The focus of perioperative pain management should be to attempt to minimise the nociceptive input and reduce the risk of transition to central sensitisation. Gabapentinoids are being increasingly used as adjuncts for management of perioperative pain. Although gabapentinoids are classed as calcium channel blockers, their mechanisms of action are poorly understood. The analgesic effect in neuropathic pain is well evidenced but the role in postoperative pain is less certain. Medline and EMBASE database searches were conducted to identify studies relating to mechanisms of action and effects in experimental animal models of inflammatory and postoperative pain and human models of experimental pain. The effects of gabapentinoids may be attributed to depression of dorsal horn sensitivity through a multitude of mechanisms. They inhibit calcium mediated neurotransmitter release through effects on α2δ-1 subunits. They inhibit forward trafficking of α2δ-1 from the dorsal root ganglion, their recycling from endosomal compartments, thrombospondin mediated processes and stimulate glutamate uptake by excitatory amino acid transporters. Mechanisms not directly related to neurotransmitter release at dorsal horn include inhibition of descending serotonergic facilitation, stimulation of descending inhibition, anti-inflammatory actions, and influence on the affective component of pain. Gabapentinoids are effective analgesics in most animal models of inflammation and postoperative pain but effects in human models are variable.
The gabapentinoids are often recommended as first-line treatments for the management of neuropathic pain. The differing pharmacodynamic and pharmacokinetic profiles can have implications for clinical practice. This article has summarised these key differences. In addition to their use in managing neuropathic pain, gabapentinoids are increasingly being used for off-label conditions despite the lack of evidence. Prescription rates for off-label conditions have overtaken that for on-label use. Similarly, the use of gabapentinoids in the perioperative period is now embedded in clinical practice despite conflicting evidence. This article summarises the risks associated with this increasing use. There is increasing evidence of the potential to cause harm in vulnerable populations such as the elderly and increasing prevalence of abuse. The risk of respiratory depression in combination with opioids is of particular concern in the context of the current opioid crisis. This article describes the practical considerations involved that might help guide appropriate prescribing practices.
† The authors systematically reviewed the prediction of mortality risk after oesophagectomy for cancer. † They found generally unsatisfactory performance in commonly used models, and recommend further work in developing and validating new prediction models via large data sets. Summary. Predicting risk of perioperative mortality after oesophagectomy for cancer may assist patients to make treatment choices and allow balanced comparison of providers. The aim of this systematic review of multivariate prediction models is to report their performance in new patients, and compare study methods against current recommendations. We used PRISMA guidelines and searched Medline, Embase, and standard texts from 1990 to 2012. Inclusion criteria were English language articles reporting development and validation of prediction models of perioperative mortality after open oesophagectomy. Two reviewers screened articles and extracted data for methods, results, and potential biases. We identified 11 development, 10 external validation, and two clinical impact studies. Overestimation of predicted mortality was common (5-200% error), discrimination was poor to moderate (area under receiver operator curves ranged from 0.58 to 0.78), and reporting of potential bias was poor. There were potentially important case mix differences between modelling and validation samples, and sample sizes were considerably smaller than is currently recommended. Steyerberg and colleagues' model used the most 'transportable' predictors and was validated in the largest sample. Most models have not been adequately validated and reported performance has been unsatisfactory. There is a need to clarify definition, effect size, and selection of currently available candidate predictors for inclusion in prediction models, and to identify new ones strongly associated with outcome. Adoption of prediction models into practice requires further development and validation in well-designed large sample prospective studies.
Despite the high colonization rate of the temporary extension wire, there were no surgical site infections. We conclude that provided appropriate strategies for the management of surgical site infections are implemented, the 2-stage cut-down procedure is a safe approach that is not associated with a higher incidence of infection.
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