Epidural analgesia? A prospective analysis of perioperative coagulation in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is beneficial in peritoneal carcinomatosis. Epidurals provide excellent pain relief for laparotomies. Coagulopathy (platelet count <100 × 109/L, INR>1.5 or PTT >45) occurs with CRS and HIPEC, increasing risk for bleeding complications with epidurals. This prospective study characterizes clot kinetics with thromboelastography (TEG) to determine suitability for epidural analgesia. METHODS: After Research Ethics approval, thirty consented patients had blood collected. Primary data collected included TEG and conventional coagulation measures (platelets, PTT and INR). Secondary data collected included demographics, disease, surgical, intraoperative factors and complications from epidural placement. RESULTS: Of 30 patients analyzed, two had incomplete data. Four developed abnormal coagulation between the second and fifth post-operative day. For all patients, TEG values remained normal. Postoperative INR was elevated until day 3 (all INR < 1.5). 17 patients received epidural analgesia, 3 demonstrated abnormal conventional coagulopathic criteria despite normal TEG. CONCLUSIONS: In this study CRS and HIPEC do not contribute to the conventional definition of clinical coagulopathy. Clot kinetics indicate that epidural catheters may be recommended for post-operative analgesia.

Surface anatomy as a guide to vertebral level for thoracic epidural placement.

BACKGROUND: Precise placement of thoracic epidural catheters is required to optimize postoperative analgesia and minimize adverse effects. Previous research demonstrated that anesthesiologists are inaccurate when using surface anatomy to locate vertebral levels. In this study, we compared the accuracy of two different landmarks to identify the seventh thoracic (T7) spinous process. METHODS: Two-hundred-ten patients referred for chest radiography were randomized to two groups. With patients in the anatomic (upright) position, one investigator identified and placed a radioopaque marker over the presumed T7 spinous process using either the vertebra prominens (C7) or the inferior scapular tip as a surface landmark. A radiologist, blinded to the identification technique, reported the spinous process corresponding to the radioopaque label. Marker positions were then compared using the Fisher's exact test. The influence of patient characteristics (age, gender, Body Mass Index [BMI], and height and weight) on accuracy was also examined. RESULTS: Patient characteristics were similar between groups. The T7 spinous process was identified correctly 29% of the time with the C7 landmark and 10% of the time with the scapular landmark (P < 0.001). Accuracy improved for T7 +/- 1 level to 78% and 42%, respectively (P = 5.84 x 10(-8)). Errors were more common in the caudal direction (i.e., T8 or T9 identified). The C7 landmark was more accurate among those with a BMI <25 (P = 6.51 x 10(-5)). In those with a BMI >or=25, both landmarking methods were frequently inaccurate (P = 0.312). CONCLUSIONS: For patients with a BMI <25, the T7 spinous process can be reliably identified to within one interspace in 78% of patients using the C7 (vertebra prominens) surface landmark. Neither the vertebra prominens nor the tip of scapula is a reliable landmark to identify T7 in patients with a BMI >or=25.

Strain-dependent induction of enterocyte apoptosis by Giardia lamblia disrupts epithelial barrier function in a caspase-3-dependent manner.

We recently demonstrated that Giardia lamblia rearranges cytoskeletal proteins and reduces transepithelial electrical resistance. The effect of G. lamblia on enterocyte apoptosis is unknown, and a possible link between microbially induced enterocyte apoptosis and altered epithelial permeability has yet to be established. The aim of this study was to assess whether G. lamblia induces enterocyte apoptosis in duodenal epithelial monolayers and whether this effect increases epithelial permeability. Monolayers of nontransformed human duodenal epithelial cells were incubated with sonicated or live G. lamblia trophozoites (NF, S2, WB, or PB strains) for 8, 24, and 48 h. Cell cultures were assessed for apoptosis by Hoechst fluorescence staining, enzyme-linked immunosorbent assay for apoptotic nucleosomes, and electron microscopy. In separate experiments, monolayers were pretreated with or without 120 microM caspase-3 inhibitor (Z-DEVD-FMK) for 1 h and were assessed for production of apoptotic nucleosomes, tight junctional integrity (with fluorescent ZO-1 staining followed by confocal laser microscopy), and transepithelial permeability for fluorescein isothiocyanate-dextran. G. lamblia strains NF and S2, but not strains WB or PB, induced enterocyte apoptosis within the monolayers, and this effect was inhibited by Z-DEVD-FMK pretreatment. Using the G. lamblia NF isolate, additional experiments investigated the possible link between enterocyte apoptosis and altered epithelial permeability. G. lamblia NF disrupted tight junctional ZO-1 and increased epithelial permeability, but these effects were also prevented by pretreatment with the caspase-3 inhibitor. These findings indicate that strain-dependent induction of enterocyte apoptosis may contribute to the pathogenesis of giardiasis. This effect is responsible for a loss of epithelial barrier function by disrupting tight junctional ZO-1 and increasing permeability in a caspase-3-dependent manner.