Preoperative hypoalbuminaemia in liver surgery: an observational study at a university medical centre.

OBJECTIVES: Preoperative hypoalbuminaemia is associated with adverse outcome, including increased postoperative mortality in cardiovascular surgery, neurosurgery, trauma and orthopaedic surgery. However, much less is known about the association between preoperative serum albumin and clinical outcomes after liver surgery. In this study, we sought to determine whether hypoalbuminaemia before partial hepatectomy is associated with a worse postoperative outcome. DESIGN: Observational study. SETTING: University Medical Centre in Germany. PARTICIPANTS: We analysed 154 patients enrolled in the perioperative PHYsostigmine prophylaxis for liver resection patients at risk for DELIrium and postOperative cognitive dysfunction (PHYDELIO) trial with a preoperative serum albumin assessment. Hypoalbuminaemia was defined as serum albumin <35 g/L. Subgroups classified as hypoalbuminaemia and non-hypoalbuminaemia consisted of 32 (20.8%) and 122 (79.2%) patients, respectively. OUTCOME MEASURES: The outcome parameters of interest were postoperative complications according to Clavien (moderate: I, II; major: ≥III), length of intensive care unit (ICU) stay, length of hospital stay and survival rates 1 year after surgery. RESULTS: Preoperative hypoalbuminaemia was associated with the occurrence of major postoperative complications (OR 3.051 (95% CI 1.197 to 7.775); p=0.019) after adjusting for age, sex, randomisation, American Society of Anesthesiologists physical status, preoperative diagnosis and Child-Pugh class. Both ICU and hospital lengths of stay were significantly prolonged in patients with preoperative hypoalbuminaemia (OR 2.573 (95% CI 1.015 to 6.524); p=0.047 and OR 1.296 (95% CI 0.254 to 3.009); p=0.012, respectively). One-year survival was comparable between patients with and without hypoalbuminaemia. CONCLUSIONS: We found that low serum albumin before surgery was associated with a worse short-term outcome after partial hepatectomy, which strengthens the prognostic value of serum albumin in the setting of liver surgery. TRIAL REGISTRATION NUMBERS: ISRCTN18978802 and EudraCT 2008-007237-47.

Self-Reported Practices and Emotions in Prescribing Opioids for Chronic Noncancer Pain: A Cross-Sectional Study of German Physicians.

Background: The pressure on physicians when a patient seeks pain relief and their own desire to be self-effective may lead to the prescription of strong opioids for chronic noncancer pain (CNCP). This study, via physician self-reporting, aims to identify and measure (i) physician adherence to national opioid prescribing guidelines and (ii) physician emotions when a patient seeks a dosage increase of the opioid. Methods: Within a cross-sectional survey­conducted as part of a randomized controlled online intervention trial (ERONA)­600 German physicians were queried on their opioid prescribing behavior (choice and formulation of opioid, indications) for CNCP patients and their emotions to a case vignette describing a patient seeking an opioid dosage increase without signs of objective deterioration. Results: The prescription of strong opioids in this study was not always in accordance with current guidelines. When presented with a scenario in which a patient sought to have their opioid dose increased, some physicians reported negative feelings, such as either pressure (25%), helplessness (25%), anger (23%) or a combination. The risk of non-guideline-compliant prescribing behavior using the example of ultrafast-acting fentanyl for CNCP was increased when negative emotions were present (OR: 1.7; 95%-CI: 1.2−2.6; p = 0.007) or when sublingual buprenorphine was prescribed (OR: 15.4; 95%-CI: 10.1−23.3; p < 0.001). Conclusions: Physicians' emotional self-awareness represents the first step to identify such direct reactions to patient requests and to ensure a responsible, guideline-based opioid prescription approach for the long-term well-being of the patient.

The role of simulated-experience and descriptive formats on perceiving risks of strong opioids: A randomized controlled trial with chronic noncancer pain patients.

OBJECTIVES: Opioid prescription rates worldwide suggest miscalibrated risk perceptions among those who prescribe, dispense, and take opioids. Findings from cognitive science show that risk perceptions can differ systematically depending on whether people learn about risks by description or experience. We investigated the effects of descriptive and simulated experience risk formats on patients' risk perceptions and behavior regarding long-term strong opioid use. METHODS: 300 German patients with chronic noncancer pain were randomly assigned in an exploratory randomized controlled trial to either a descriptive format (fact box) or a simulated experience format (interactive simulation). Primary endpoints were subjective and objective risk perceptions and intended intake behavior. RESULTS: Both formats significantly improved patients' objective risk perception; patients who saw the fact box estimated some outcomes more accurately (p = .031). Formats were equally effective in improving patients' subjective risk perception in terms of opioids' harms; however, patients receiving the simulation showed a greater reduction and termination of their opioid intake (p = .030) and a higher uptake of alternative therapies. CONCLUSIONS: Descriptive and simulated experience risk formats improve risk perceptions and behavior regarding potent but highly risky drugs. PRACTICE IMPLICATIONS: To eliminate risky behavior, simulated experience formats may be superior to descriptive formats.

Efficacy and safety of strong opioids for chronic noncancer pain and chronic low back pain: a systematic review and meta-analyses.

ABSTRACT: In recent years, long-term prescribing and use of strong opioids for chronic noncancer pain (CNCP) has increased in high-income countries. Yet existing uncertainties, controversies, and differing recommendations make the rationale for prolonged opioid use in CNCP unclear. This systematic review and meta-analyses compared the efficacy, safety, and tolerability of strong opioids with placebo or nonopioid therapy in CNCP, with a special focus on chronic low back pain (CLBP). Systematic literature searches were performed in 4 electronic databases (MEDLINE, Web of Science, Cochrane Library, and CINAHL) in July 2019 and updated by regular alerts until December 2020. We included 16 placebo-controlled randomized controlled trials for CLBP and 5 studies (2 randomized controlled trials and 3 nonrandomized studies) of opioids vs nonopioids for CNCP in the quantitative and qualitative synthesis. Random effects pairwise meta-analyses were performed for efficacy, safety, and tolerability outcomes and subgroup analyses for treatment duration, study design, and opioid experience status. Very low to low certainty findings suggest that 4 to 15 weeks (short or intermediate term) opioid therapy in CLBP (compared with placebo) may cause clinically relevant reductions in pain but also more gastrointestinal and nervous system adverse events, with likely no effect on disability. By contrast, long-term opioid therapy (≥6 months) in CNCP may not be superior to nonopioids in improving pain or disability or pain-related function but seems to be associated with more adverse events, opioid abuse or dependence, and possibly an increase in all-cause mortality. Our findings also underline the importance and need for well-designed trials assessing long-term efficacy and safety of opioids for CNCP and CLBP.

Patients' self-reported physical and psychological effects of opioid use in chronic noncancer pain-A retrospective cross-sectional analysis.

BACKGROUND: Strong opioids can have unintended effects. Clinical studies of strong opioids mainly report physical side effects, psychiatric or opioid use disorders. To date, too little attention has been paid to the psychological effects of opioids to treat patients with chronic noncancer pain (CNCP). This study aims to identify and measure (i) the nature and frequency of physical and psychological effects and (ii) the degree of physician counseling of patients with CNCP taking strong opioids. METHODS: Within a cross-sectional survey-conducted as part of a randomised controlled online intervention trial (ERONA [Experiencing the risk of overusing opioids among patients with chronic non-cancer pain in ambulatory care])-300 German CNCP patients were surveyed via patient-reported outcome measures regarding on both the side effects from their use of strong opioids as well as their counselling experience. RESULTS: Among the patients' reported effects, the psychological outcomes of the opioids in CNCP were: feeling relaxed (84%), fatigue (76%), dizziness (57%), listlessness (37%), difficulty with mental activities (23%), dulled emotions (17%) and poor memory (17%). Ninety-two per cent of the patients reported having received information about opioid effects, and 46% had discussed cessation of the opioid medication with their physicians before commencing the prescription. CONCLUSIONS: In addition to the well-known physical side effects, patients with CNCP taking strong opioids experience significant psychological effects. In view of these effects, discontinuation of opioid therapy should be discussed early to ensure their benefits do not outweigh their harm. SIGNIFICANCE: In this study, patients with non-cancer pain notice that opioids they have taken do not only cause physical side effects but also may have an impact on their psyche and their emotions and, thus, may also affect quality of life substantially. Clinical trial number: DRKS00020358.

Educating Pharmacists on the Risks of Strong Opioids With Descriptive and Simulated Experience Risk Formats: A Randomized Controlled Trial.

Objectives. High opioid prescription rates in the United States and Europe suggest miscalibrated risk perceptions among those who prescribe, dispense, and take opioids. Findings from cognitive decision science suggest that risk perceptions and behaviors can differ depending on whether people learn about risks by experience or description. This study investigated effects of a descriptive versus an experience-based risk education format on pharmacists' risk perceptions and counseling behavior in the long-term administration of strong opioids to patients with chronic noncancer pain. Methods. In an exploratory, randomized controlled online trial, 300 German pharmacists were randomly assigned to either a descriptive format (fact box) or a simulated experience format (interactive simulation). Primary Outcome Measures. 1) Objective risk perception, 2) subjective risk perception, and 3) intended and 4) actual counseling behavior. Results. Both risk formats significantly improved pharmacists' objective risk perception, but pharmacists exposed to the fact box estimated the benefit-harm ratio more accurately than those exposed to the simulation. Both formats proved equally effective in adjusting pharmacists' subjective risk perception toward a better recognition of opioids' harms; however, pharmacists receiving the simulation showed a greater change in their actual counseling behavior and higher consistency between their intended and actual counseling than pharmacists receiving the fact box. Conclusion. The simulated experience format was less effective than the descriptive format in improving pharmacists' objective risk perception, equally effective in motivating pharmacists to counsel patients on less risky treatment alternatives and more effective in changing the reported actual counseling behavior. Implications. These exploratory findings provide important insights into the relevance of the description-experience gap for drug safety and raise questions for future research regarding the specific mechanisms at work.

Experiencing the risk of overutilising opioids among patients with chronic non-cancer pain in ambulatory care (ERONA): the protocol of an exploratory, randomised controlled trial.

INTRODUCTION: The US opioid crisis and increasing prescription rates in Europe suggest inappropriate risk perceptions and behaviours of people who prescribe, take or advise on opioids: physicians, patients and pharmacists. Findings from cognitive and decision science in areas other than drug safety suggest that people's risk perception and behaviour can differ depending on whether they learnt about a risk through personal experience or description. Experiencing the risk of overutilising opioids among patients with chronic non-cancer pain in ambulatory care (ERONA) is the first-ever conducted trial that aims at investigating the effects of these two modes of learning on individuals' risk perception and behaviour in the long-term administration of WHO-III opioids in chronic non-cancer pain. METHODS AND ANALYSIS: ERONA-an exploratory, randomised controlled online survey intervention trial with two parallel arms-will examine the opioid-associated risk perception and behaviour of four groups involved in the long-term administration of WHO-III opioids: (1) family physicians, (2) physicians specialised in pain therapy, (3) patients with chronic (≥3 months) non-cancer pain and (4) pharmacists who regularly dispense narcotic substances. Participants will be randomly assigned to one of two online risk education interventions, description based or experiencebased. Both interventions will present the best medical evidence available. Participants will be queried at baseline and after intervention on their risk perception of opioids' benefit-harm ratio, their medical risk literacy and their current/intended risk behaviour (in terms of prescribing, taking or counselling, depending on study group). A follow-up will occur after 9 months, when participants will be queried on their actual risk behaviour. The study was developed by the authors and will be conducted by the market research institution IPSOS Health. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board of the Max Planck Institute for Human Development. Results will be disseminated through peer-reviewed journals, conference presentations and social media. TRIAL REGISTRATION NUMBER: DRKS00020358.

Epidural Anesthesia in Liver Surgery-A Propensity Score-Matched Analysis.

OBJECTIVE: To assess the effects of epidural anesthesia (EA) on patients who underwent liver resection. DESIGN: Secondary analysis of a prospective randomized controlled trial. SETTING: This single-center study was conducted at an academic medical center. METHODS: A subset of 110 1:1 propensity score-matched patients who underwent liver resection with and without EA were analyzed. Outcome measures were pain intensity ≥5 on a numeric rating scale (NRS) at rest and during movement on postoperative days 1-5, analyzed with logistic mixed-effects models, and postoperative complications according to the Clavien-Dindo classification, length of hospital stay (LOS), and one-year survival. One-year survival in the matched cohorts was compared using a frailty model. RESULTS: EA patients were less likely to experience NRS ≥5 at rest (odds ratio = 0.06, 95% confidence interval [CI] = 0.01 to 0.28, P < 0.001). These findings were independent of age, sex, Charlson comorbidity index, baseline NRS, and surgical approach (open vs laparoscopic). The number and severity of postoperative complications and LOS were comparable between groups (P = 0.258, P > 0.999, and P = 0.467, respectively). Reduced mortality rates were seen in the EA group one year after surgery (9.1% vs 30.9%, hazard ratio = 0.32, 95% CI = 0.11 to 0.90, P = 0.031). No EA-related adverse events occurred. Earlier recovery of bowel function was seen in EA patients. CONCLUSIONS: Patients with EA had better postoperative pain control and required fewer systemic opioids. Postoperative complications and LOS did not differ, although one-year survival was significantly improved in patients with EA. EA applied in liver surgery was effective and safe.

A calcium-containing electrolyte-balanced hydroxyethyl starch (HES) solution is associated with higher factor VIII activity than is a non-balanced HES solution, but does not affect von Willebrand factor function or thromboelastometric measurements--results of a model of in vitro haemodilution.

BACKGROUND: Hydroxyethyl starch (HES) is known to impair blood coagulation. The impact of calcium-containing, balanced carrier solutions of HES on coagulation is controversial. We investigated the effects of increasing degrees of haemodilution with modern 6%, electrolyte-balanced HES vs non-balanced HES on coagulation in vitro, and compared the balanced HES to a balanced crystalloid solution for an internal control. MATERIALS AND METHODS: Blood samples from ten healthy volunteers were diluted in vitro by 20%, 40% and 60% with either calcium-containing balanced 130/0.42 HES, non-balanced 130/0.4 HES or balanced crystalloid. In all samples, blood counts, prothrombin time ratio, activated partial thromboplastin time, ionized calcium, factor VIII activity, von Willebrand factor antigen, von Willebrand factor collagen binding activity, and von Willebrand factor activity were determined, and activated rotational thromboelastometry (EXTEM and FIBTEM assays) was performed. RESULTS: Haemodilution impaired coagulation in a dilution-dependent manner as determined by both conventional laboratory assays and thromboelastometry. Ionized calcium increased with balanced HES (p≤0.004), but decreased with non-balanced HES (p≤0.004). Prothrombin time ratio (p≤0.002) and factor VIII levels (p=0.001) were better preserved with balanced HES than with non-balanced HES in dilutions ≥40%. Thromboelastometry showed no differences between values in blood diluted with the balanced or non-balanced HES. DISCUSSION: In vitro, a balanced calcium-containing carrier solution of 6% HES 130/0.42 preserved coagulation better than did non-balanced HES 130/0.4 as quantified by conventional coagulation assays, but not in activated thromboelastometry. One explanation could be the increased ionized calcium levels after dilution with calcium-containing carrier solutions.

Referral practices in patients suffering from non-malignant chronic pain.

This paper presents the results of a prospective observational cohort study investigating referral practices to six specialized pain centres (SPCs) in 303 patients with headache (HD), low back pain (LBP), and neuropathic pain (NP). The study was divided into three parts. Part 1: The pain health care history (contacts with general practitioners and specialists, further referrals, time spans, therapies) before first contact with the SPC. Part 2: Reality of pain therapy and management in the SPC (patients' attrition, interdisciplinarity of therapy and novel therapeutic strategies instigated). Part 3: Follow-up and assessment of pain levels (NRS, SES), disability scores (PDI), QoL scores (SF 12), and anxiety and depression scores (HADS) at 0, 6 and 12 months. Using an ordinal linear regression model, factors predicting a good treatment outcome were identified. On average it took 3 years of pain symptoms before first consultation with GP. The median time period from the first pain sensations until the appointment in the SPC was 12 years. Nearly half of the referrals to specialists or SPCs were initiated by a non-professional. In the SPC the medication was changed in 71% of cases. Care was interdisciplinary in only 32%. At 6 and 12 months after the first contact with the SPC, only 20% of the patients had improved with respect to levels of pain and psychometric data. A high degree of chronicity, a history of pain-associated surgeries and low social support were negative predictors for treatment outcome.

Comparing methodological quality and consistency of international guidelines for the management of patients with chronic heart failure.

BACKGROUND: Guidelines (GLs) for the management of heart failure (HF) are of great importance in order to define and disseminate therapeutic recommendations based on scientific evidence. The aim was to analyse and to compare the methodological quality of HF GLs as well as to evaluate the consistency of therapeutic recommendations. METHODS: Eleven international GLs for the management of chronic HF were identified by search of the internet, electronic databases and references of published literature. Their methodological quality was assessed by two different appraisal instruments: (1) according to the US National Guideline Clearinghouse (NGC) on a scale from 0 to 17 points, (2) according to the German Guideline Clearinghouse (Agency for Quality in Medicine, AQUMED) on a scale from 0 to 44 points. Clinical criteria for assessment of the consistency of the recommendations included diagnostic testing, pharmacological and non-pharmacological treatment. RESULTS: The quality scores of the GLs varied substantially with a range of 1.5-15.5 points (NGC) and 8-30 points (AQUMED). The greatest variation was found in the dimensions "development" and "evidence". Only 3 of the 11 GLs (approximately 30%) were rated as methodologically well prepared. The recommendations on diagnostic procedures and medical management were rather consistent among the different GLs. CONCLUSIONS: Published international GL recommendations on medical management of patients with chronic HF are broadly consistent. The methodological quality of the GLs, however, varies to a great extent. Improvement is needed in most methodological aspects, especially in the dimensions "evidence" and "applicability".