BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013.
OBJECTIVES: To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS.
METHODS: We identified Cochrane reviews and non-Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022, with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria. Two overview authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well-being, and participants' ratings of satisfaction or improvement with treatment. MAIN RESULTS: We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non-Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high-certainty evidence for any comparison. There was low-certainty evidence that bisphosphonates may reduce pain intensity post-intervention (standardised mean difference (SMD) -2.6, 95% confidence interval (CI) -1.8 to -3.4, P = 0.001; I2 = 81%; 4 trials, n = 181) and moderate-certainty evidence that they are probably associated with increased adverse events of any nature (risk ratio (RR) 2.10, 95% CI 1.27 to 3.47; number needed to treat for an additional harmful outcome (NNTH) 4.6, 95% CI 2.4 to 168.0; 4 trials, n = 181). There was moderate-certainty evidence that lidocaine local anaesthetic sympathetic blockade probably does not reduce pain intensity compared with placebo, and low-certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. No effect size was reported for either comparison. There was low-certainty evidence that topical dimethyl sulfoxide may not reduce pain intensity compared with oral N-acetylcysteine, but no effect size was reported. There was low-certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine stellate ganglion block, but no effect size was reported. For a wide range of other commonly used interventions, the certainty in the evidence was very low and provides insufficient evidence to either support or refute their use. Comparisons with low- and very low-certainty evidence should be treated with substantial caution. We did not identify any RCT evidence for routinely used pharmacological interventions for CRPS such as tricyclic antidepressants or opioids.
AUTHORS' CONCLUSIONS: Despite a considerable increase in included evidence compared with the previous version of this overview, we identified no high-certainty evidence for the effectiveness of any therapy for CRPS. Until larger, high-quality trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult. Current non-Cochrane systematic reviews of interventions for CRPS are of low methodological quality and should not be relied upon to provide an accurate and comprehensive summary of the evidence.
Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.
HINTERGRUND: Die antiepileptische Medikamente für die Behandlung von verschiedenen Arten von neuropathischem Schmerz verwendet worden, und manchmal Fibromyalgie. Unser Verständnis von Qualitätsstandards in der chronischen Schmerz Studien hat sich verbessert, neue Quellen der möglichen Befangenheit enthalten. Individuelle Cochrane-Reviews mit diesen neuen Standards einzelnen Antiepileptika geprüft. Eine frühe Kritik aus dieser Gruppe, die ursprünglich im Jahr 1998 veröffentlicht wurde, war 'Antikonvulsiva bei akuten und chronischen Schmerzen "betitelt. Diese Übersicht umfasst nun die neuropathischen Schmerzen Aspekt dieser ursprünglichen Kritik, die 2009 zurückgezogen wurde.
ZIELE: Um einen Überblick über die relative analgetische Wirksamkeit von Antiepileptika, die mit Placebo bei neuropathischen Schmerzen und Fibromyalgie verglichen wurden, bereitzustellen und zu unerwünschten Ereignissen bei ihrer Verwendung zu melden.
Methoden: Wir enthalten Bewertungen theCochrane Database of Systematic Reviews veröffentlicht bis August 2013 (Heft 7). Wir extrahierten Informationen von jeder Kritik an Maßnahmen der Wirksamkeit und der Schaden, und methodischen Details über die Anzahl der Teilnehmer, die Studiendauer und die Anrechnungsmethoden, um mögliche Verzerrungen in verfügbaren Daten zu beurteilen.
Wir analysierten Wirksamkeitsdaten für jede schmerzhafte Zustand in drei Stufen, je nach Ergebnis und die Freiheit von bekannten Quellen von Bias. Die erste Stufe erfüllt derzeit besten Standards - mindestens 50% Reduktion der Schmerzintensität über der Basislinie (oder dessen Äquivalent), ohne den Einsatz von letzten vorwärts (LOCF) für Aussteiger, einer Intention-to-treat (ITT)-Analyse, parallel durchgeführt Beobachtung Gruppe untersucht mit mindestens 200 Teilnehmern nachhaltig 8 Wochen oder mehr. Die zweite Stufe verwendet die Daten von mindestens 200 Teilnehmer in denen eine oder mehrere der oben genannten Bedingungen nicht erfüllt wurden. Die dritte Stufe des Beweises, um Daten von weniger als 200 Teilnehmern oder mit einigen wichtigen methodischen Probleme, die Auslegung begrenzt zusammen.
HAUPTERGEBNISSE: Es wurden keine Studien berichtet erstklassige Ergebnisse.
Nur für Gabapentin und Pregabalin fanden wir recht gute zweite Ebene Belege für die Wirksamkeit bei der schmerzhaften diabetischen Neuropathie und Postzosterschmerz. Darüber hinaus ist für Pregabalin, fanden wir Hinweise auf Wirksamkeit bei zentralen neuropathischen Schmerzen und Fibromyalgie. Punktschätzungen von Zahlen benötigt, um für einen zusätzlichen positiven Effekt (NNT) zu behandeln waren im Bereich von 4 bis 10 für das wichtigste Ergebnis der Schmerzintensität Reduktion gegenüber dem Ausgangs von 50% oder mehr.
Für andere Antiepileptika es keine Beweise (Clonazepam, Phenytoin), so wenig dafür, dass keine vernünftige Urteil könnte über die Wirksamkeit (Valproinsäure), niedrige Qualität Beweise wahrscheinlich mit einer Reihe von Vorurteilen zu überschätzen Wirksamkeit (Carbamazepin) zu sein, gemacht werden, oder vernünftige Qualität Beweise, die wenig oder keine Wirkung (Lamotrigin, Oxcarbazepin, Topiramat). Lacosamid aufgezeichnet, eine triviale statistische Überlegenheit gegenüber Placebo, es sei unzuverlässig zu dem Schluss, dass es keine Wirkung, wo es möglich war, hatte erhebliche Voreingenommenheit.
Alle Vorteile der Behandlung kam mit einem hohen Risiko von Nebenwirkungen und Entzugs aufgrund von Nebenwirkungen, aber schwerwiegende unerwünschte Ereignisse wurden nicht signifikant erhöht, jedoch mit Oxcarbazepin.
Schlussfolgerungen der Autoren: Klinische Studie Beweise unterstützt nur die Verwendung von Gabapentin und Pregabalin in einigen neuropathischen Schmerzen Bedingungen (schmerzhafter diabetischer Neuropathie, Postzosterschmerz und zentralen neuropathischen Schmerzen) und Fibromyalgie. Nur eine Minderheit der Menschen erreicht annehmbar gute Schmerzlinderung mit jeder Droge, aber es ist bekannt, dass die Lebensqualität und Funktion deutlich verbessert mit dem Ergebnis von mindestens 50% Reduktion der Schmerzintensität. Für andere Antiepileptika es keine Beweise, keine ausreichenden Beweise oder Hinweise auf einen Mangel an Wirkung, diese enthalten Carbamazepin. Erkenntnisse aus der klinischen Praxis und Erfahrung ist, dass einige Patienten können gute Ergebnisse mit anderen als Gabapentin oder Pregabalin Antiepileptika zu erreichen.
Es gibt keine festen Beweise, um die wichtigen Fragen rund um die pragmatischen Patienten sollte die Droge, und in welcher Reihenfolge die Drogen verwendet werden soll beantworten. Es ist eine klinische Wirksamkeit Forschungsagenda, Beweise über Strategien eher als Interventionen, die insgesamt besten Ergebnisse in einer Bevölkerung zu produzieren, in kürzester Zeit und zu den geringsten Kosten für Gesundheitsdienstleister.
Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013.
OBJECTIVES:
To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS.
METHODS:
We identified Cochrane reviews and non-Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022, with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria. Two overview authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well-being, and participants' ratings of satisfaction or improvement with treatment.
MAIN RESULTS:
We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non-Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high-certainty evidence for any comparison. There was low-certainty evidence that bisphosphonates may reduce pain intensity post-intervention (standardised mean difference (SMD) -2.6, 95% confidence interval (CI) -1.8 to -3.4, P = 0.001; I2 = 81%; 4 trials, n = 181) and moderate-certainty evidence that they are probably associated with increased adverse events of any nature (risk ratio (RR) 2.10, 95% CI 1.27 to 3.47; number needed to treat for an additional harmful outcome (NNTH) 4.6, 95% CI 2.4 to 168.0; 4 trials, n = 181). There was moderate-certainty evidence that lidocaine local anaesthetic sympathetic blockade probably does not reduce pain intensity compared with placebo, and low-certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. No effect size was reported for either comparison. There was low-certainty evidence that topical dimethyl sulfoxide may not reduce pain intensity compared with oral N-acetylcysteine, but no effect size was reported. There was low-certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine stellate ganglion block, but no effect size was reported. For a wide range of other commonly used interventions, the certainty in the evidence was very low and provides insufficient evidence to either support or refute their use. Comparisons with low- and very low-certainty evidence should be treated with substantial caution. We did not identify any RCT evidence for routinely used pharmacological interventions for CRPS such as tricyclic antidepressants or opioids.
AUTHORS' CONCLUSIONS:
Despite a considerable increase in included evidence compared with the previous version of this overview, we identified no high-certainty evidence for the effectiveness of any therapy for CRPS. Until larger, high-quality trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult. Current non-Cochrane systematic reviews of interventions for CRPS are of low methodological quality and should not be relied upon to provide an accurate and comprehensive summary of the evidence.
