Reinhold Függer

Endoscopic Thoracic Sympathectomy for Primary Hyperhidrosis of the Upper Limbs A Critical Analysis and Long-term Results of 480 Operations

ObjectiveThis evaluated the long-term outcome after endoscopic thoracic sympathectomy (ETS) from below D1 to D4, using a single-site access technique for primary hyperhidrosis of the upper limbs. Summary Background DataPrimary hyperhidrosis of the upper limbs is a distressing and often socially disabling condition. Endoscopic thoracic sympathectomy is considered the treatment of choice, causing minimal morbidity and high initial success rates. However, data regarding long-term results are scarce. MethodsTwo hundred seventy of 323 patients (83.7%), in whom 480 sympathectomies were performed, answered a questionnaire after a mean of 14.6 years postoperatively regarding the early postoperative result, side effects, and complications caused by the operation and long-term results with particular emphasis on patient satisfaction. ResultsThere was no postoperative mortality and no major complications requiring surgical reintervention. A majority of the patients (98.1%) were relieved, and 95.5% were satisfied initially. Permanent side effects included compensatory sweating in 67.4%, gustatory sweating in 50.7% and Homers trias in 2.5%. However, patient satisfaction declined over time, although only 1.5% recurred. This left only 66.7% satisfied, and a 26.7% partially satisfied. Compensatory and gustatory sweating were the most frequently stated reasons for dissatisfaction. Individuals operated for axillary hyperhidrosis without palmar involvement were significantly less satisfied (33.3% and 46.2%, respectively).

Surgical treatment for severe acute pancreatitis: extent and surgical control of necrosis determine outcome.

In patients operated on for severe acute pancreatitis (SAP), the factors determining outcome remain unclear. From 1986 to 1998 a total of 340 patients with a diagnosis of SAP and in need of operative treatment were admitted to the intensive care unit (ICU) of a university hospital and a secondary care hospital. The mean APACHE II score on the day of admission was 16.1 (range 8–35). All patients required operative therapy. Among the 340 patients, 270 (79.4%) had to be reoperated: 196 patients (72.6%) underwent operative revisions on demand, and 74 (27.4%) patients had preplanned reoperation. The overall mortality was 39.1% (133 patients). Septic organ failure in 126 patients (37.1%) and myocardial infarction or pulmonary embolism in 7 patients (2%) were the causes of death. The patient’s age (p <0.0002), APACHE II scores at admission (p <0.0001), presence or development of (single or multiple) organ failure (p <0.002), infection (p <0.02) and extent (p <0.04) of pancreatic necrosis, and surgical control of local necrosis (p <0.0001) significantly determined survival. SAP that requires surgical treatment is associated with high in-hospital mortality. Surgical control of local necrosis is the precondition for survival. Advanced age of the patient, high APACHE II score at admission, development of organ failure, and the extent and infection of pancreatic necrosis influence the outcome.

Relationship Between Interleukin-6 Plasma Concentration in Patients with Sepsis, Monocyte Phenotype, Monocyte Phagocytic Properties, and Cytokine Production

Monocyte phenotype, their phagocytic capacity as well as the cytokine production from 10 patients with sepsis with low interleukin-6 (IL-6) serum concentrations (<1000 pg/mL) and 8 patients with sepsis with high IL-6 (> or = 1000 pg/mL) plasma concentrations were investigated within 24 hours of fulfilling the criteria for sepsis. Monocytes from patients with high IL-6 levels had higher levels of human leukocyte antigen (HLA)-DR, HLA-ABC, CD64, and CD71, and the production of tumor necrosis factor-alpha (TNF-alpha) and IL-8, as well as the capacity of monocytes to phagocytose, was significantly elevated. Of 8 patients with high levels of plasma IL-6, 4 patients died. In contrast, all 10 patients with low plasma IL-6 concentrations survived until day 28. Patients who died had constant high IL-6 concentrations during the first 3 days, whereas IL-6 levels in patients who survived decreased by 88%. Our data indicate that IL-6 levels are a better prognostic parameter in the early phase of sepsis than the monocyte HLA-DR expression.

Attenuation of catecholamine-induced immunosuppression in whole blood from patients with sepsis.

Studies performed on healthy volunteers have revealed that catecholamines down-regulate the lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF)alpha, interleukin (IL)-6, and IL-1beta. We extended this observation and show that this effect is based on changes in the mRNA concentration of these cytokines. Catecholamines are increased in severe sepsis due to endogenous production and have to be administered exogenously when the disease has proceeded to the state of prolonged hypotension. We here investigated whether the immunomodulating effect of catecholamines could also be demonstrated in the blood of patients with prolonged severe sepsis and of those in prolonged septic shock. Blood was stimulated ex vivo with LPS in the presence and absence of epinephrine and the cytokine protein concentration was determined. In blood of healthy volunteers, epinephrine reduced the LPS-stimulated synthesis of TNFalpha by 62.5% (P< 0.0001), of IL-6 by 39% (P< 0.0001), and of IL-1beta by 40% (P= 0.015), and increased the LPS-stimulated IL-10 production by 77.8% (P < 0.0001). Correspondingly, in blood of patients with prolonged severe sepsis, TNFalpha was reduced by 67.2% (P < 0.0001) and IL-6 was reduced by 32.9% (P < 0.0001); IL-1beta and IL-10 were not modulated by catecholamines in these patients. In blood samples of patients in prolonged septic shock, epinephrine did not modulate cytokine levels of IL-6 and IL-10, and decreased TNFalpha only by 36.4% (P < 0.0001). Interestingly, epinephrine suppressed the IL-1beta production by 73% (P < 0.0001) in blood of patients in prolonged septic shock, which was twice as much as in blood samples of healthy volunteers. The altered response of septic blood to catecholamines might be due to an altered reactivity of leukocytes in the prolonged disease although an additional role of preexisting catecholamines cannot be completely excluded.

Candida infection of local necrosis in severe acute pancreatitis is associated with increased mortality.

The aim of this study was to evaluate the frequency of Candida infection of pancreatic necrosis in patients suffering from severe acute pancreatitis (SAP) and to analyze its impact on the outcome. Two-hundred and fifty consecutive patients with SAP from January 1986 to December 1998 were studied retrospectively. Their mean APACHE II score at the day of admission was in 16.1 (range 8-35). All patients were in need of operative therapy. Overall mortality was 38.8% (97 patients). One-hundred and eighty-two patients (72.8%) suffered from local infected necrosis. Among these patients, local Candida infection was observed in 31 patients, whereof 23 patients (74%) suffered from local fungal infection detected at first operation. During the course of disease, 12 patients (39%) also revealed fungemia. Local Candida infection as compared to no Candida infection was associated with an increased mortality rate (84% vs. 32%; P 0.0001). Multivariate logistic regression analysis identified APACHE II score (P < 0.0001), age of the patient (P < 0.003), extent of pancreatic necrosis (P < 0.002), and local bacterial (P < 0.04) and fungal infection (P < 0.004) as independent factors significantly contributing to mortality. SAP, requiring surgical treatment, is associated with high in-hospital mortality. Patients suffering from local Candida infection are at high risk of fatal outcome.

L-arginine deficiency after liver transplantation as an effect of arginase efflux from the graft : influence on nitric oxide metabolism

L-Arginine plays an important role in protecting animals against ammonia intoxication, enhances immune function, stimulates wound healing, and is the precursor for the endothelium-derived relaxing factor, recently recognized as nitric oxide (NO). In this study, we investigated the influence of hepatic reperfusion on amino acid metabolism after human OLT. After 10 sec of reperfusion, the arterial plasma levels of L-arginine dropped from 105 +/- 12 mumol/L to 3.8 +/- 0.6 mumol/L (P < 0.001), whereas plasma ornithine increased from 40 +/- 5.5 mumol/L to 129 +/- 15 mumol/L (P < 0.001). The reduced L-arginine levels remained subnormal for several hours after OLT. This drop in plasma L-arginine was due to an arginase release from the implanted graft. Immediately after reperfusion, the plasma concentrations of arginase increased from pretransplantation values of 18 +/- 13 IU/L to 2384 +/- 1456 IU/L (P < 0.01). Measurement of plasma nitrite (NO2-) and nitrate (NO3-), which are the stable end products of NO, revealed that NO2- decreased about 50% after reperfusion (from 1.64 +/- 0.32 mumol/L to 0.80 +/- 0.17 mumol/L; P < 0.001), whereas NO3- levels remained unchanged (76 +/- 23 mumol/L vs. 63 +/- 8 mumol/L). We conclude that hepatic reperfusion causes L-arginine deficiency by liberating high amounts of arginase from the implanted graft. This L-arginine depletion may influence the NO synthesis in patients after OLT.

Catecholamines up-regulate lipopolysaccharide-induced IL-6 production in human microvascular endothelial cells

The catecholamine‐mediated modulation of the cytokine network has primarily been demonstrated for leukocytes. Whereas catecholamines decrease the LPS‐induced production of IL‐6 by leukocytes, serum levels of IL‐6 are dramatically increased by the catecholamine epinephrine in animal endotoxemia models. We now demonstrate that epi‐nephrine as well as norepinephrine can induce IL‐6 in an endothelial cell line (HMEC‐1). Furthermore, these catecholamines could even potentiate the LPS‐induced IL‐6 protein production. The synergistic effect of cat‐echolamines and LPS could be reproduced in primary human skin microvascular endothelial cells. The cate‐cholamine‐induced IL‐6 stimulation is based on increased IL‐6 mRNA levels. RNA stability assays revealed that this regulation is not a result of enhanced RNA stability and therefore is most likely due to an increased transcription. Treatment with cycloheximide indicated that new protein synthesis is not necessary for this transcriptional up‐regulation of IL‐6 mRNA. Prein‐cubation with α and β receptor antagonists showed that the effect is mediated by β1‐ and β2‐adrenergic receptors. Thus, endothelial cells might be a possible source of increased IL‐6 production observed in situations such as stress or septic shock, in which catecholamines are elevated due to endogenous production or exogenous application.—Gornikiewicz, A., Sautner, T., Brostjan, C., Schmierer, B., Függer, R., Roth, E., Muhlbacher, F., Bergmann, M. Catecholamines up‐regu‐late lipopolysaccharide‐induced IL‐6 production in human microvascular endothelial cells. FASEB J. 14, 1093–1100 (2000)

Intraoperative estimation of endotoxin, TNFα, and IL-6 in orthotopic liver transplantation and their relation to rejection and postoperative infection

The course of endotoxemia, TNF alpha, and IL-6 during orthotopic liver transplantation was studied in 28 transplantations performed in 27 patients to evaluate their impact on early postoperative rejection and infection. The preoperative levels of endotoxin, TNF alpha, and IL-6 were not different in patients who did or did not develop postoperative rejection and/or infection within the first 10 postoperative days. At the end of surgery, TNF alpha levels increased in patients who developed rejection (median 100 pg/ml vs. 11.5 pg/ml, P = 0.004). A TNF alpha level of greater than 100 pg/ml at the end of transplantation predicted rejection in 82% of the patients. During surgery, IL-6 levels increased significantly in patients with subsequent postoperative infection, reaching significance after revascularization of the graft (median 975 pg/ml vs. 185 pg/ml, P = 0.006). An IL-6 cutoff level of 800 pg/ml predicted postoperative infection in 75% of the patients. Endotoxins were elevated intraoperatively in patients with postoperative infection, but the difference did not reach significance. There was no prognostic relevance with respect to the intraoperative values of TNF alpha and infection or IL-6 values and rejection. An intraoperative elevation of TNF alpha seems to precede early postoperative rejection, and highly increased IL-6 may be a predictor of subsequent infection in human liver transplantation.

Early effects of catecholamine therapy on mucosal integrity, intestinal blood flow, and oxygen metabolism in porcine endotoxin shock.

OBJECTIVE To determine the early effects of therapy of endotoxin (ET) shock with epinephrine, norepinephrine, or dopexamine on splanchnic circulation, oxygen metabolism, sigmoid mucosal pHi, bacterial translocation, and morphologic integrity of the ileal, colonic, and sigmoid mucosa. SUMMARY BACKGROUND DATA Conflicting concepts exist concerning the catecholamine therapy of septic shock, but little is known about the effects of catecholamine treatment on splanchnic circulation and mucosal integrity. METHODS ET shock was induced in pigs by ET infusion over 30 minutes, and animals were studied for 4 hours. All animals were resuscitated with fluid. To mimic the treatment of septic shock in humans, mean arterial pressure was maintained in two groups at >70 mm Hg with the administration of epinephrine or norepinephrine. A third group of animals received dopexamine at 7 microg/kg per minute. Systemic and splanchnic blood flow and oxygen metabolism were studied, sigmoid colon mucosal pHi was obtained tonometrically, and bacterial translocation was determined by culture of portal venous blood, mesenteric lymph nodes, liver, spleen, and lung specimens. Histologic sections of ileal, colonic, and sigmoid mucosa were morphometrically examined for therapy effects. RESULTS All investigated catecholamines increased cardiac output and systemic oxygen delivery, whereas intestinal blood flow and oxygen delivery remained unchanged. Sigmoid mucosal pHi decreased in all study animals, but the decrease was most pronounced in the epinephrine group. Pigs receiving epinephrine also showed >40% damage of the mucosa of the ileum and colon, whereas animals receiving ET alone, norepinephrine, or dopexamine showed only moderate lesions with signs of restitution. No animal showed bacterial translocation. CONCLUSIONS Systemic hemodynamics and oxygen metabolism data do not reflect intestinal perfusion. Norepinephrine or dopexamine administration in ET shock causes no additional impairment of intestinal integrity. Epinephrine therapy, in contrast, is associated with a significant reduction of mucosal pHi and considerable early mucosal damage. Its application in septic shock is hazardous.

Surgical Treatment of Severe Acute Pancreatitis: Timing of Operation is Crucial for Survival

BACKGROUND In patients operated on for severe acute pancreatitis (SAP) the impact of the timing of operation on outcome is controversial. MATERIALS AND METHODS In a retrospective analysis of a prospectively documented database, we studied 250 patients suffering from SAP, who were in need for surgical treatment during their course of disease. RESULTS From 1982 to 1998, 250 patients with the diagnosis of SAP who required operative treatment were admitted to the intensive care unit (ICU) of a university hospital. The mean APACHE II score on the day of admission was 16.1 (8-35). One hundred eighty-five patients (74%) required reoperation, of whom 111 patients (60%) underwent reoperation on demand and 74 (40%) patients a pre-planned reoperation. Overall mortality was 38.8% (97 patients). In patients who were operated during the first three weeks after onset of disease, mortality was significantly higher than in patients who were operated after three weeks (46% vs. 25%, p < 0.01). Besides patient age (p < 0.05), APACHE II score at admission (p < 0.01), multiple organ dysfunction (p < 0.01), infection of pancreatic necrosis (p < 0.05), surgical control of pancreatic necrosis (p < 0.0001), and the time of surgical intervention (p < 0.05) determined survival significantly. CONCLUSION Patients who were operated later than three weeks after onset of disease had a significantly better outcome. In patients suffering from SAP who required surgical treatment, the timing of operation is crucial for survival.