Levobupivacaine plasma concentrations following major liver resection.

PURPOSE: Levobupivacaine is metabolized hepatically. Whether postoperative epidural analgesia with levobupivacaine can lead to critical accumulation in patients undergoing major hepatic resection is unknown. Therefore, levobupivacaine concentrations were prospectively monitored in patients undergoing major liver resection and compared to patients undergoing rectal resection, who served as controls. Furthermore, we correlated levobupivacaine plasma concentrations with established liver function tests. METHODS: We analyzed plasma concentrations of levobupivacaine in 20 patients each scheduled for major liver or anterior rectal resection. All patients received general and epidural anesthesia (10 ml levobupivacaine 0.5% followed by 10 ml levobupivacaine 0.375% every 90 min) and postoperative continuous epidural analgesia (levobupivacaine 0.2%). Intraoperatively, and for 3 days postoperatively, levobupivacaine plasma concentrations were measured and correlated with bilirubin, fibrinogen, indocyanine green (ICG) clearance, and cholinesterase activity. Data (mean ± SD) were analyzed by two-way analysis of variance (ANOVA) with post hoc analysis or regression analysis (P < 0.05). RESULTS: Intraoperatively and postoperatively, patients undergoing liver resection revealed significantly higher levobupivacaine concentrations (P= 0.0013 and P = 0.0016, respectively). Furthermore, significant differences were found for bilirubin (P = 0.0002), fibrinogen (P = 0.0002), and ICG (P < 0.0001). Highest levobupivacaine concentration correlated significantly with lowest ICG (P = 0.0004; R = 0.69), highest bilirubin (P = 0.0267; R = 0.49), lowest fibrinogen concentration (R = 0.32), but not with cholinesterase activity (R = 0.02). CONCLUSION: Patients undergoing liver resection revealed significantly higher levobupivacaine concentrations compared to patients undergoing anterior rectal resection. However, although intraoperative levobupivacaine concentrations remained below 2.0 µg/ml, postoperative concentrations accumulated to a concentration above this threshold. This risk of levobupivacaine accumulation in patients with compromised liver function correlated best with ICG clearance.

Retroperitoneoscopic adrenalectomy in Conn's syndrome caused by adrenal adenomas or nodular hyperplasia.

BACKGROUND: In patients with primary hyperaldosteronism, solitary adrenal adenomas are an indication for surgical intervention. In contrast, adrenal hyperplasia is almost exclusively treated by drugs. PATIENTS AND METHODS: In a prospective clinical study 183 patients (81 men, 102 women; age 49.6+/-12.8 years) with Conn's syndrome were operated on using the posterior retroperitoneoscopic approach. Tumor size ranged from 0.2 to 5.0 cm (mean 1.5+/-0.8 cm). Final histology described a solitary adenoma in 127 patients and adrenal hyperplasia in 56 patients. Partial adrenalectomies were performed in 47 operations. RESULTS: The perioperative complication rate was 4%, mortality zero. In none of the cases was conversion to open surgery necessary. The mean operating time was 58+/-32 minutes (range 20-230 minutes) and was associated with sex (p<0.001) but not with the extent of resection (partial vs. total, p=0.51) or with tumor size (1.5 cm; p=0.43) or tumor site (p=0.77). Median blood loss was 15 ml. Median duration of postoperative hospitalization was 4 days. After a mean follow-up of nearly 5 years, 96% of patients are normokalemic, 30% of patients are cured (normotensive without medication), and 87% showed an improvement of hypertension (normotensive without or with reduced medication). Cure of hypertension depended on the patient's age (p<0.001) and sex (p<0.001), duration of hypertension (p<0.05), and histomorphology (p<0.001). Improvement of hypertension was not associated with any of these factors. CONCLUSIONS: Retroperitoneoscopic removal of adrenal glands in patients with Conn's syndrome is a safe, rapidly performed surgical procedure and can thus be considered as first choice option for treatment of both solitary adrenal adenomas and hyperplasia presenting with a clinically predominating nodule.

Posterior retroperitoneoscopic adrenalectomy--results of 560 procedures in 520 patients.

BACKGROUND: The posterior retroperitoneoscopic adrenalectomy is less popular than the laparoscopic transabdominal method. Due to the direct approach to the adrenal glands, however, the posterior retroperitoneal access is easy to use and may offer advantages not available with other endoscopic procedures for adrenalectomy. METHODS: Between July 1994 and March 2006, we performed 560 adrenalectomies (right side: n = 258; left side: n = 302) by the posterior retroperitoneoscopic approach in 520 patients (200 male, 320 female; age, 10 to 83 years). Of the 520 patients, 21 suffered from Cushing's disease, 499 patients had adrenal tumors (157 Conn's adenomas, 120 pheochromocytomas [13 bilateral], 110 Cushing's adenomas [6 bilateral], and 112 other tumors). Tumor size ranged from 0.5 to 10 cm (mean, 2.9 +/- 1.7 cm). The procedures were performed with the patients in the prone position usually with 3 trocars. RESULTS: Mortality was zero. Conversions to open or laparoscopic lateral surgery were necessary in 9 patients (1.7%). Major complications occurred in 1.3% of patients, minor complications in 14.4%. Mean operating time was 67 +/- 40 min and declined significantly (P < .001) from the early procedures (106 +/- 46 min) to the later operations (40 +/- 15 min). CONCLUSIONS: The posterior retroperitoneoscopic adrenalectomy is a safe and fast procedure. In experienced hands, this method represents the ideal approach in adrenal surgery.

Laparoscopic and retroperitoneoscopic treatment of pheochromocytomas and retroperitoneal paragangliomas: results of 161 tumors in 126 patients.

BACKGROUND: Laparoscopic and retroperitoneoscopic excisions of pheochromocytomas and retroperitoneal paragangliomas are challenging surgical procedures because of extensive intraoperative catecholamine release, extreme vascularization, and demanding localization. MATERIALS: In a prospective clinical study 161 chromaffine neoplasias (134 pheochromocytomas, 27 paragangliomas) were removed endoscopically in 126 patients (67 males, 59 females, age 41.7 +/- 16.4 years; 130 operations). Six patients showed multiple (2-5) tumors. Tumor size ranged from 0.5 to 12 cm (mean 3.5 +/- 1.9 cm). Forty-two patients suffered from hereditary diseases. Twenty-four patients had bilateral adrenal diseases; in 14 patients pheochromocytomas were removed on both sides synchroneously. Ten neoplasias were local or loco-regional recurrences (7 pheochromocytomas, 3 paragangliomas). The laparoscopic route was chosen in 16 operations; the retroperitoneoscopic technique was performed in 128 others. Partial adrenalectomies were performed in 57 operations (in all but one of the patients with bilateral disease). High-dosage alpha-blockade with phenoxybenzamine was routinely used. RESULTS AND DISCUSSION: Conversion to open surgery occurred once. Perioperative complications were minor (17%); mortality was zero. Operating time for unilateral retroperitoneoscopically removed primary pheochromocytomas (n = 113) was 82 +/- 49 minutes (range: 20-300 minutes) and depended on tumor size (< 3 cm vs. > or = 3 cm; P < 0.05) and gender (P < 0.001), but not on extent of resection (partial vs. total, P = 0.266). Operating time for paragangliomas ranged from 55 to 600 minutes. Median blood loss was 20 ml. Median duration of postoperative hospitalization was 4 days. In 22 of 24 patients with bilateral disease, complete preservation of cortical function was achieved. Locoregional and/or distant metastatic recurrence were found in 5 patients. CONCLUSIONS: Endoscopic removal of solitary, bilateral, multiple, and recurrent pheochromocytomas and retroperitoneal paragangliomas is feasible and safe, but surgeons need extensive experience in minimally invasive techniques, as well as in endocrine surgery.

Local and systemic chemotherapy with taurolidine and taurolidine/heparin in colon cancer-bearing rats undergoing laparotomy.

Experimental studies in the therapy of malignant abdominal tumors have shown that different cytotoxic agents suppress the intraperitoneal tumor growth. Nevertheless, a general accepted approach to prevent tumor recurrences does not exist. Following subcutaneous and intraperitoneal injection of 10(4) colon adenocarcinoma cells (DHD/K12/TRb), the influences of both taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumor growth was investigated in 105 rats undergoing midline laparotomy. The animals were randomized into 7 groups and operated on during 30 min. To investigate the intraperitoneal (local) influence of either taurolidine or heparin on tumor growth, the substances were applied intraperitoneally. Systemic and intraperitoneal effects were evaluated after intravenous injection of the substances. Both application forms were also combined to analyze synergistic effects. Tumor weights, as well as the incidence of abdominal wound metastases, were determined four weeks after the intervention. In order to evaluate the effects of the agents, blood was taken to determine the peripheral leukocytes counts. Intraperitoneal tumor growth in rats receiving intraperitoneal application of taurolidine (median 7.0 mg, P = 0.05) and of taurolidine/heparin (median 0 mg, P = 0.02) was significantly reduced when compared to the control group (median 185 mg). The simultaneous instillation of both agents also reduced the intraperitoneal tumor growth (median 4 mg, P = 0.04), while the intravenous injection of the substances caused no local effect. In contrast, the subcutaneous tumor growth did not differ among all groups. In all groups, abdominal wound recurrences were rare and did not differ. Independent of the agents and the application form, the operation itself caused a slight leukopenia shortly after the operation and a leukocytosis in the following course. Intraperitoneal therapy of either taurolidine or in combination with heparin inhibits local tumor growth and abdominal wound recurrences in rats undergoing midline laparotomy. Neither the intraperitoneal nor the intravenous application or the combination of the two agents influenced the subcutaneous tumor growth. The substances did not alter the changes of peripheral leukocytes.

Omega-3 fatty acid supplementation increases anti-inflammatory cytokines and attenuates systemic disease sequelae in experimental pancreatitis.

BACKGROUND: The cytokines involved in the systemic inflammatory response in acute pancreatitis (AP) comprise lipid mediators (eg, prostanoids, thromboxanes, leukotrienes) generated from arachidonic acid (AA) and eicosapentaenoic acid (EPA). The AA-derived mediators are generated from omega-6-fatty acid (FA) and have strong proinflammatory effects and the EPA-derived mediators generated from omega-3-fatty acid are less active or even exhibit anti-inflammatory effects. Basic parenteral nutrition delivers omega-6-FA and omega-3-FA at a ratio of approximately 7:1. AIM: To investigate whether altering the FA composition by fish oil supplementation (omega-3-FA) affects cytokine production and the parameters reflecting systemic disease severity in experimental AP. METHODS: Severe AP was induced in 30 rats by standardized intraductal infusion of bile salt and IV cerulein. Six hours after AP induction, rats were randomized to TPN using commercial solutions with identical amounts of glucose, amino acids, and fat but different FA compositions: group 1 received a soybean-based fat solution without additional fish oil and group 2 was supplemented with 0.2 g/kg per day fish oil. TPN was continued for 2 days. Serum concentrations of IL-6 and IL-10 were measured before and after AP induction and at 24 and 48 hours after starting TPN. Routine cardiorespiratory and renal parameters were monitored to assess the systemic response at the organ level. RESULTS: Animals treated with fish oil had significantly higher IL-10 values (at 24 hours, 63 +/- 7 versus 46 +/- 3 pg/mL), produced more urine (28 +/- 0.9 versus 21 +/- 1.6 mL), and had significantly fewer episodes of respiratory dysfunction (defined as a pO2 < 80 mm Hg or pCO2 > 50 mm Hg for >15 minutes; 29% versus 67%) during the observation period. CONCLUSIONS: Altering eicosanoid mediator precursor availability by infusion of (omega-3 fatty acid increases anti-inflammatory cytokines in this model of AP. This together with improved renal and respiratory function suggests that the systemic response to pancreatic injury is attenuated.