Does opioid therapy enhance quality of life in patients suffering from chronic non-malignant pain? A systematic review and meta-analysis.

Background and objective: Chronic pain is associated with a poor health-related quality of life (HRQL). Whereas the prescription rate of opioids increased during the last decades, their use in chronic non-malignant pain remains unclear. However, there is currently no clinical consensus or evidence-based guidelines that consider the long-term effects of opioid therapy on HRQL in patients with chronic non-cancer pain. This systematic review aims to address the question of whether opioid therapy improves HRQL in patients with chronic non-malignant pain and provide some guidance to practitioners. Databases and data treatment: PubMed, EMBASE and CENTRAL were searched in June 2020 for double-blind, randomized trials (RCTs), comparing opioid therapy to placebo and assessed a HRQL questionnaire. The review comprises a qualitative vote counting approach and a meta-analysis of the Short Form Health Survey (SF-36), EQ-5D questionnaire and the pain interference scale of the Brief pain inventory (BPI). Results: 35 RCTs were included, of which the majority reported a positive effect of opioids for the EQ-5D, the BPI and the physical component score (PCS) of the SF-36 compared to placebo. The meta-analysis of the PCS showed a mean difference of 1.82 [confidence interval: 1.32, 2.32], the meta-analysis of the EQ-5D proved a significant advantage of 0.06 [0.00, 0.12]. In the qualitative analysis of the mental component score (MCS) of the SF-36, no positive or negative trend was seen. No significant differences were seen in the MCS (MD: 0.65 [-0.43, 1.73]). A slightly higher premature dropout rate was found in the opioid group (risk difference: 0.04 [0.00, 0.07], p = .07). The body of evidence is graded as low to medium. Conclusion: Opioids have a statistically significant, but small and clinical not relevant effect on the physical dimensions of HRQL, whereas there is no effect on mental dimensions of HRQL in patients with chronic non-malignant pain during the initial months of treatment. In clinical practice, opioid prescriptions for chronic non-cancer pain should be individually assessed as their broad efficacy in improving quality of life is not confirmed. The duration of opioid treatment should be determined carefully, as this review primarily focuses on the initial months of therapy.

Equianalgesic potency ratios of opioids used in patient-controlled analgesia: A network meta-analysis.

OBJECTIVE: To determine equianalgesic potency ratios for opioids with an -evidence-based approach without the use of pre-existing potency tables. DESIGN: Frequentist network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing opioids in patient-controlled analgesia (PCA). SETTING: A systematic review. DATA SOURCES: A systematic search of MEDLINE, EMBASE, the Cochrane Library (CENTRAL), and Web of Science identified relevant RCTs from start of recording to 2019. ELIGIBILITY CRITERIA: RCTs comparing opioids via intravenous PCA in acute pain, with comparable resulting pain scores and identical treatment with coanalgesics at study level. The quality of studies was assessed using the Cochrane risk of bias tool with six items. RESULTS: 52 RCTs were identified with data for 16 opioids. Primary endpoint was the inverted ratio of means of the total consumption administered via PCA, which resembles the analgesic potency. The calculated analgesic potencies were sufentanil 423 [95 percent CI 334.99; 532.96], fentanyl 58 [48.22; 68.60], buprenorphine 37 [26.66; 50.81], remifentanil 13 [9.37; 19.13], alfentanil 7 [4.02; 11.01], hydromorphone 6 [4.96; 8.43], oxymorphone 6 [4.46; 8.84], butorphanol 4.5 [3.05; 6.73], diamorphine 2.2 [1.16; 4.10], morphine 1, oxycodone 0.9 [0.65; 1.34], piritramide 0.9 [0.55; 1.56], nalbuphine 0.7 [0.54; 0.95], pethidine 0.12 [0.10; 0.15], meptazinol 0.08 [0.03; 0.20], and tramadol 0.08 [0.07; 0.10]. CONCLUSIONS: The results in part contradict the values from the literature, which have been criticized for their imprecision. From clinical experience however, our findings seem very plausible. Short-acting opioids are less potent compared to longer acting drugs, eg, morphine, probably due to shorter intervals for -readministration.

Preoperative anxiety in adults - a cross-sectional study on specific fears and risk factors.

BACKGROUND: Preoperative anxiety comprising anesthesia and surgery related anxiety is common and perceived by many patients as the worst aspect of the surgical episode. The aim of this study was to identify independent predictors of these three anxieties dimensions and to quantify the relevance of specific fears particularly associated with anesthesia. METHODS: This study was part of a cross-sectional survey in patients scheduled to undergo elective surgery. Anxiety levels were measured with the Amsterdam Preoperative Anxiety and Information Scale (APAIS). Modified numeric rating scales (mNRS, range 0-10) were used to assess the severity of eight selected specific fears which were predominantly analyzed descriptively. Multivariate stepwise linear regression was applied to determine independent predictors of all three anxiety dimensions (APAIS anxiety subscales). RESULTS: 3087 of the 3200 enrolled patients were analyzed. Mean (SD) total preoperative anxiety (APAIS-A-T, range 4-20) was 9.9 (3.6). High anxiety (APAIS-A-T > 10) was reported by 40.5% of subjects. Mean (SD) levels of concern regarding the eight studied specific fears ranged from 3.9 (3.08) concerning "Anesthesiologist error" to 2.4 (2.29) concerning "Fatigue and drowsiness" with an average of 3.2 (2.84) concerning all specific fears. Ranking of all specific fears according to mean mNRS scores was almost identical in patients with high versus those with low anxiety. Among nine independent predictors of anxiety, only 3 variables (female gender, negative and positive anesthetic experience) independently predicted all three APAIS anxiety subscales. Other variables had a selective impact on one or two APAIS anxiety subscales only. Female gender had the strongest impact on all three APAIS anxiety subscales. Adjusted r2 values of the three models were all below 13%. CONCLUSIONS: The high variability of importance assigned to all specific fears suggests an individualized approach is advisable when support of anxious patients is intended. Considering independent predictors of anxiety to estimate each patient's anxiety level is of limited use given the very low predictive capacity of all three models. The clinical benefit of dividing patients into those with high and low anxiety is questionable. TRIAL REGISTRATION: German Registry of Clinical Trials (DRKS00016725), retrospectively registered.

An overview of intravenous amisulpride as a new therapeutic option for the prophylaxis and treatment of postoperative nausea and vomiting.

Introduction: Current therapies of postoperative nausea and vomiting (PONV) are based on a combination of antiemetics from different pharmacological classes. Dopamine receptor antagonists are one of the cornerstones of such multimodal antiemetic approach, with droperidol being the best studied representative of this group. Droperidol's use has significantly declined after the FDA's black-box warning in 2001 due to its QT-prolonging properties. Amisulpride is a promising antiemetic agent which could fill this gap.Areas covered: In this review, the authors discuss the pharmacological profile as well as clinical safety and efficacy of intravenous amisulpride and its relevance in the management of PONV. The article is based on a Medline, ClinicalTrials.gov, and Cochrane Library search for studies on amisulpride conducted so far.Expert opinion: Promising clinical results on Barhemsys®, an intravenous formulation of amisulpride, make it a potential future drug of choice from the dopamine receptor antagonist group, replacing droperidol after its safety concerns. Amisulpride's success on the market will mostly be determined by its cost-effectiveness and it will likely find a brighter use on the US-market, where the black-box warning led to droperidol's withdrawal, while in many European countries, droperidol is still being used as an antiemetic.

Progress of intracranial pressure and cerebral perfusion pressure in patients during the development of brain death.

BACKGROUND: Clinical investigations of brain death are supposed to prove absence of cerebral perfusion. However, only limited data are available documenting intracranial pressure (ICP) and cerebral perfusion pressure (CPP) during the development of brain death. Our study presents additional data to understand the course of ICP and CPP in patients developing brain death. MATERIAL AND METHODS: We analyzed retrospective data of 18 patients with ICP monitoring during the development of brain death due to primary brain lesions. ICP and CPP values were continuously measured between two clinically defined time points: 1. non-reactive and widened pupils, 2. brain death determination. We analyzed ICP and CPP at the above-mentioned end points. Additionally, we investigated maximum ICP and minimal CPP values between these time points. RESULTS: Patients developed fixed and dilated pupils with a median of 38 h before brain death determination. During brain death determination median ICP and median CPP were 103.5 and -2.5 mmHg, respectively. Maximum ICP before brain death determination was significantly higher and minimal CPP values were significantly lower compared to the time point of brain death. During the investigation period all patients experienced ICP values >95 mmHg and CPP < 10 mmHg. All but one patient had documented CPP values of ≤0 mmHg. This single patient had a minimum CPP of 8 mmHg with a maximum ICP of 145 mmHg. CONCLUSION: Cerebral perfusion pressure during brain death determination may be positive in some patients. Our results showed variable values of ICP and CPP. However, extremely elevated ICP values before or during brain death in combination with low CPP values suggest absence of cerebral perfusion. The occurrence of positive CPP values during brain death determination therefore depends on the time point at which brain death determination is performed.

Early Physiotherapy by Passive Range of Motion Does Not Affect Partial Brain Tissue Oxygenation in Neurocritical Care Patients.

Background Studies investigating multimodal cerebral monitoring including partial brain tissue oxygen monitoring (ptiO2) in neuro-intensive care patients during physiotherapy are completely lacking in the literature. Materials and Methods We performed a post hoc analysis of prospectively collected data of patients on multimodal cerebral monitoring by intracranial pressure (ICP) and cerebral perfusion pressure (CPP) measurement as well as ptiO2. Patients with severe brain diseases were treated with passive range of motion (PROM). We recorded ICP, CPP, and ptiO2 continuously every minute at baseline (15 minutes), during treatment (26 minutes), and 15 minutes after treatment with PROM. Results Overall, 25 treatment units with PROM in 10 patients with combined ICP/CPP and ptiO2 monitoring were evaluated. Median ICP, CPP, and ptiO2 at baseline were 12 ± 6.1 mm Hg, 86 ± 17.1 mm Hg, and 27 ± 14.3 mm Hg, respectively. Values for ICP, CPP, and ptiO2 did not change significantly when comparing mean values before, during, and after therapy. Conclusions Based on ptiO2 measurements, our data provide new information about the feasibility and safety of physiotherapy in patients with severe brain diseases.

[Is the time ripe for cytosorb]. / Sepsistherapie: Ist die Zeit reif für Zytokinfilter?

Hemofiltration with Cytosorb can reduce cytokines in sepsis. Since cytokines are involved in the development of vasodilatatory shock in sepsis, their reduction might improve the chance of survival in this condition. In spite of the CE-approval of Cytosorb clinical efficacy has not been proved so far. Other techniques reducing cytokines by direct or indirect manners failed to prove an influence on sepsis mortality. Moreover, the nonspecific elimination of pro- and anti-inflammatory cytokines may result in different clinical effects. Benefits and risks of nonspecific cytokine elimination may be determined by the interaction of pro- and anti-inflammatory cytokines. Therefore, the usefulness of cytokine elimination using Cytosorb cannot be estimated without clinical data. The application of cytosorb in life threatening septic shock should be accompanied by a critical discussion of the limits of these curing trials.

Does prone positioning increase intracranial pressure? A retrospective analysis of patients with acute brain injury and acute respiratory failure.

PURPOSE: The objective of our trial was to obtain more comprehensive data on the risks and benefits of kinetic therapy in intensive care patients with intracerebral pathology. METHODS: Standardized data of prone positioning in our NeuroIntensive Care Unit were collected from 2007 onward. A post hoc analysis of all available data was undertaken, with special consideration given to values of intracranial pressure (ICP), cerebral perfusion pressure (CPP) and oxygenation in correlation to prone (PP), or supine positioning (SP) of patients. Cases were considered eligible if kinetic therapy and ICP were documented. Prone positioning was performed in a 135° position for 8 h per treatment unit. RESULTS: A total of 115 patients treated with prone positioning from 2007 to 2013 were identified in our medical records. Of these, 29 patients received ICP monitoring. Overall, 119 treatment units of prone positioning with a mean duration of 2.5 days per patient were performed. The mean baseline ICP in SP was 9.5 ± 5.9 mmHg and was increased significantly during PP (p < 0.0001). There was no significant difference between CPP in SP (82 ± 14.5 mmHg) compared to PP (p > 0.05). ICP values >20 mmHg occurred more often during PP than SP (p < 0.0001) and were associated with significantly more episodes of decreased CPP <70 mmHg (p < 0.0022). The mean paO(2)/FiO(2) ratio (P/F ratio) was increased significantly in prone positioning of patients (p < 0.0001). CONCLUSIONS: The analyzed data allow a more precise understanding of changes in ICP and oxygenation during prone positioning in patients with acute brain injury and almost normal baseline ICP. Our study shows a moderate, yet significant elevation of ICP during prone positioning. However, the achieved increase of oxygenation by far exceeded the changes in ICP. It is evident that continuous monitoring of cerebral pressure is required in this patient group.

Clonidine--a potent analgesic adjuvant.

PURPOSE OF REVIEW: The alpha(2)-adrenoceptor agonist clonidine is one of the most widely investigated substances in anaesthesia and pain therapy. Recently, numerous experimental and clinical studies have allowed a better understanding of its underlying mechanisms of action and interactions with other analgesic drugs. RECENT FINDINGS: Several experimental studies have shown that clonidine may improve the analgesic effect of anti-inflammatory agents and also have significant peripheral antinociceptive effects. Volunteer and clinical studies have demonstrated analgesic effects of clonidine after systemic administration, whereas local administration of plain clonidine (e.g. intra-articular, intravenous regional) showed only limited clinical efficacy. The major clinical place of clonidine may thus be as an adjuvant to other analgesics, as shown in a number of studies in which clonidine has been investigated in combination with local anaesthetics, opioids and ketamine. An increasing number of studies have now investigated clonidine in paediatric patients and have demonstrated that the effects are generally similar to those in adults. Furthermore, it seems that in paediatric patients the side-effects of clonidine are predictable and of limited clinical importance. SUMMARY: During the past decade clonidine has been investigated as an adjuvant for general and regional anaesthesia and in the postoperative period. There is no doubt that clonidine improves analgesia after systemic, spinal or peripheral opioids, and prolongs the analgesic action of most local anaesthetics. The side-effects of usual doses of clonidine are predictable. Given the clinical experience of an increasing number of hospitals, clonidine should no longer be considered an experimental drug, but a useful addendum to the pharmacological armamentarium.