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      Cellular exposure to muscle relaxants and propofol could lead to genomic instability in vitro

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          Abstract

          Anesthesia is widely used in several medical settings and accepted as safe. However, there is some evidence that anesthetic agents can induce genomic changes leading to neural degeneration or apoptosis. Although chromosomal changes have not been observed in vivo, this is most likely due to DNA repair mechanisms, apoptosis, or cellular senescence. Potential chromosomal alterations after exposure to common anesthetic agents may be relevant in patients with genomic instability syndromes or with aggressive treatment of malignancies. In this study, the P388 murine B cells were cultured in vitro, and spectral karyotyping (SKY) was utilized to uncover genome-wide changes. Clinically relevant doses of cisatracurium and propofol increased structural and numerical chromosomal instability. These results may be relevant in patients with underlying chromosomal instability syndromes or concurrently being exposed to chemotherapeutic agents. Future studies may include utilization of stimulated peripheral blood lymphocytes to further confirm the significance of these results.

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          Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis?

          Aristomenis K. Exadaktylos, Donal J Buggy, Denis Moriarty … (2006)
          Regional anesthesia is known to prevent or attenuate the surgical stress response; therefore, inhibiting surgical stress by paravertebral anesthesia might attenuate perioperative factors that enhance tumor growth and spread. The authors hypothesized that breast cancer patients undergoing surgery with paravertebral anesthesia and analgesia combined with general anesthesia have a lower incidence of cancer recurrence or metastases than patients undergoing surgery with general anesthesia and patient-controlled morphine analgesia. In this retrospective study, the authors examined the medical records of 129 consecutive patients undergoing mastectomy and axillary clearance for breast cancer between September 2001 and December 2002. Fifty patients had surgery with paravertebral anesthesia and analgesia combined with general anesthesia, and 79 patients had general anesthesia combined with postoperative morphine analgesia. The follow-up time was 32 +/- 5 months (mean +/- SD). There were no significant differences in patients or surgical details, tumor presentation, or prognostic factors. Recurrence- and metastasis-free survival was 94% (95% confidence interval, 87-100%) and 82% (74-91%) at 24 months and 94% (87-100%) and 77% (68-87%) at 36 months in the paravertebral and general anesthesia patients, respectively (P = 0.012). This retrospective analysis suggests that paravertebral anesthesia and analgesia for breast cancer surgery reduces the risk of recurrence or metastasis during the initial years of follow-up. Prospective trials evaluating the effects of regional analgesia and morphine sparing on cancer recurrence seem warranted.
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            Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis.

            Denis Moriarty, Darren Fitzpatrick, D Buggy … (2008)
            Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia. In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia-epidural analgesia or general anesthesia-opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen. After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17-78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22-0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia. Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.
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              Propofol infusion syndrome.

              José Cardone, P Kam (2007)
              The clinical features of propofol infusion syndrome (PRIS) are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit > 10 mmol.l(-1)), rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver. There is an association between PRIS and propofol infusions at doses higher than 4 mg.kg(-1).h(-1) for greater than 48 h duration. Sixty-one patients with PRIS have been recorded in the literature, with deaths in 20 paediatric and 18 adult patients. Seven of these patients (four paediatric and three adult patients) developed PRIS during anaesthesia. It is proposed that the syndrome may be caused by either a direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. An early sign of cardiac instability associated with the syndrome is the development of right bundle branch block with convex-curved ('coved type') ST elevation in the right praecordial leads (V1 to V3) of the electrocardiogram. Predisposing factors include young age, severe critical illness of central nervous system or respiratory origin, exogenous catecholamine or glucocorticoid administration, inadequate carbohydrate intake and subclinical mitochondrial disease. Treatment options are limited. Haemodialysis or haemoperfusion with cardiorespiratory support has been the most successful treatment.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Biomed Res
                Journal ID (iso-abbrev): J Biomed Res
                Journal ID (publisher-id): JBR
                Title: Journal of Biomedical Research
                Publisher: Editorial Department of Journal of Biomedical Research
                ISSN (Print): 1674-8301
                Publication date (Print): March 2012
                Volume: 26
                Issue: 2
                Pages: 117-124
                Affiliations
                [a ]Department of Anesthesiology, Wayne State University, Detroit Medical Center, Detroit, Michigan 48201, USA;
                [b ]Laboratory of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
                [c ]Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, Maryland 20852, USA.
                Author notes
                *Corresponding author: Hong Wang, M.D., Ph.D., Professor of Anesthesiology, Wayne State/Detroit Medical Center, 3990 John R, Harper University Hospital Box 162, Detroit, Michigan 48201, USA. Tel/Fax: 1-313-745-7233/1-313-993-3889, E-mail: howang@ 123456med.wayne.edu .
                Article
                Publisher ID: jbr-26-02-117
                DOI: 10.1016/S1674-8301(12)60021-9
                PMC ID: 3597328
                PubMed ID: 23554740
                SO-VID: fdb270d0-5bd6-40ed-b8e4-34367c605adc
                Copyright © © 2012 by the Journal of Biomedical Research. All rights reserved.
                License:

                This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

                History
                Date received : 4 December 2011
                Date revision received : 5 January 2012
                Date accepted : 28 January 2012
                Categories
                Subject: Research Paper

                Keywords: spectral karyotyping (sky),genomic instability,epigenetic,p388,propofol,cisatracurium,vecuronium,pancuronium,aneuploidy
                Data availability:
                Keywords: spectral karyotyping (sky), genomic instability, epigenetic, p388, propofol, cisatracurium, vecuronium, pancuronium, aneuploidy

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