Systemic lidocaine shortens length of hospital stay after colorectal surgery: a double-blinded, randomized, placebo-controlled trial.

OBJECTIVE: To characterize the beneficial effects of perioperative systemic lidocaine on length of hospital stay, gastrointestinal motility, and the inflammatory response after colorectal surgery. SUMMARY BACKGROUND DATA: Surgery-induced stimulation of the inflammatory response plays a major role in the development of several postoperative disorders. Local anesthetics possess anti-inflammatory activity and are thought to positively affect patients' outcome after surgery. This double-blinded, randomized, and placebo-controlled trial aimed to evaluate beneficial effects of systemic lidocaine and to provide insights into underlying mechanisms. METHODS: Sixty patients undergoing colorectal surgery, not willing or unable to receive an epidural catheter, were randomly assigned to lidocaine or placebo treatment. Before induction of general anesthesia, an intravenous lidocaine bolus (1.5 mg/kg) was administered followed by a continuous lidocaine infusion (2 mg/min) until 4 hours postoperatively. Length of hospital stay, gastrointestinal motility, and pain scores were recorded and plasma levels or expression of pro- and anti-inflammatory mediators determined. RESULTS: Lidocaine significantly accelerated return of bowel function and shortened length of hospital stay by one day. No difference could be observed in daily pain ratings. Elevated plasma levels of IL-6, IL-8, complement C3a, and IL-1ra as well as expression of CD11b, L- and P-selectin, and platelet-leukocyte aggregates were significantly attenuated by systemic lidocaine. CONCLUSIONS: Perioperative intravenous lidocaine not only improved gastrointestinal motility but also shortened length of hospital stay significantly. Anti-inflammatory activity modulating the surgery-induced stress response may be one potential mechanism. Systemic lidocaine may thus provide a convenient and inexpensive approach to improve outcome for patients not suitable for epidural anesthesia.

Different angiogenic phenotypes in primary and secondary glioblastomas.

Primary and secondary glioblastomas (pGBM, sGBM) are supposed to evolve through different genetic pathways, including EGF receptor and PDGF and its receptor and thus genes that are involved in tumor-induced angiogenesis. However, whether other angiogenic cytokines are also differentially expressed in these glioblastoma subtypes is not known so far, but this knowledge might be important to optimize an antiangiogenic therapy. Therefore, we studied the expression of several angiogenic cytokines, including VEGF-A, HGF, bFGF, PDGF-AB, PDGF-BB, G-CSF and GM-CSF in pGBMs and sGBMs as well as in gliomas WHO III, the precursor lesions of sGBMs. In tumor tissues, expression of all cytokines was observed albeit with marked differences concerning intensity and distribution pattern. Quantification of the cytokines in the supernatant of 30 tissue-corresponding glioma cultures revealed a predominant expression of VEGF-A in pGBMs and significantly higher expression levels of PDGF-AB in sGBMs. HGF and bFGF were determined in nearly all tumor cultures but with no GBM subtype or malignancy-related differences. Interestingly, GM-CSF and especially G-CSF were produced less frequently by tumor cells. However, GM-CSF secretion occurred together with an increased number of simultaneously secreted cytokines and correlated with a worse patient prognosis and may thus represent a more aggressive angiogenic phenotype. Finally, we confirmed an independent contribution of each tumor-derived cytokine analyzed to tumor-induced vascularization. Our data indicate that an optimal antiangiogenic therapy may require targeting of multiple angiogenic pathways that seem to differ markedly in pGBMs and sGBMs.