Risks and benefits of thoracic epidural anaesthesia.

Thoracic epidural anaesthesia (TEA) reduces cardiac and splanchnic sympathetic activity and thereby influences perioperative function of vital organ systems. A recent meta-analysis suggested that TEA decreased postoperative cardiac morbidity and mortality. TEA appears to ameliorate gut injury in major surgery as long as the systemic haemodynamic effects of TEA are adequately controlled. The functional benefit in fast-track and laparoscopic surgery needs to be clarified. Better pain control with TEA is established in a wide range of surgical procedures. In a setting of advanced surgical techniques, fast-track regimens and a low overall event rate, the number needed to treat to prevent one death by TEA is high. The risk of harm by TEA is even lower, and other methods used to control perioperative pain and stress response also carry specific risks. To optimize the risk-benefit balance of TEA, safe time intervals regarding the use of concomitant anticoagulants and consideration of reduced renal function impairing their elimination must be observed. Infection is a rare complication and is associated with better prognosis. Close monitoring and a predefined algorithm for the diagnosis and treatment of spinal compression or infection are crucial to ensure patient safety with TEA. The risk-benefit balance of analgesia by TEA is favourable and should foster clinical use.

[Sepsis-associated Guillain-Barré syndrome]. / Das Sepsis-assoziierte Guillain-Barré-Syndrom.

This article reports on the case of a multiple trauma patient, who was admitted to the intensive care unit with haemorrhagic shock and severe hypoxaemia. Following posttraumatic septic shock the patient developed quadriplegia 3 weeks after admittance. After having excluded any traumatic and cerebral origins, an analysis of the cerebrospinal fluid was performed and revealed a"dissociation albuminocytologique". This finding in association with limb quadriplegia led to the diagnosis of Guillain-Barré syndrome. Therapy with high-dose i.v. immunoglobulins led to a complete recovery.

Modulation of hypoxic pulmonary vasoconstriction is time and nitric oxide dependent in a peritonitis model of sepsis.

OBJECTIVE: This study assessed modulation of hypoxic pulmonary vasoconstriction (HPV) in isolated perfused rat lungs during sepsis induced by cecal ligation and perforation (CLP) at different times and its relationship to nitric oxide synthases (NOS). DESIGN AND SETTING: Prospective controlled trial in a university research laboratory. SUBJECTS: 102 male Sprague-Dawley rats. INTERVENTIONS: Groups 1-3 received sham laparotomy 6 h before lung isolation: group 1, only laparotomy; group 2, concurrently L- N6-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg); group 3, concurrently N(Omega)-nitro-L-arginine methylester (L-NAME, 5 mg/kg). Groups 4-6 received CLP 6 h before lung isolation: group 4, only CLP; group 5, concurrently L-NIL; group 6, concurrently L-NAME. The same experiments were carried out with sham and CLP treatment for 24 h (groups 7-12). Exhaled NO from rats' lungs was measured after anesthesia and tracheostomy. After the pulmonary circuit was isolated and perfused, angiotensin II (0.1 microg) was injected into the inflow tract. The lungs were ventilated with the hypoxic mixture (HPV, 3% O2) for 10 min and then again with the normoxic mixture (21% O2) for an equal period. Changes in perfusion pressure were measured. Endothelial (eNOS) and inducible NOS (iNOS) expression of the lungs was determined. MEASUREMENTS AND RESULTS: Treatment with L-NAME but not L-NIL increased HPV in sham lungs. HPV was unaltered after CLP 6 h and decreased after CLP 24 h compared to sham. In CLP animals eNOS protein expression was reduced whereas iNOS expression was increased compared to sham animals. Exhaled NO, reflecting NOS activity was twice as high in the CLP 24 h group than in the CLP 6 h group. CONCLUSIONS: In the CLP sepsis model modulation of HPV was time-dependent. In addition, vasoconstriction to hypoxic stimuli was dependent on NOS activity.

Acid dissociation and metal chelate formation equilibria of some halogenated diphenylthiocarbazones.

The acid dissociation constants (K(a)) of di-p-fluoro-, di-p-chloro-, di-p-bromo-, di-p-iodo-and di-m-trifluoromethylphenylthiocarbazones and the equilibrium formation constants (K(f(1))) of their 1:1 complexes with Co(II), Ni and Zn have been determined at 25 degrees in 50% v v aqueous dioxan at 0.10 M ionic strength. Each of the electron-withdrawing substituents gives a reduction in pK(a) roughly proportional to its Hammett sigma value, and log K(f(1)) increases linearly with pK(a).

Animal models of sepsis.

Knowledge of sepsis is growing rapidly and new pathogenetic concepts and therapeutic strategies evolve. The animal models of sepsis catalyze this development. Any model of this complex disease is inevitably a compromise between clinical realism and experimental simplification. Against the background of current pathogenetic concepts this review tries to analyze the validity and clinical relevance of each model. Endotoxemia and bacteremia represent models without an infectious focus. They reproduce many characteristics of sepsis and are highly controlled and standardized. However, they reflect a primarily systemic challenge and create neither an infectious focus nor the protracted immune reaction that characterizes sepsis. In this respect, any model with an infectious focus is decisively closer to clinical reality. In these models the peritoneal cavity is contaminated either by bacteria or inoculated feces or perforation of the bowel wall. Both the bolus injection and the implantation of carriers loaded with bacteria or feces are used. In fecal spesis and perforation models the complete spectrum of enteric pathogens is present in the septic focus and infective selection is undisturbed. Here the pathophysiologic and immunologic features of clinical sepsis are successfully reproduced. However, presumably due to inadequate control of the bacterial challenge, only poor interlaboratory standardization is possible. As to optimize models for the clinical reality the choice of an appropriate class of models is crucial. Moreover the incorporation of clinical therapy such as volume resuscitation, antibiotic therapy and surgical treatment of the septic focus is indispensable. Finally, the importance of simulation of comorbidities cannot be overemphasized.

Organ preservation with EC, HTK, and UW, solution in orthotopic rat liver transplantation. Part II. Morphological study.

The quality of organ preservation is of major importance in minimizing the incidence of primary graft nonfunction and organ rejection. For this study a new semiquantitative score was developed that grades morphologic tissue alterations in the liver according to their frequency and severity. It was applied to assess commonly used perfusion solutions for their efficacy in preventing early and late tissue damage after rat liver transplantation. For transplantation the livers were stored in Euro-Collins (EC, group I; n = 11), histidine-tryptophan-alpha-ketoglutarate (HTK, group II; n = 11), or University of Wisconsin solution (UW, group III; n = 11). Rat liver transplantation was performed with graft arterialization by the method of Engemann. Biopsies were taken for morphological examination and semiquantitative scoring during the donor operation, after 4 h of cold storage, 1 h after reperfusion, and 4 weeks postoperatively. An immunohistological bromodeoxyuridine (BrdU) assay was also performed on the day of dissection to assess the rate of hepatic proliferation. Semiquantitative morphological analysis gave widely differing results in all experimental groups after 4 h of ischemia. There was less intracellular and interstitial edema, fatty degeneration, intralobular necrosis, and hepatocellular proliferation in the HTK group than in the other groups. Neither after cold ischemia nor 1 h after reperfusion did Kupffer-cell activation occur; this is known to play a major role in the development ofischemia and reperfusion injury. Furthermore, late changes such as bile-duct proliferation and vascular and sinusoidal alterations appeared less frequently in this group. The hepato-protective powers of HTK solution might therefore be due to decreased Kupffer-cell activation.

A new clamping technique for biomechanical testing of tendons in small animals. aprobst@uni-muenster.de.

When biomechanical properties of tendons are studied, the technique of clamping the tendons in the testing machine presents a methodological challenge, especially when murine tendons are examined. These short tendons tend to rupture at the transition line to the fixation, leading to false interpretations. Therefore a new clamping technique for investigation of healthy murine Achilles tendons (n = 50) was developed, in which the intramuscular tendon fibers were fixed between two paper strips and the calcaneus was wedged into a conical slot in a wooden block and then mounted in the testing machine (n = 20). This technique was compared with the conventional clamping technique that fixes both ends of the tendon by clamps (n = 15) and an earlier described method that used glue or plastic cement for the fixation of the intramuscular tendon fibers and calcaneus in the testing machine (n = 15). When tested by the new clamping technique, 17 tendons ruptured intratendinously at a mean tensile force of 8.4 +/- 1.1 N. Three Achilles tendons (17%) tore at the site of paper fixation and had to be excluded from investigation. Data from 73% of the measurements fixed by gluing had to be excluded because slippage of the proximal tendon fibers and contamination of the tendon with glue occurred. All the conventionally clamped tendons ruptured at the site of fixation at a mean tensile force of 6.1 +/- 2.3 N (p < .05). This was 30% lower than with the new clamping technique. Thus, the newly developed clamping technique enables investigators to obtain more valid biomechanical studies of the murine Achilles tendon.

Influence of protective measures after epidural catheter disconnection on catheter lumen colonization: an in vitro study.

BACKGROUND: Epidural anaesthesia provides excellent pain therapy and reduces postoperative morbidity and mortality. Epidural haematoma and infection are catastrophic complications of this therapy. Following accidental catheter disconnection the choice is between reconnection and premature treatment termination. There is little experimental or clinical data guiding clinical decision-making after epidural catheter disconnection. AIM: Investigation of the in vitro effects of clinically applied safety measures after epidural catheter disconnection. METHODS: The proximal 20mm of epidural catheters were submerged into a suspension of 1 × 10(8)cfu Staphylococcus epidermidis. Catheters were treated by the following potentially preventive measures: (i) cutting 2 cm distal to the level of contamination, (ii) disinfection by spray-wipe, or (iii) employing ropivacaine 0.75% as flushing solution instead of normal saline. All measures were used alone, in a dual combination or all together as a triple intervention (N = 10 catheters in each group). Control catheters were not treated. After 24h of culturing, bacterial growth of the eluates was recorded. FINDINGS: All control catheters showed positive cultures. All 49 eluates of catheters that were cut as a single, dual or triple intervention remained sterile. Disinfection prevented bacterial growth in eluate of only six catheters in single or dual interventions. Ropivacaine did not prevent any bacterial growth. CONCLUSION: Only cutting of epidural catheters 20 mm distal to the level of contamination completely prevented bacterial growth. Disinfection might further reduce risk as an additive measure. This supports the clinical practice of catheter shortening and reconnection. The safe window of time and length of shortening needs to be further investigated.

Non-return valves do not prevent backflow and bacterial contamination of intravenous infusions.

Non-return valves (NRVs) are designed to avoid backflow of infusion fluid against the designated direction of flow (DDF) when more than one infusion is delivered via one venous access. We tested in vitro whether NRVs reliably prevent flow against the DDF at clinically relevant low flow rates. Since catheter-related infections caused by the infusion of contaminated fluids represent a relevant problem in patient care, we tested whether NRVs preclude bacterial contamination of infusions proximal to the NRVs and thus might play a role in preventing healthcare-associated infections. Additionally, the incidence of bacterial contamination of drips and infusion fluids in our intensive care unit (ICU) was quantified. In vitro, a low flow against the DDF of ten examples each of five different NRV models was applied and the integrity for fluid and transmigration of three different indicator micro-organisms was tested. Second, we investigated whether contamination of intravenous infusion tubing collected from patients treated on our ICU occurred. Largely independent from the model, 40% of the tested NRVs were not leak-tight for fluids when a pressure against the DDF was built up slowly. In 30%, bacteria migrated against the DDF and were detected proximal to the valve. In 6.7% of the tubing samples collected from ICU patients we detected bacterial contamination. In conclusion, contamination of drips is a relevant problem on ICU. NRVs neither reliably prevent backflow of fluids nor serve as micro-organism filters. Therefore they cannot be recommended as a way of reducing healthcare-associated infections.

Endogenous carbon monoxide production correlates weakly with severity of acute illness.

BACKGROUND AND OBJECTIVE: The enzyme haeme oxygenase-1 is highly inducible by oxidative agents. Its product carbon monoxide is thought to exert anti-inflammatory properties. We recently showed, that critically ill patients produce higher amounts of carbon monoxide compared to healthy controls. In the present study we compare endogenous carbon monoxide production with the severity of illness of intensive care unit patients. METHODS: Exhaled carbon monoxide concentration was measured in 95 mechanically ventilated, critically ill patients (mean age +/- SD, 59.5 +/- 15.7) on a carbon monoxide monitor. Measurements were taken every hour for 24 h in each patient. Data were analysed using Mann-Whitney rank sum test. Correlation analysis was performed with the Spearman's rank order correlation. RESULTS: Carbon monoxide production correlated weakly with the multiple organ dysfunction score (R = 0.27; P = 0.009). Patients suffering from cardiac disease (median 22.5, interquartile range 16.2-27.4 microL kg(-1) h(-1) vs. median 18.2, interquartile range 14.2-21.8 microL kg(-1) h(-1), P = 0.008) and critically ill patients undergoing dialysis (median 25.0, interquartile range 21.4-30.2 microL kg(-1) h(-1), vs. median 19.4, interquartile range 14.7-23.3 microL kg(-1) h(-1), P = 0.004) produced significantly higher amounts of carbon monoxide compared to critically ill controls. CONCLUSION: The findings suggest that endogenous carbon monoxide production might reflect the severity of acute organ dysfunction.