[Characteristics of the fetal and infant respiratory system : What the pediatric anesthetist should know]. / Besonderheiten des fetalen und kindlichen Atmungssystems : Was der/die (Kinder­)Anästhesist*in wissen sollte.

Respiratory complications are the most frequent incidents in pediatric anesthesia after cardiac events. The pediatric respiratory physiology and airway anatomy are responsible for the particular respiratory vulnerability in this stage of life. This article explains the aspects of pulmonary embryogenesis relevant for anesthesia and their impact on the respiration of preterm infants and neonates. The respiratory distress syndrome and bronchopulmonary dysplasia are highlighted as well as the predisposition to apnea of preterm infants and neonates. Due to the anatomical characteristics, the low size ratios and the significantly shorter apnea tolerance, airway management in children frequently represents a challenge. This article gives useful assistance and provides an overview of formulas for calculating the appropriate tube size and depth of insertion. Finally, the pathophysiology and adequate treatment of laryngospasm are explained.

[Fetal and pediatric cardiovascular physiology : Things you should know as an (pediatric) anesthesiologist]. / Fetale und kindliche Herz-Kreislauf-Physiologie : Was der/die (Kinder­)Anästhesist*in wissen sollte.

Immediately after birth the physiology of the cardiovascular system of the neonate undergoes some significant changes. The first breaths in life and the inflation of the lungs lead to a considerable drop in pulmonary arterial resistance. This results in the closure of the foramen ovale and ductus arteriosus; however, during the first weeks of life a sharp rise in pulmonary vascular resistance caused by hypoxia, hypercapnia and excessive positive pressure ventilation can lead to the reopening of the ductus arteriosus. This may result in subsequent strain of the left heart. In order to anticipate the reopening of the ductus arteriosus, it is recommended to measure the saturation of peripheral oxygen not only preductal (right hand), but also postductal (feet).An excessive volume therapy should be avoided as the neonatal myocardium is hallmarked by low cardiac compliance, reduced contractility and reduced ventricular filling.Until now there is still no uniform definition of hypotension in pediatric patients. Blood pressure values that are measured in awake children or are derived from the 50% age percentile values can thus only be used as approximate values. In all cases it is mandatory to recognize and consistently treat hypotension during pediatric anesthesia in order to prevent postoperative organ damage, particularly of the brain.The transcranial measurement of cerebral regional oxygen saturation (c­rSO2) by means of near-infrared spectroscopy (NIRS) provides valuable information about regional tissue oxygenation of the brain. This enables conclusions about the state of the multifactorial cerebral perfusion to be drawn. In this way monitoring of the hypoxia sensitive cerebral tissue can be accomplished and should be used in premature infants and neonates. When measuring a baseline in awake patients, a 20% drop of c­rSO2 from this baseline should be challenged and treated if necessary.

Indications and Route of Hysterectomy for Benign Diseases. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry No. 015/070, April 2015)

Background: Official guideline "indications and methods of hysterectomy" to assign indications for the different methods published and coordinated by the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (OEGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). Besides vaginal and abdominal hysterectomy, three additional techniques have been implemented due to the introduction of laparoscopy. Organ-sparing alternatives were also integrated. Methods: The guideline group consisted of 26 experts from Germany, Austria and Switzerland. Recommendations were developed using a structured consensus process and independent moderation. A systematic literature search and quality appraisal of benefits and harms of the therapeutic alternatives for symptomatic fibroids, dysfunctional bleeding and adenomyosis was done through MEDLINE up to 6/2014 focusing on systematic reviews and meta-analysis. Results: All types of hysterectomy led in studies to high rates of patient satisfaction. If possible, vaginal instead of abdominal hysterectomy should preferably be done. If a vaginal hysterectomy is not feasible, the possibility of a laparoscopic hysterectomy should be considered. An abdominal hysterectomy should only be done with a special indication. Organ-sparing interventions also led to high patient satisfaction rates, but contain the risk of symptom recurrence. Conclusion: As an aim, patients should be enabled to choose that therapeutic intervention for their benign disease of the uterus that convenes best to them and their personal life situation.

A short-term follow-up of implant based breast reconstruction using a titanium-coated polypropylene mesh (TiLoop(®) Bra).

INTRODUCTION: A new approach for implant based breast reconstruction (IBBR) is the use of a titanium-coated polypropylene mesh (TCPM) as an alternative to acellular dermal matrix (ADM). This TCPM has a good biocompatibility and can be used similarly to ADM. The aim of this study is to discuss indications, limitations and complications of TCPM in IBBR. METHODS: A retrospective analysis of 42 patients undergoing immediate or delayed IBBR using a TCPM was performed. Primary endpoints were incidence of infection and expander/implant with mesh removal due to infected fluid collection or extrusion. RESULTS: In two patients, mild hematoma, seroma or infection occurred. Skin necrosis or capsular contraction was observed in one patient. Mesh explantation was needed in 3 cases. These events were higher among the first cases and in patients with postoperative skin infection (p = 0.003). CONCLUSION: In selected patients with adequate soft tissue cover TCPM seems to be a helpful tool for implant stabilization in terms of lateral stabilization and fixation of the musculus pectoralis major. In comparison to ADM, TCPM is cheaper and initial results are promising, but further follow-up data are necessary. In patients with poor soft tissue cover ADM should be used.

Re-excision Rates and Local Recurrence in Breast Cancer Patients Undergoing Breast Conserving Therapy.

Background: Controversy continues over the impact of re-excision (RE) on local recurrence (LR) in patients with invasive breast cancer. Patients and Methods: We investigated factors which could effect RE rates in patients undergoing breast-conserving or oncoplastic surgery. Between 2000 and 2003, 489 patients with stage pT1-pT2 or pN0/1 tumors were evaluated. 74 patients fulfilled the inclusion criteria. Patients were categorized into 3 groups: no RE (n = 25), RE during primary surgery (n = 28), and RE performed during secondary or even tertiary procedure (n = 21). All tumor slides were re-evaluated by a pathologist specializing in breast cancer. Results: Mean follow-up was 70 months with an overall LR rate of 4.1 %. Binary logistic regression revealed no tumor-specific risk factors for RE. There was no LR in the group of patients who did not have RE. There was one case of LR in the group of patients who had RE during primary surgery. Two cases of LR were observed in the group of patients who had two or more surgical procedures. Conclusion: New risk factors for increased RE rates were not observed, reflecting the inconsistent data on risk factors for RE. However, breast cancers should be excised in a single procedure and oncoplastic procedures should be considered.

Effect of aliskiren, an oral direct renin inhibitor, on the pharmacokinetics and pharmacodynamics of a single dose of acenocoumarol in healthy volunteers.

OBJECTIVE: Aliskiren is a direct renin inhibitor approved for the treatment of hypertension. This study investigated the effects of aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of acenocoumarol in healthy volunteers. METHODS: This two-sequence, two-period, randomized, double-blind crossover study recruited 18 healthy subjects (ages 18-45) to receive either aliskiren 300 mg or placebo once daily on days 1-10 of each treatment period and a single dose of acenocoumarol 10 mg on day 8. Treatment periods were separated by a 10-day washout. Blood samples were taken frequently for determination of steady-state plasma concentrations of aliskiren (LC-MS/MS) and of R(+)- and S(-)-acenocoumarol (HPLC-UV), prothrombin time (PT) and international normalized ratio (INR). RESULTS: Co-administration with aliskiren had no effect on exposure to R(+)-acenocoumarol. Geometric mean ratios (GMR; aliskiren:placebo co-administration) for R(+)-acenocoumarol AUC(0-t) and C(max) were 1.08 and 1.04, respectively, with 90% CI within the range 0.80-1.25. Co-administration of aliskiren resulted in a 19% increase in S(-)-acenocoumarol AUC(0-t) (GMR 1.19; 90% CI 0.92, 1.54) and a 9% increase in C(max) (GMR 1.09; 90% CI 0.88, 1.34). The anticoagulant effect of acenocoumarol was not affected by co-administration of aliskiren. Geometric mean ratios were 1.01 for all pharmacodynamic parameters (AUC(PT), PT(max), AUC(INR) and INR(max)), with 90% CI within the range 0.97-1.05. CONCLUSION: Aliskiren has no clinically relevant effect on the pharmacokinetics or pharmacodynamic effects of a single dose of acenocoumarol in healthy volunteers, hence no dosage adjustment of acenocoumarol is likely to be required during co-administration with aliskiren.

A study of dose-proportionality in the pharmacokinetics of the oral direct renin inhibitor aliskiren in healthy subjects.

OBJECTIVE: To evaluate the dose-proportionality of the pharmacokinetics of aliskiren, the first in a new class of orally active direct renin inhibitors approved for the treatment of hypertension. METHODS: This was an open-label, single-center, single-dose, randomized, 4-period crossover study. Following a 21-day screening period, 32 healthy male or female subjects (ages 18 - 45 years) were randomized to 1 of 4 aliskiren dosing sequence groups (8 subjects per group): 75, 150, 300 and 600 mg. Blood samples were obtained for determination of plasma aliskiren concentrations (HPLC/MS/MS) for 96 h post dose. Log-transformed pharmacokinetic parameters AUC and C(max) were analyzed to determine dose-proportionality using the power model, parameter = A*(Dose)(beta), where A = intercept and beta = dose-proportionality coefficient. The predefined dose-proportionality criteria over the dose range 75 â 600 mg were 90% confidence intervals (CI) for beta contained within the range 0.89 - 1.11. RESULTS: AUC and Cmax values increased with increasing doses of aliskiren. Both AUC and C(max) were associated with high variability (coefficient of variation 55 - 64% for AUC and 59 - 117% for C(max)). The estimated proportionality coefficients (beta) for AUC(0-infiniti), AUC(0-t) and C(max) were 1.18 (90% CI 1.10, 1.25), 1.29 (90% CI 1.22, 1.36) and 1.42 (90% CI 1.31, 1.52), respectively. Dose-proportionality was, therefore, not demonstrated across the entire 8-fold dose range. For the clinical dose range of 150 â 300 mg, increases of 2.3- and 2.6-fold were observed for AUC and C(max), respectively. All doses of aliskiren were well tolerated. CONCLUSIONS: Exposure to aliskiren was greater than proportional over the dose range of 75 - 600 mg. Over the therapeutic dose range of 150 â 300 mg approved for the treatment of hypertension, AUC and Cmax increased by 2.3- and 2.6-fold, respectively. The pharmacokinetics of aliskiren show relatively high intersubject variability.

Monocyte phagocytosis of viable Staphylococcus aureus is impaired by barbiturates, but not by propofol.

BACKGROUND: Barbiturates and propofol are used for deep sedation of patients with elevated intracranial pressure refractory to standard therapeutic regimens. Such patients often suffer from bacterial infections, which are most commonly caused by Staphylococcus aureus. Various interactions of anesthetics with components of the host defense have been documented, but very little is known about the influence on monocytes, which are a first-line defense against bacterial invasion. Therefore, we studied the effects of thiopental, methohexital, and propofol on monocyte phagocytosis using an in vitro whole blood model of viable S. aureus. MATERIALS AND METHODS: Whole blood samples were preincubated with different concentrations of thiopental, methohexital, and propofol. Phagocytosis was stopped at different time points after addition of viable S. aureus. Monocytes then were stained with monoclonal antibodies for flow cytometric analysis of monocyte recruitment (ratio of ingesting monocytes). Furthermore, the fluorescence intensity of ingested bacteria served as semiquantitative measurement of phagocytosis activity. RESULTS: Both barbiturates inhibited monocyte recruitment and phagocytosis activity concentration-dependently, whereas propofol did not affect any of the investigated parameters. At concentrations of 7.6 x10(-3) M thiopental or 1.1 x 10(-3) M methohexital and greater, monocyte recruitment and phagocytosis activity were significantly inhibited. The calculated half-maximum inhibitory concentration (IC50) of thiopental was 8.4 x 10(-3) M for monocyte recruitment and 8.6 x 10(-3) M for phagocytosis activity. The corresponding values for methohexital were 4.1 x 10(-3) M and 1.1 x 10(-3) M, respectively. CONCLUSION: The two barbiturates induce concentration-dependent inhibition of monocyte phagocytosis, whereas propofol is without effect. In combination with previously described effects on granulocyte function, these findings suggest that defense against bacterial infection might be reduced by barbiturates.

Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of hypertension, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers.

Aliskiren is a novel, orally active direct renin inhibitor that lowers blood pressure alone and in combination with existing antihypertensive agents. As aliskiren does not affect cytochrome P450 enzyme activities, is minimally metabolised, and is not extensively protein bound, the potential for drug interactions is predicted to be low. Four open-label studies investigated the pharmacokinetic interactions between aliskiren 300 mg and the antihypertensive drugs amlodipine 10 mg (n = 18), valsartan 320 mg (n = 18), hydrochlorothiazide 25 mg (HCTZ, n = 22) and ramipril 10 mg (n = 17) in healthy subjects. In each study, subjects received multiple once-daily doses of aliskiren and the test antihypertensive drug alone or in combination in two dosing periods separated by a drug-free washout period. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry methods. At steady state, relatively small changes in exposure to aliskiren were observed when aliskiren was co-administered with amlodipine (AUC(tau) increased by 29%, p = 0.032), ramipril (C(max,ss) increased by 31%, p = 0.043), valsartan (AUC(tau) decreased by 26%, p = 0.002) and HCTZ (C(max,ss) decreased by 22%, p = 0.039). Co-administration with aliskiren resulted in small changes in exposure to ramipril (AUC(tau) increased by 22%, p = 0.002), valsartan (AUC(tau) decreased by 14%, p = 0.062) and HCTZ (AUC(tau) decreased by 10% and C(max,ss) by 26%, both p < 0.001). All other changes in pharmacokinetic parameters were also small, and not statistically significant. None of the observed pharmacokinetic changes was considered clinically relevant. Aliskiren inhibited plasma renin activity (PRA) and also prevented the reactive rise in PRA induced by valsartan. The most commonly reported adverse events were headache, dizziness and gastrointestinal symptoms (all mild in severity), which were similar in frequency during antihypertensive drug treatment alone and in combination with aliskiren except for an increase in dizziness during treatment with the combination of aliskiren and HCTZ. In conclusion, aliskiren shows no clinically relevant pharmacokinetic interactions and is generally well tolerated when administered in combination with amlodipine, valsartan, HCTZ or ramipril.

Rhabdomyolysis in an obese patient after total knee arthroplasty.

We report the case of a morbidly obese patient who developed rhabdomyolysis with acute renal failure, hepatic dysfunction, and an increase of cardiac troponin-1 after total knee arthroplasty. Postoperative rhabdomyolysis has a wide range of triggers and differential diagnoses that should be considered by the anaesthesiologist and surgeons. We would like to emphasize that morbidly obese patients have an increased risk of developing postoperative rhabdomyolysis potentially leading to life-threatening disease. Intensified postoperative observation seem justified in these patients.

Remifentanil or sufentanil for coronary surgery: comparison of postoperative respiratory impairment.

BACKGROUND AND OBJECTIVE: High-dose opioid anaesthesia contributes to decreasing metabolic and hormonal stress responses in patients undergoing cardiac surgery. However, the increase in context-sensitive half-life of opioids given as a high-dose regimen can affect postoperative respiratory recovery. In contrast, remifentanil can be given in high doses without prolonging context-sensitive half-life due to its rapid metabolism. Therefore, we performed a prospective, randomized trial to compare anaesthesia consisting of propofol/remifentanil or propofol/sufentanil with regard to postoperative respiratory function and outcome. METHODS: Patients undergoing coronary artery bypass grafting were randomized to a propofol/remifentanil (0.5-1.0 microg kg(-1) min(-1)) or propofol/sufentanil (30-40 ng kg(-1) min(-1)) based anaesthetic. Carbon dioxide response, forced expiratory volume in one second, vital capacity, and functional residual capacity were measured 1 day prior to the operation, 1 h before extubation, 1, 24 and 72 h after extubation. In addition, the incidence of atelectasis, pulmonary infiltrates, intensive care unit and postoperative length of stay were compared. Patients and physicians were blinded to the treatment group. RESULTS: Twenty-five patients in each treatment group completed the study. There was no difference between patients of the treatment groups regarding demographics, risk- or pain scores. In all patients, carbon dioxide response, forced expiratory volume in one second, vital capacity and functional residual capacity were decreased postoperatively compared to baseline. Patients randomized to remifentanil had less depression of carbon dioxide response, less atelectasis and shorter postoperative length of stay (12 d vs. 10 d) than after sufentanil (P < 0.05). CONCLUSIONS: Intraoperative use of high-dose remifentanil for coronary artery bypass grafting may be associated with improved recovery of pulmonary function and shorter postoperative hospital length of stay than sufentanil.

Breast cancer sagittal/horizontal plane location influences axillary lymph node involvement.

AIM: To assess the influence of tumour location on axillary lymph node involvement (ALNI) and prognosis in breast cancer by evaluating the significance of the sagittal/horizontal alignment. METHODS: We compared 57 patients with superficially located breast carcinomas up to 3.0 cm with patients having lesions in posterior planes of the breast. Both groups were matched according to age, time of diagnosis, tumour size, grade, hormonal receptor status and tumour site within the frontal plane. Histologic evidence of skin involvement, excluding tumours fulfilling the criteria for pT4b, was defined as inclusion criteria and reference plane for superficial tumour location. RESULTS: Tumours situated in the superficial region of the breast, compared to those located in deeper planes, have an increased risk of ALNI (p=0.023), whereas no difference was observed with reference to disease-specific survival (p=0.203). CONCLUSION: This study shows that ALNI is dependent on sagittal/horizontal as well as frontal tumour location. Clinicians should be aware that tumours lying posteriorly may be at increased risk of occult spread outside axillary lymph nodes.

Cardioprotection by aldosterone receptor antagonism in heart failure. Part I. The role of aldosterone in heart failure.

In recent years understanding of the role of aldosterone has expanded beyond the known classic effects of promoting renal sodium retention and potassium and magnesium loss. It is now well documented that aldosterone causes myocardial and perivascular fibrosis, blocks the myocardial uptake of norepinephrine, and increases plasminogen activator inhibitor levels. In conjunction with angiotensin II, aldosterone causes vascular damage, endothelial dysfunction, and decreased vascular compliance. Therefore, the renin-angiotensin-aldosterone system (RAAS) plays a major role in the development of both hypertension and heart failure and is therefore, a key target for therapeutic interventions. Commonly prescribed medications for control of hypertension and congestive heart failure are inhibitors of the RAAS, including angiotensin converting enzyme inhibitors (ACE-I) and Angiotensin II (A-II) receptor antagonists. There is a well-documented increase in aldosterone levels that occurs over several months during chronic treatment with an ACE-I or A-II receptor antagonist. Such suppression of circulating aldosterone however, is transient, as exemplified by the term "escape" used to describe the phenomenon. This rebound of aldosterone even occurs when patients receive both an ACE-I and A-II receptor antagonist. In addition, ACE-I and A-II receptor antagonists are less effective in controlling BP in the estimated 60% of hypertensive patients who are salt (volume) sensitive and more prone to hypertension-associated morbidity such as black patients and type 2 diabetics. Thus chronic and complete blockade of aldosterone action requires an aldosterone receptor antagonist. The "Randomized Aldactone Evaluation Study" (RALES) trial results in patients with severe heart failure NYHA class III or IV and a left ventricular ejection fraction of no more than 35 percent showed that administration of a sub-hemodynamic dose of spironolactone (25 mg a day) as an add on therapy to ACE-I plus standard treatment resulted in a significant mortality reduction due both to decreased death from progressive heart failure and sudden cardiac death. These findings support the pivotal role of aldosterone in the pathophysiology of progressive heart failure. Although it is an effective antialdosterone agent, widespread use of spironolactone in humans is limited by its tendency to produce undesirable sexual side effects. At standard doses, impotence and gynaecomastia can be induced in men, whereas pre-menopausal women may experience menstrual disturbances. Data on a selective aldosterone receptor antagonist, eplerenone, appear promising for the effective blockade of aldosterone and its harmful effects without the sexual disturbances of spironolactone. Recently Eplerenone was successfully introduced for the treatment of hypertension and heart failure. Growing number of experimental studies are finding a broader role for Aldosterone in driving the pathophysiology of both heart failure and hypertension. When added to conventional therapy aldosterone receptor blockers show benefits which are in addition to those conferred by ACE-I and/or AII receptor blockers.

Scope and significance of non-uniform classification practices in breast cancer with non-inflammatory skin involvement: a clinicopathologic study and an international survey.

BACKGROUND: The study evaluates the scope of non-uniform classification practices concerning breast carcinomas with non-inflammatory skin involvement. PATIENTS AND METHODS: We compared the clinical course of patients with histologically proven non-inflammatory skin involvement: 119 (65.4%) with clinically obvious 'classical' skin changes (Group A) and 63 (34.6%) with no or only discreet changes (Group B). A questionnaire was circulated to pathology departments in 24 countries to assess the practice concerning the placement of skin- involved breast carcinomas in the TNM classification. RESULTS: Patients in Group B showed a significantly better disease specific survival (P=0.0002). Eighty-six respondents (70.5%) of the survey preferred the 'histological view' and classified tumors with only histological proven skin involvement as T 4 b/stage IIIB. The opposing classification principle ('clinical view'), which dictates that T 4 b breast cancer is a clinical diagnosis and the classical signs must be present, was supported by 31 respondents (25.4%). CONCLUSIONS: A large number of breast cancer patients with non-inflammatory skin involvement are only histologically proven and show, compared with cases exhibiting the classical clinical signs, significant differences in clinical course and prognosis. In general, both subsets were aggregated in one T category/stage (T 4 b/IIIB). This results in a considerable distortion of the reported statistical data.

[Effects of reduced shear stress on inflammatory reactions in vitro. Effects of pathological flow conditions on leukocyte-endothelial interactions and monocyte tissue factor expression in human cell cultures]. / Einfluss verminderter Scherkräfte auf Entzündungsreaktionen in vitro Effekte pathologischer Strömungsbedingungen auf Leukozyten-Endothel-Interaktionen und monozytäre "Tissue-factor-Expression" in humanen Zellkulturen.

BACKGROUND: During malperfusion and inflammation leukocyte adhesion is common. The purpose of this study was to examine the effects of reduced shear stress on leukocyte-endothelial interactions and subsequent inflammatory reactions such as up-regulation of tissue factor. METHODS: Isolated neutrophils and monocytes were co-incubated with human umbilical venous endothelium at 0-3 dynes/cm(2) in a flow chamber. Adhesion and tissue factor expression on adherent leukocytes were examined at various flow conditions. RESULTS: At 2-3 dynes/cm(2) adhesion occurred only on TNFalpha-activated endothelium. Below 1 dyne/cm(2) similarly increased adhesion was also observed on non-activated endothelium. As was observed for leukocyte adhesion, these shear stress-dependent cell interactions also resulted in an up-regulation of tissue factor on adherent monocytes from non-activated co-cultures. CONCLUSION: Apart from additional activators of inflammation, reduced shear forces may directly contribute to inflammation.