[Interdisciplinary position paper "Perioperative pain management"]. / Interdisziplinäres Positionspapier "Perioperatives Schmerzmanagement".

Despite many positive developments, postoperative pain and its treatment is still not always given the necessary attention. Severe pain after surgical procedures affects a significant proportion of patients. This very fact is not only detrimental to the immediate recovery process, but can also form the basis for the development of chronic pain conditions.An adequate and effective management of perioperative pain requires appropriate organizational structures. This multidisciplinary paper which was initiated by the Austrian Society for Anaesthesiology and Intensive Care and the Austrian Pain Society and developed together with numerous specialist and professional societies dealing with the subject aims at supporting the organization of perioperative pain management structures and to make best use of proven concepts. Additional recommendations describe specific interventions for selected types of intervention.

Diameter-related variations of geometrical, mechanical, and mass fraction data in the anterior portion of abdominal aortic aneurysms.

OBJECTIVE: Maximum aortic diameter is an important measure in rupture prediction of abdominal aortic aneurysms (AAAs). Analyzing the variations of geometrical, material, and biochemical properties with increased AAA diameters advances understanding of the effect of lesion enlargement on patient specific vascular properties. METHODS: 96 AAA samples were harvested during open surgical aneurysm repair. Geometrical factors such as the maximum intraluminal thrombus (ILT) thickness, wall thickness, and AAA expansion rate were measured. Biaxial extension and peeling tests were performed to characterize the biaxial mechanical responses and to quantify the dissection properties of aneurysmal tissue. Mass fraction analysis quantified the dry weight percentages of elastin and collagen within the AAA wall. Linear regression models were used to correlate geometrical, mechanical, and mass fraction data with maximum AAA diameter. RESULTS: Both ILT thickness and AAA expansion rate increased and were positively correlated with maximum AAA diameter, while there was a slight increase in wall thickness for AAAs with a larger maximum diameter. For the biaxial mechanical responses, mean peak stretches and maximum tangential moduli in the circumferential and longitudinal axes did not correlate with maximum AAA diameters. However, the quantified energy to propagate tissue dissections within intima-media composites showed a significant inverse correlation with maximum AAA diameter. Elastin content decreased significantly with increasing AAA diameter. CONCLUSION: Larger AAA diameters are associated with thicker ILTs, higher AAA expansion rates, and pronounced elastin loss, and may also lead to a higher propensity for tissue dissection and aneurysm rupture.

Paraganglioma of the carotid body: treatment strategy and SDH-gene mutations.

OBJECTIVES: The aim of the present study was to review treatment results in patients with paraganglioma (PGL) of the neck presenting as carotid body tumour, long-term follow-up and relevance of genetic testing for succinate dehydrogenase (SDH)-gene mutations. DESIGN: Retrospective analysis of prospectively collected data and prospective genetic analysis. MATERIALS AND METHODS: Over a 25-year period (1987-2011) 50 patients were operated for 63 PGLs of the neck. Pre-, intra- and postoperative findings were analysed. Sanger sequencing was performed for genetic testing of SDH-gene mutations (SDH B, SDHC and SDHD). RESULTS: Fifty patients underwent resection of 63 PGLs (62 benign, one malignant) without mortality. Eight patients underwent preoperative embolisation. Vascular surgical procedures were required in 15 operations (15/63 = 23.8%). Nerve lesions occurred after 13 operations (13/63 = 20.6%) and were associated with large tumours. A total of 44 patients are alive after a mean follow-up of 9.8 years. In 40 patients 17 SDH-gene mutations were detected (17/40 = 42.5%): 14 SDHD mutations, two SDHB mutations and one rare SDHC mutation. CONCLUSION: Surgery for PGL is recommended. All PGL patients should be screened for SDH mutations because it impacts the individual follow-up strategy. Whereas all PGL patients require annual ultrasound control, mutation carriers and family members with proven mutations should in addition be regularly examined by magnetic resonance imaging (MRI) of head, neck, thorax, abdomen and pelvis.

Gender differences in biomechanical properties, thrombus age, mass fraction and clinical factors of abdominal aortic aneurysms.

OBJECTIVE: The main purpose of the present study is the investigation of gender differences in the biomechanical properties, thrombus age, mass fraction and key clinical factors of abdominal aortic aneurysms (AAAs). MATERIALS AND METHODS: A total of 90 AAA samples (78 males and 12 females) were harvested from open surgical aneurysm repairs. Biaxial extension and peeling tests were performed to characterise the biaxial mechanical responses and to determine dissection properties of both the intraluminal thrombi (ILTs) and the thrombus-covered walls. Relative thrombus age was determined by characterising the ILT histological microstructure. Mass fraction analyses quantified dry weight percentages of elastin and collagen within the AAA walls. Moreover, we statistically compared clinical factors between male and female. RESULTS: The luminal layers of the female thrombi and the female AAA walls showed a significantly lower tissue stiffness (modulus) in the longitudinal direction when compared to males. Gender differences were also shown in the dissection properties of the intima-media composite within the AAA walls, in which a statistically significantly lower energy to propagate a dissection was quantified for females than for males. Moreover, 82% of female thrombi were relatively older (ILT age phases III and IV), twice that of male thrombi (43%). A pronounced lower elastin content was identified for the intima-media composites of male AAA walls, whereas female AAA walls had significantly lower dry weight percentages of collagen. Regarding clinical factors, nicotine pack years, serum creatinine and AAA expansion rate were found to be much higher for male patients. CONCLUSION: These findings may help to explain higher risks for AAA growth in males and the ruptures of smaller-sized AAAs in females.

Significant differences in functional outcome between upper and lower limbs after vascular trauma of the extremities.

BACKGROUND: This study aimed to compare the functional results between upper (UE) and lower extremity (LE) following arterial reconstruction due to vascular trauma. METHODS: Patients treated for arterial injuries with vascular reconstruction at two centres between 2005 and 2014 were assessed. The physical fitness questionnaire - Fitnessfragebogen (FFB-Mot) - was evaluated. The differences between pre- and post-traumatic values were compared statistically for UE and LE. Inability to return to the preoperative workplace or postoperative loss of at least 10% of the FFB-Mot were defined as the primary outcome events. RESULTS: Twenty-seven patients could be re-evaluated. The primary outcome event occurred in 52% (14/27) without significant difference between UE (43%) and LE (62%) (p = 0.45). The difference between the pre- and post-traumatic FFB-Mot scores showed a significantly poorer functional outcome after LE vascular injury (p = 0.012). CONCLUSION: Results indicate a poorer functional outcome after vascular extremity trauma to the LE than to the UE.

Effects of age on the elastic properties of the intraluminal thrombus and the thrombus-covered wall in abdominal aortic aneurysms: biaxial extension behaviour and material modelling.

OBJECTIVE: The intraluminal thrombus (ILT) present in the majority of abdominal aortic aneurysms (AAAs) plays an important role in aneurysm wall weakening. Studying the age-dependent elastic properties of the ILT and the thrombus-covered wall provides a better understanding of the potential effect of ILT on AAA remodelling. MATERIALS AND METHODS: A total of 43 AAA samples (mean age 67 ± 6 years) including ILT and AAA wall was harvested. Biaxial extension tests on the three individual ILT layers and the thrombus-covered wall were performed. Histological investigations of the thrombi were performed to determine four different age phases, and to correlate with the change in the mechanical properties. A three-dimensional material model was fitted to the experimental data. RESULTS: The luminal layers of the ILT exhibit anisotropic stress responses, whereas the medial and the abluminal layers are isotropic materials. The stresses at failure in the equibiaxial protocol continuously decrease from the luminal to the abluminal side, whereby cracks, mainly oriented along the longitudinal direction, can be observed in the ruptured luminal layers. The thrombi in the third and fourth phases contribute to wall weakening and to an increase of the mechanical anisotropy of their covered walls. The material models for the thrombi and the thrombus-covered walls are in excellent agreement with the experimental data. CONCLUSION: Our results suggest that thrombus age might be a potential predictor for the strength of the wall underneath the ILT and AAA rupture.

Long-term follow-up of vascular reconstructions after supracondylar humerus fracture with vascular lesion in childhood.

INTRODUCTION: Supracondylar humerus fractures in childhood present with a pulseless but well-perfused hand in 2.6% of cases and with limb-threatening ischaemia in <1%. Conservative treatment is widely used in non-limb-threatening ischaemia, in particular if the child is very young (<2.5 years). It has been sufficiently proven that conservative treatment may retard growth. The aim of our study was to determine long-term patency rates after surgical reconstruction and growth impairment, if any, after surgical vascular reconstruction. PATIENTS AND METHODS: Between June 1990 and June 2004, 12 children (mean age 6.6 years, eight boys and four girls) with supracondylar fracture with vascular lesions underwent surgical reconstruction at the Department of Vascular Surgery at the University Hospital, Graz. Patient files were reviewed retrospectively. All patients were recalled for physical (forearm length and volume) and ultrasonographic examinations (forearm blood flow) in 2005 and for ultrasonographic examinations (reconstructed vascular area) in 2011, with a final mean follow-up time of 14.0 years (range 6.8-20.9 years). RESULTS: Twelve patients, 10 of whom had undergone growth measurements in 2005, were available for the latter examination. All were doing well, with patent vascular reconstructions. Seven reconstructed brachial arteries were enlarged, two of which with intramural calcifications, four did not show abnormalities and one presented with 45% thinning. There were no differences between affected and healthy forearms concerning volume, length and blood flow. CONCLUSIONS: Our data emphasise that surgical reconstruction is effective in terms of blood supply and growth. In cases with interposition of greater saphenous vein or venous patch plasty, we found a high risk for development of enlargements. We suggest that these patients be followed periodically, with ultrasound studies, to detect aneurysms and/or thrombotic changes as early as possible.

Impact of Staphylococcus aureus protein A (spa) genetic typing in cases of prosthetic shunt graft infections.

INTRODUCTION: In January 2014 an internal audit was performed at the department of surgery, division of vascular surgery of the Medical University Graz, Austria, to assess the short and long-term outcomes of prosthetic shunt graft implantations performed between December 1998 and December 2013. A 10.8 % explantation rate due to graft infection was detected. The majority of the cases were associated with Staphylococcus aureus. The aim of this study was to clarify whether this constitutes a nosocomial problem. PATIENTS AND METHODS: Between December 1998 and December 2014 a total of 490 prosthetic shunt grafts were implanted. After exclusion of 54 cases, 436 shunts remained for statistical analysis. Genetic analysis (spa typing) was acquired from three new cases with involvement of S. aureus in 2014. The impact of several factors (e.g. sex, institute for dialysis, age, type of prosthesis, implantation surgeon and position of shunt) on the shunt graft infection rate was statistically analyzed. RESULTS: Of the prostheses 14.0 % (61 out of 436) had to be explanted of which 12.4 % (54/436) were due to infection. In 77.8 % (42/54) bacteria were found in blood and/or wound cultures. Staphylococcus aureus was present in 76.2 % (32/42) of the cases with detected bacteria and in all cases was sensitive to methicillin. The infection rate was not significantly dependent on any of the investigated factors; however, the factor "institute for dialysis" had a remarkable p­value of 0.060 with the infection rate ranging from 8.5 % to 18.2 % depending on the institution. Three different S. aureus protein A (spa) types were found: t015, t359, t6265. The detection of three different spa types means that these patients had different sources of S. aureus so that a nosocomial problem is very unlikely. CONCLUSION: Genetic typing of spa is a suitable technique for distinguishing between nosocomial and community acquired sources of prosthetic shunt graft infections.

A classification of cardiac allograft rejection. A modification of the classification by Billingham.

We herein propose a classification of rejection in cardiac allografts based on the original Stanford work. Our modified classification, as a work hypothesis, defines the following grades: mild acute rejection (A-1), corresponding to Billingham's "mild rejection"; mild acute rejection with probable conversion to moderate rejection (A-2); moderate acute rejection (A-3), comparable to Billingham's "moderate rejection"; and severe acute rejection (A-4), morphologically identical with the respective grade in the Billingham classification. The resolution of rejection has been classified into two grades--early (A-5a) and late (A-5b) resolution--according to the development of granulation tissues. We also grade the degree of vasculopathy (B-1, B-2) and chronic rejection (C), which is characterized by aggressive fibrosis and persistent vasculopathy. Mild rejection with possible conversion to moderate rejection is defined by an increasing quantity of retrogressive changes in myocytes. Changes not related to transplantation are characterized in our classification by descriptive diagnosis. The proposed classification was validated by 1 year of clinical experience and by the evaluation of possible prognostic aspects of the classification.

Bile duct injury as a part of diagnostic criteria for liver allograft rejection.

The decisive criterium of acute liver allograft rejection was found to be the presence of the diagnostic triad of acute rejection; ie, the presence of portal inflammatory mixed infiltrates, venous endothelialitis (both portal and central), and bile duct injury. On the basis of the presence of each of the components of the diagnostic triad, criteria for the diagnosis of different degrees of acute rejection were developed, particularly focusing attention on a detailed analysis of bile duct injury. Bile duct injury was shown to be an essential part of the histopathologic changes in all grades of acute rejection in the liver allograft, the grade of severity of bile duct injury correlating to a certain extent with the grade of severity of acute rejection. Our analyses have made it evident that bile duct injury, which most probably occurs earlier in the process of acute rejection than endothelialitis, is a more sensitive parameter than endothelialitis in the diagnosis of acute rejection. Furthermore, our analyses have revealed that bile duct injury in acute rejection is likely to be an irreversible process, depending on the number of episodes of acute rejection that previously occurred. On the other hand, it has become clear from our results that bile duct injury must not be considered to be an absolute histopathologic marker of acute rejection; however, it does have to be judged synoptically in connection with the other components of the diagnostic triad and the changes that the triad cause in the hepatic parenchyma. Additional analyses of the grade of severity of cholostases have shown that the cholostases are, to a certain degree, an accompanying phenomenon of the histopathologic changes characterizing acute rejection rather than a histopathologic change that is as significant as the presence of the components of the diagnostic triad.

Multidrug resistance in heart transplant patients: a preliminary communication on a possible mechanism of therapy-resistant rejection.

Multidrug resistance refers to a complex cellular phenotype, the hallmark of which is cross-resistance to multiple drugs, for example, chemotherapeutic agents, that are unrelated to the selecting agent in structure, cellular target, and mode of action. The expression of this multidrug resistance is connected with the overexpression of P-glycoprotein. By applying the method of immunocytochemical assay, we have demonstrated the appearance of the multidrug-resistant phenotype (P-glycoprotein+ cells, multidrug-resistant cells) in mononuclear cells of the peripheral blood from 32/49 patients receiving triple-drug (azathioprine, steroids, cyclosporine) immunosuppressive therapy after heart transplantation. In the group of patients showing not only the presence of cells with multidrug-resistant phenotype in the peripheral blood, but also a significant increase in the number of these cells during the interval of observation (0 to 767 days)-16/32/49 cases--a significantly increased incidence of acute rejection episodes could be demonstrated. This supports the hypothesis of a possible existence of a therapy-resistant form of acute rejection, with an involvement of mechanisms of multidrug-resistance playing a role in its causal development.

Reliable noninvasive rejection diagnosis after heart transplantation in childhood.

Rejection diagnosis was exclusively handled with noninvasive techniques in 16 children (mean age, 8.6 +/- 5.7 years; range, 0.9 to 15.2 years) over a total follow-up period of 18.3 patient years. No endomyocardial biopsies were performed. Intramyocardial electrogram recordings and echocardiographic investigations were used as two noninvasive techniques for rejection diagnosis. Daily noninvasive telemetric monitoring of the overnight intramyocardial electrogram was the major diagnostic guideline. The intramyocardial electrogram signal of the sleeping child was transmitted to a bedside receiver by an implanted telemetric pacemaker. The QRS amplitude was automatically analyzed and transferred to the in-hospital computer via a telephone modem connection. Rejection was diagnosed when QRS amplitude fell more than 8% below average baseline levels for 3 successive days, which was the indication for hospital admission. Medical antirejection treatment was instituted only if echocardiography showed impaired early diastolic left ventricular relaxation concomitant with a QRS-amplitude loss. The echocardiographic criterion was a prolongation of the parameter Te (Te is defined as the time span between onset of diastole and peak relaxation velocity of left ventricular wall) by more than 10 milliseconds compared to previous intraindividual values. Survival after a mean follow-up time of 13.7 months (range, 2 to 57 months) is 100%. A total of 22 rejection episodes were treated. During the first 6 postoperative months, the incidence of rejection requiring treatment was 1.4 episodes per patient. In patients at home, distant monitoring detected 13 episodes of a significant QRS-amplitude drop, which led to hospital readmission. In eight children, echocardiography was likewise positive, and rejection treatment was instituted. One child with positive intramyocardial electrography received antirejection treatment because of clinical evidence of rejection, although echocardiography was negative. In three instances, systemic infection was associated with the QRS-voltage loss. In one child a reason for QRS-complex reduction could not be identified. One rejection episode was treated on the grounds of clinical signs and positive echocardiography without a significant QRS-voltage drop. We conclude that distant noninvasive rejection monitoring based on meticulous application of the techniques described is a safe procedure. Daily monitoring of QRS amplitude in patients at home is an excellent safeguard against overlooking significant rejection episodes. This is of special importance in infants and children, in whom routine endomyocardial biopsy cannot be performed. Distant overnight monitoring minimizes psychosocial disturbance during follow-up after heart transplantation.

Clinical heart transplantation without routine endomyocardial biopsy.

In a prospective clinical study, routine endomyocardial biopsy (EMB) for early detection of cardiac allograft rejection was replaced by two noninvasive diagnostic techniques. In 32 patients who underwent transplantation during a 6-month period, intramyocardial electrogram (IMEG) amplitude was recorded with the telemetry function of a dual-chamber pacemaker system. An amplitude decrease of more than 8% below the individual range of variability in overnight long-term recordings served as an indicator of rejection. A prolongation of the time interval Te--the time span between maximal posterior wall contraction and peak retraction velocity--of more than 20 msec was used as an additional indicator of rejection-related left ventricular dysfunction. For patient safety, routine EMBs were still performed but remained undisclosed to the transplantation team. The pathologist was asked to intervene in cases of discrepancies between biopsy results and medical decisions, but no such intervention was necessary. Twenty-seven rejection episodes were treated medically, of which 22 were diagnosed noninvasively. In four patients, EMB, ordered because noninvasive parameters remained inconclusive, led to medical treatment. No false negative IMEG results were observed. Retrospective correlation with rejection gave a 100% negative predictive value for IMEG and a 96.9% negative predictive value for echocardiographic diagnosis. We conclude that omission of a schedule of routine biopsies is justified, if the described techniques of IMEG and echocardiography are meticulously applied and indicate normal cardiac function. EMB remains indicated if noninvasive parameters are not conclusive or if false-positive IMEG results, which were observed in the presence of infection or arrhythmias, are suspected. The frequency of EMB can be reduced by 90%, compared to conventional routine biopsy schedules. Diagnostic safety is increased because the additional information gained from IMEG and echocardiography is helpful in the interpretation of EMBs.

Electric myocardial impedance registration in humoral rejection after heart transplantation.

BACKGROUND: Because of the absent lymphocyte infiltrate, humoral-mediated rejection after heart transplantation is not diagnosed by the usual staining technique (hematoxylin-eosin method) of the endomyocardial biopsy specimen. However, humoral rejection is characterized by a distinct myocardial edema caused by capillary leakage. Because tissue edema increases the electric myocardial impedance of the corresponding tissue compartment the electric myocardial impedance method should be able to detect these episodes more reliably than biopsy. METHODS: To evaluate this hypothesis eight DLA-matched beagle dogs were subjected to heterotopic neck heart transplantation after multiple sensitization by skin grafts of the heart donor. For electric myocardial impedance registrations rectangular impulses (wide 1 msec) were applied over two intramyocardial electrodes and the impulse response was registered. Day-to-day comparisons were made and an increase of electric myocardial impedance of 10% or more was used as an indicator of rejection. To assess the influence of edema caused by electrode implantation, cortisone administration, narcosis, ischemia, or reperfusion on the electric myocardial impedance, identical electrodes were implanted in the native hearts of five additional dogs via lateral thoracotomy. These animals each received 100 mg methylprednisolone between postoperative days 20 and 22 and underwent heterotopic neck heart transplantation on postoperative day 28 without previous sensitization (protocol 2). Electric myocardial impedance electrodes were also implanted in these allografts (protocol 3). After transplantation myocardial biopsies were done every 2 days and the samples graded according to the International Society for Heart and Lung Transplantation classification in all dogs. RESULTS: Despite triple-drug immunosuppression (cyclosporine A, prednisolone, azathioprine) humoral rejection developed in all sensitized dogs as established by immunofluorescent staining of myocardial biopsy samples and functional deterioration. All episodes were diagnosed by electric myocardial impedance (sensitivity 100%), whereas only in one case the biopsy specimen was positive (International Society for Heart and Lung Transplantation grade > 1) (sensitivity 12.5%). All eight episodes could be treated successfully, that is, myocardial performance and electric myocardial impedance showed an immediate and full recovery. During the first 12 days none of the nonsensitized dogs exhibited rejection. Protocol 2 indicated that narcosis and the administration of cortisone did not per se have an influence on electric myocardial impedance and the influence of electrode implantation was negligible. Contrarily, edema caused by ischemia and reperfusion during transplantation (protocols 1 and 3) led to a significant increase in electric myocardial impedance. However, after 2 days this edema had faded away such that it no longer disturbed rejection diagnosis. CONCLUSION: We conclude that the registration of the electric myocardial impedance diagnoses humoral rejection episodes after heart transplantation not only reliably but also early, that is, before the onset of irreversible graft damage.