased together with the detectable levels of the stabilizers N-acetyl-DL-tryptophan and caprylate. N-acetyl-DL-tryptophan and caprylate have a short half-life in serum.

Background: Nurses at The Norwegian Radium Hospital have reported that some patients notice an unpleasant smell or taste in accordance with flushing of intravenous lines with commercially available prefilled syringes. We have conducted a study in healthy volunteers to investigate the occurrence, consistency and intensity of this phenomenon., Methods: A randomised, blinded, crossover study comparing commercial available prefilled saline 9 mg/ml syringes to saline 9 mg/ml for injection in polyethylene package was performed in 10 healthy volunteers. The volunteers were given intravenous injections of varying volume and speed. Data were analysed using descriptive statistics, and also Wilcoxon Signed Rank Test to compare groups., Results: After intravenous injection, 2 of 15 recordings demonstrated any sensation of smell or taste after injection of saline from polyethylene package, while 14 of 15 recordings noted a sensation after injection of saline from prefilled syringes. The intensity of the unpleasant sensation was rated significantly higher after injection of saline from prefilled syringes compared to saline from polyethylene (p = 0.001)., Conclusions: Injection of saline from prefilled syringes in healthy volunteers resulted in an experience of bad taste or smell. It is important that nurses and health workers are aware of the phenomenon as described in this article in order to choose the preferred product for a given patient.

Background: Pelvic radiation therapy is an important element of curative therapy for gynaecological cancers. Serious radiation-related complications developing months or years after treatment are known as late radiation tissue injury (LRTI)., Methods: We investigated the possible pain reducing effect of hyperbaric oxygen treatment (HBOT) in a study of 16 patients with LRTI after radiation for gynaecological malignancy. The 16 patients were registered prospectively, underwent HBOT for 21 consecutive days and were followed for a 6-month period after treatment using the Brief Pain Inventory, Montgomery and Aasberg Depression Rating Scale, as well as registration of global patient scores, analgesic consumption and magnetic resonance imaging (MRI) findings., Results: HBOT was shown to have insignificant effect on pain, pain characteristics, daily function, the use of analgesics and MRI-related tissue injury. Fifty percent of the patients still reported some or good effect of the treatment., Conclusion: It is not possible to conclude from our study if gynaecological patients with pelvic pain will benefit from HBOT. The application of HBOT to selected patients may be justified, but further research with adequate sample size, as well as the timing of HBOT related to the development of LRTI, is required to establish the optimum patient selection.

Verbal descriptions of pain contribute to the understanding of a patient's pain experience. The aim of this study was to identify typical pain descriptors used by Norwegian cancer patients and the possible relationships among these verbal descriptors, pain intensity, and quality of pain. A one-day prevalence study targeting hospitalized cancer patients in Norway was performed. A questionnaire based on the Brief Pain Inventory was used, and additional information regarding pain descriptors and changes in skin sensibility was included. Of the 453 included patients, 97% managed to describe their pain with one of the 12 descriptors available. "Aching" was the single most frequently used descriptor (n=271). Of these patients, 201 reported altered skin sensibility in the area of pain. The descriptor "piercing" and the number of descriptors used by each patient were significantly related to high pain intensity. No clear clustering was found between the descriptors, but typical neuropathic descriptors were significantly correlated with altered skin sensibility. The findings suggest that Norwegian cancer patients effortlessly use several pain descriptors, and "aching" is most frequently used. Although the verbal descriptors provide valuable information regarding the pain experience, it is not possible to differentiate pain mechanisms simply based on pain descriptors.

Randomized controlled trials provide the best evidence for the safety and effectiveness of interventions. However, the reliance on this study design as the only criterion for credible evidence is not possible in all areas of palliative medicine. Although we must exercise caution in making definitive claims from uncontrolled trial data, limitations in performing controlled trials should neither preclude the use of findings from well-designed nonrandomized controlled trials nor, more importantly, deprive patients of potentially effective treatments.

Background: Several countries use drugs containing cannabinoids for symptom management in patients that need palliative treatment., Material and Method: Articles were retrieved through a literature search for randomized controlled studies of cannabinoids used to treat cancer-related symptoms such as pain, nausea and appetite., Results: Evidence for clinical effect is limited. Some randomized studies have shown a treatment effect of cannabinoids in neuropathic pain. Cannabinoid-containing drugs can have a moderate anti-emetic effect and can stimulate appetite in some subgroups of patients., Interpretation: Many questions about clinical efficacy and side effects have still not been answered for cannabinoid-containing drugs and there is not sufficient evidence available from relevant randomised controlled trials to base a decision on whether or not to permit such drugs in palliative care in Norway. It is however likely that drugs containing cannabinoids can help to control certain symptoms in some patients.

Background: In vitro studies have indicated that stabilizers present in pharmaceutical-grade albumin influence albumin-binding capacity for highly protein bound drugs., Methods: A randomized study including 40 surgical patients, treated with either albumin or starch solutions, was performed. Volumes of colloids were given based on clinical indication. Blood samples were obtained. The serum samples were analyzed to determine the concentrations of albumin, tryptophan, N-acetyl-dl-tryptophan, caprylate and alpha-1-acid glycoprotein as well as in vitro drug binding of naproxen, warfarin and digitoxin., Results: During surgery, the albumin concentration declined in the Starch group from 26.8 to 15.3 g/l. It remained unchanged in the Albumin group (29.2 g/l). The two groups were analyzed with the pre-operative sample acting as the control. In the starch group, the percent free concentration of the drugs increased significantly (P<0.01): for naproxen from 0.2% to 0.6%, for warfarin from 1.2% to 1.8% and for digitoxin from 6.8% to 11.1%. In the Albumin group, the % free fraction of naproxen doubled from 0.1% to 0.2% (P<0.05), whereas the % free fraction of warfarin decreased from 1.1% to 1.0% (P<0.05). The free fraction of digitoxin remained unchanged., Conclusions: Infusion of albumin during surgery resulted in maintained albumin values and almost maintained binding parameters for the study drugs, although some statistically significant changes were found. The use of starch solutions, however, led to in a reduction in albumin values and a significant reduction in binding parameters.

Age distribution in developed countries is currently shifting towards older age. However, knowledge regarding diseases and treatment of the oldest patients remains incomplete, especially when it comes to acute and chronic pain. Pain assessment is complicated in these patients as they often have more than one diagnosis contributing to the clinical picture, in addition age-related changes in pain perception and cognitive impairment render evaluation of subjective symptoms difficult. Multidisciplinary pain management programmes that combine pharmacologic and non-pharmacologic treatment have proven efficacious in elderly patients. The choice of analgesics demands an understanding of age-related changes in drug-metabolism, co-morbidity and concurrent medication. Adjustment of drug doses and evaluation of benefits and risks should be tailored to each individual. There is an urgent need for better professional education programmes and further dedicated research specifically targeted to the needs of the elderly in our community.

Purpose: Pain severely impairs health-related quality of life and is a feared symptom among cancer patients. Unfortunately, patients often do not receive optimal care. We wanted to evaluate the quality of cancer pain treatment in Norwegian hospitals., Patients and Methods: A one-day prevalence study targeting hospitalised cancer patients above 18 years of age was performed. A questionnaire based on the Brief Pain Inventory was used, and additional information regarding sex, age, diagnosis, break through pain (BTP), and treatment was included., Results: Fifty two percent of the included patients stated having cancer related pain (n=453), and mean pain during the previous 24 hours for these patients was NRS 3.99 (Numeric Rating scale 1-10). Presence of metastasis, occurrence of BTP, and abnormal skin sensibility in the area of pain were associated with higher pain scores. Forty two percent of all patients used opioids. However, these patients still had higher pain scores, more episodes of BTP, and more influence of the pain on daily life functions than average. Thirty percent of patients with severe pain (NRS>or=5) did not use opioids, and some of these patients did not receive any analgesics at all., Conclusion: Although most cancer patients receive an acceptable pain treatment in Norwegian hospitals, there are patients who are not adequately managed. Lack of basic knowledge and individual systematic symptom assessment may be reasons for the underuse of analgesics and the resulting unnecessary suffering among the cancer patients.

Background: Substance abuse in pain management can undermine treatment compliance, the effectiveness of therapies, and social support and functioning., Material: An overview is given regarding pain management for patients on chronic use of opioids and for patients with drug dependence and substance abuse., Results: Clinical experience as well as relevant documentation demonstrates that management of these patients remains one of the most challenging problems in clinical medicine., Conclusion: Assessment and treatment plans for this patient group require an understanding of tolerance, physical dependence and drug abuse. It is imperative that the patient's ongoing treatment is planned in a multidisciplinary setting, so as to assure a consistent, structured and shared approach by all caregivers.

Breakthrough pain or transient worsening of pain in patients with an ongoing steady pain is a well known feature in cancer pain patients, but it is also seen in non-malignant pain conditions with involvement of nerves, muscles, bones or viscera. Continuous and intermittent pain seems to be a general feature of these different pain conditions, and this raises the possibility of one or several common mechanisms underlying breakthrough pain in malignant and non-malignant disorders. Although the mechanisms of spontaneous ongoing pain and intermittent flares of pain (BTP) may be difficult to separate, we suggest that peripheral and/or central sensitization (hyperexcitability) may play a major role in many causes of BTP. Mechanical stimuli (e.g. micro-fractures) changes in chemical environments and release of tumour growth factors may initiate sensitization both peripherally and centrally. It is suggested that sensitization could be the common denominator of BTP in malignant and non-malignant pain.

Background: In spite of increased knowledge in palliative care, there are still cancer patients who do not receive adequate pain relief. There is limited information on cancer pain experience in Norwegian hospitals. More data is needed in order to understand why barriers still exist to adequate pain management., Material and Methods: We performed a one-day prevalence study of cancer pain in all hospitalized patients in the southern health region of Norway. A questionnaire based on the Brief Pain Inventory was used., Results: 309 patients were included. 40% used no analgesics. 51 % reported having pain while hospitalized; mean pain level on the visual analogue scale over the last 24 hours was 2.6. 70 patients reported strong to intolerable pain (visual analogue scale > or = 5), and 27 of these patients did not use opioids. 104 patients reported symptoms consistent with neuropathic pain, but only 7 used relevant co-analgesics. 102 patients reported break-through pain. Patients with neuropathic pain and break-through pain scored significantly higher on pain and significantly worse on all global variables like quality of sleep, daily activity, and ability to work., Interpretation: Many cancer patients still have pain, possibly because of inadequate medication. Key words for improvement are better knowledge, higher professional awareness, and systematic symptom assessment and pain analysis.

Background: Blood transfusions can be lifesaving, but definite transfusion triggers for different clinical situations need to be determined., Material and Methods: We carried out a survey among Norwegian anaesthesiologists regarding haemoglobin levels and transfusion triggers during surgery and in an intensive care setting. Blood conservation techniques were also explored. The results for surgical patients were compared with those from a similar survey in 1996., Results: Compared with 1996, Norwegian anaesthesiologists now accept significantly lower transfusion triggers for surgical patients. Acceptable haemoglobin levels varied in the different patient examples in both the surgical and intensive care groups. With regard to surgery, junior doctors accept a lower transfusion trigger than do senior anaesthesiologists. A more liberal transfusion strategy is apparently used in patients with coronary disease., Interpretation: Norwegian anaesthesiologists have changed their attitude to acceptable transfusion triggers over the 1996-2002 period. In an intensive care setting, they appear to have a more liberal transfusion policy compared to anaesthesiologists in other western European countries.

Background: Albumin is the most abundant protein in blood plasma, and due to its ligand binding properties, serves as a circulating depot for endogenous and exogenous (e.g. drugs) compounds. Hence, the unbound drug is the pharmacologically active drug. Commercial human albumin preparations are frequently used during surgery and in critically ill patients. Recent studies have indicated that the use of pharmaceutical-grade albumin is controversial in critically ill patients. In this in vitro study we investigated the drug binding properties of pharmaceutical-grade albumins (Baxter/Immuno, Octapharma, and Pharmacia & Upjohn), native human serum, and commercially available human serum albumin from Sigma Chemical Company., Methods: The binding properties of the various albumin solutions were tested in vitro by means of ultrafiltration. Naproxen, warfarin, and digitoxin were used as ligands. HPLC was used to quantitate the total and free drug concentrations. The data were fitted to a model of two classes of binding sites for naproxen and warfarin and one class for digitoxin, using Microsoft Excel and Graphpad Prism., Results: The drugs were highly bound to albumin (95-99.5%). The highest affinity (lowest K1) was found with naproxen. Pharmaceutical-grade albumin solutions displayed significantly lower drug-binding capacity compared to native human serum and Sigma albumin. Thus, the free fraction was considerably higher, approximately 40 times for naproxen and 5 and 2 times for warfarin and digitoxin, respectively. The stabilizers caprylic acid and N-acetyl-DL-tryptophan used in the manufacturing procedure seem to be of importance. Adding the stabilizers to human serum and Sigma albumin reduced the binding affinity whereas charcoal treatment of the pharmaceutical-grade albumin from Octapharma almost restored the specific binding capacity., Conclusion: This in vitro study demonstrates that the specific binding for warfarin and digitoxin is significantly reduced and for naproxen no longer detectable in pharmaceutical-grade albumin. It further shows that the addition of stabilizers may be of major importance for this effect.

Background: Patients with advanced cancer may present complex sets of symptoms, of which pain is the most prevalent. In addition to systemic pharmacological therapy for pain management, neurolytic blocks are also effective in controlling cancer pain in selected patients., Method: Various neurolytic blocks used in the treatment of cancer pain are reviewed., Results: Several studies have documented the efficacy of neurolytic blocks in reducing pain intensity and opioid consumption, although good prospective, randomized controlled trials are scarce. The narrow risk-benefit ratio associated with neurolysis techniques requires knowledge of the complications associated with the different neurolytic blocks in order to minimise undesirable effects., Interpretation: Interventional techniques continue to play an important role in the management of cancer pain. The quality of the neurolytic blocks improves when they are performed image-guided in collaboration with an interventional radiologist. These blocks should never be considered an isolated treatment, but as a component of a comprehensive therapeutic strategy.