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Anaesthetic techniques for risk of malignant tumour recurrence. - The Cochrane database of systematic reviews
Surgery remains a mainstay of treatment for malignant tumours; however, surgical manipulation leads to a significant systemic release of tumour cells. Whether these cells lead to metastases is largely dependent on the balance between aggressiveness of the tumour cells and resilience of the body. Surgical stress per se, anaesthetic agents and administration of opioid analgesics perioperatively can compromise immune function and might shift the balance towards progression of minimal residual disease. Regional anaesthesia techniques provide perioperative pain relief; they therefore reduce the quantity of systemic opioids and of anaesthetic agents used. Additionally, regional anaesthesia techniques are known to prevent or attenuate the surgical stress response. In recent years, the potential benefit of regional anaesthesia techniques for tumour recurrence has received major attention and has been discussed many times in the literature. In preparing this review, we aimed to summarize the current evidence systematically and comprehensively.To establish whether anaesthetic technique (general anaesthesia versus regional anaesthesia or a combination of the two techniques) influences the long-term prognosis for individuals with malignant tumours.We searched The Cochrane Library (2013, Issue 12), PubMed (1950 to 15 December 2013), EMBASE (1974 to 15 December 2013), BIOSIS (1926 to 15 December 2013) and Web of Science (1965 to 15 December 2013). We handsearched relevant websites and conference proceedings and reference lists of cited articles. We applied no language restrictions.We included all randomized controlled trials or controlled clinical trials that investigated the effects of general versus regional anaesthesia on the risk of malignant tumour recurrence in patients undergoing resection of primary malignant tumours. Comparisons of interventions consisted of (1) general anaesthesia alone versus general anaesthesia combined with one or more regional anaesthetic techniques; (2) general anaesthesia combined with one or more regional anaesthetic techniques versus one or more regional anaesthetic techniques; and (3) general anaesthesia alone versus one or more regional anaesthetic techniques. Primary outcomes included (1) overall survival, (2) progression-free survival and (3) time to tumour progression.Two review authors independently scanned the titles and abstracts of identified reports and extracted study data.All primary outcome variables are time-to-event data. If the individual trial report provided summary statistics with odds ratios, relative risks or Kaplan-Meier curves, extracted data enabled us to calculate the hazard ratio using the hazard ratio calculating spreadsheet. To assess risk of bias, we used the standard methodological procedures expected by The Cochrane Collaboration.We included four studies with a total of 746 participants. All studies included adult patients undergoing surgery for primary tumour resection. Two studies enrolled male and female participants undergoing major abdominal surgery for cancer. One study enrolled male participants undergoing surgery for prostate cancer, and one study male participants undergoing surgery for colon cancer. Follow-up time ranged from nine to 17 years. All four studies compared general anaesthesia alone versus general anaesthesia combined with epidural anaesthesia and analgesia. All four studies are secondary data analyses of previously conducted prospective randomized controlled trials.Of the four included studies, only three contributed to the outcome of overall survival, and two each to the outcomes of progression-free survival and time to tumour progression. In our meta-analysis, we could not find an advantage for either study group for the outcomes of overall survival (hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.86 to 1.24) and progression-free survival (HR 0.88, 95% CI 0.56 to 1.38). For progression-free survival, the level of inconsistency was high. Pooled data for time to tumour progression showed a slightly favourable outcome for the control group (general anaesthesia alone) compared with the intervention group (epidural and general anaesthesia) (HR 1.50, 95% CI 1.00 to 2.25).Quality of evidence was graded low for overall survival and very low for progression-free survival and time to tumour progression. The outcome of overall survival was downgraded for serious imprecision and serious indirectness. The outcomes of progression-free survival and time to tumour progression were also downgraded for serious inconsistency and serious risk of bias, respectively.Reporting of adverse events was sparse, and data could not be analysed.Currently, evidence for the benefit of regional anaesthesia techniques on tumour recurrence is inadequate. An encouraging number of prospective randomized controlled trials are ongoing, and it is hoped that their results, when reported, will add evidence for this topic in the near future.
Anesthesia management of patients undergoing hyperthermic isolated limb perfusion with melphalan for melanoma treatment: an analysis of 17 cases. - BMC anesthesiology
Hyperthermic isolated limb perfusion (HILP) is used for patients with intractable or extensive in-transit metastatic melanoma of the limb to deliver high concentrations of cytotoxic agents to the affected limb and offers a treatment option in a disease stage with a poor prognosis when no treatment is given.In a retrospective chart review of 17 cases, we studied the anesthetic and hemodynamic changes during HILP and its management.HILP was well tolerated except in one case that is described herein. We present summary data of all cases undergoing upper and lower limb perfusion, discuss our current clinical practice of preoperative, perioperative and intraoperative patient care including the management of HILP circuit.HILP is a challenging procedure, and requires a team effort including the surgical team, anesthesia care providers, perfusionists and nurses. Intraoperatively, invasive hemodynamic and metabolic monitoring is indispensable to manage significant hemodynamic and metabolic changes due to fluid shifts and release of cytokines.
Effects of theophylline on anesthetized malignant hyperthermia-susceptible pigs. - Journal of biomedicine & biotechnology
Theophylline was shown to induce contracture development in porcine malignant hyperthermia (MH) susceptible (MHS) skeletal muscles in vitro. The purpose of the current study was to investigate the in vivo effects of theophylline in MHS and MH normal (MHN) swine.MH-trigger-free general anesthesia was performed in MHS and MHN swine. Theophylline was administered intravenously in cumulative doses up to 93.5â€‰mgÂ·kgâ»Â¹. The clinical occurrence of MH was defined by changes of central-venous pCOâ‚‚, central-venous pH, and body core temperature.Theophylline induced comparable clinical alterations in the anesthetized MHS and MHN swine, especially in regard to hemodynamic data. No pig developed hypermetabolism and/or MH according to defined criteria. All animals died with tachycardia followed by ventricular fibrillation.The cumulative theophylline doses used in this study were much higher than doses used therapeutically in humans, as demonstrated by measured blood concentrations. Theophylline is thus not a trigger of MH in genetically determined swine.
Nausea and vomiting after office-based anesthesia. - Current opinion in anaesthesiology
Safety, quality, and patient satisfaction are not only defined by the incidences of serious adverse events but also include postoperative outcomes such as postdischarge nausea and vomiting (PDNV). PDNV has a high impact on patient recovery and may influence the cost-effectiveness of office-based surgical procedures. This article reviews the incidences and risk factors for PDNV as well as medications and concepts for prophylaxis and treatment.Patients with PDNV require a longer recovery time to resume normal activities. PDNV can delay discharge from postanesthesia care units and is one of the leading causes of unexpected hospital admission after planned outpatient surgery. New data indicate that the incidence of PDNV is higher than expected and therefore we need a model that allows us to identify patients at risk for PDNV. A PDNV prediction model will help clinicians to better identify patients at risk who might benefit from long-acting antiemetics such as transdermal scopolamine, aprepitant, and/or palonosetron.PDNV is an under-recognized problem after outpatient anesthesia. Valid data for the incidence and the best treatment of PDNV after office-based anesthesia are rare. For safety, quality, and patient satisfaction, further research is needed to develop a prediction model to better identify patients at risk for PDNV in order to direct antiemetic prophylaxis for ambulatory patients undergoing office-based anesthesia.
Cumulative and bolus in vitro contracture testing with 4-chloro-3-ethylphenol in malignant hyperthermia positive and negative human skeletal muscles. - Anesthesia and analgesia
In this study we evaluated the in vitro effects of 4-chloro-3-ethylphenol (CEP) using cumulative (12.5-200 micromol/L) or bolus (75 and 100 micromol/L) administrations, on muscle specimens from malignant hyperthermia (MH) susceptible and MH nonsusceptible patients, respectively. In the cumulative CEP in vitro contracture test, contractures were significantly greater in the MH susceptible compared with the MH nonsusceptible muscles in all concentrations between 25 and 100 micromol/L. There was no overlap between the diagnostic groups at 75 micromol/L of CEP, so this test appears to be feasible for diagnosis of MH susceptibility. The two bolus tests are not diagnostically useful, as overlaps between the diagnostic groups were observed.
Ryanodine contracture threshold times for diagnosis of malignant hyperthermia susceptibility: an experimental approach from a single laboratory. - Journal of clinical anesthesia
To define threshold times for ryanodine contracture testing (RCT) using skeletal muscle specimens from malignant hyperthermia-susceptible (MHS) and control individuals.Prospective study.Malignant hyperthermia (MH) laboratory at a university hospital.8 patients with previous fulminant MH and 53 control patients undergoing in vitro contracture test (IVCT) for diagnosis of MH susceptibility.Biopsies of the quadriceps femoris muscle were performed with a 3-in-1 nerve block, with spinal anesthesia, or with trigger-free general anesthesia.Patients were classified as MHS, MH normal (MHN), or MH equivocal (MHE) by the IVCT according to the protocol of the European MH Group (EMHG). Ryanodine 1 microM was added as a bolus to the organ bath to extra vital muscle specimens. Contracture levels were defined as: 1 = start of contracture (OT; min); 2 = time (min) to reach a contracture of 2 mN, and 3 = time (min) to reach a contracture of 10 mN. The effects of ryanodine on contracture responses were measured. Ryanodine induced contractures in all specimens. MHS specimens reached all defined contracture levels significantly sooner than did the controls. Ryanodine contracture test enables a clear discrimination of MHS specimens from controls at contracture levels of OT and 2 mN, whereas at 10 mN a small overlap was observed.Using this test, which is an experimental approach from a single laboratory, an assignment to MHS or MHN is possible. To define contracture levels for RCT more precisely and to agree on commonly used thresholds, multicenter studies with larger numbers of patients are required.Copyright 2004 Elsevier Inc.
In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine. - Anesthesiology
In human skeletal muscles, the phosphodiesterase-III inhibitor enoximone induces in vitro contracture development, and it has been suggested that enoximone could trigger malignant hyperthermia (MH). In this study, the in vitro and in vivo effects of enoximone in MH-normal (MHN) and MH-susceptible (MHS) swine were investigated.Malignant hyperthermia trigger-free general anesthesia was performed in MHS and MHN swine. Skeletal muscle specimens were excised for an in vitro contracture test with 0.6 mm enoximone. Thereafter, MHS and MHN swine were exposed to cumulative administration of 0.5, 1, 2, 4, 8, 16, and 32 mg/kg enoximone intravenously. Clinical occurrence of MH was defined by a Pco(2) greater than 70 mmHg, a pH less than 7.20, and an increase in body temperature of more than 2.0 degrees C.Enoximone induced marked contractures in all MHS muscle specimens in vitro. In contrast, only small or no contracture development was observed in MHN muscle specimens, without an overlap in contractures between MHS and MHN muscles. However, in vivo, no clinical differences were found between MHS and MHN swine following cumulative enoximone doses. According to the defined criteria, none of the swine developed MH during the experiment. Furthermore, high enoximone doses induced progressive circulatory insufficiency, and after receiving 32 mg/kg enoximone, all animals died of cardiovascular failure.The cumulative enoximone doses used in this study were 30- to 50-fold higher than therapeutic doses in humans. Enoximone does not trigger MH in genetically determined swine. However, enoximone might be useful for in vitro diagnosis of MH.
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