Effects of a clinical pathway 3 years after implementation in breast surgery.

PURPOSE: The aim of the present study is to evaluate the effects of the implementation of clinical pathways into routine practice of breast surgery. MATERIALS AND METHODS: We implemented a clinical pathway for breast surgery in 2006 and analysed for the following 3 years its path in respect to hospital stay, total costs per case, readmission rate, and patients' satisfaction. RESULTS: The mean hospital stay decreased significantly from 4.5 days in 2006 to 3.7 days in 2007 and revealed 3.4 days in 2008. This is a decrease by 24.4% for the duration of hospital stay. The total cost per case between 2006 and 2007 showed a significant decrease of 23.4%. The total costs increased by 13.4% in 2008. Readmission rate was under 5% and remained constant. Patients' satisfaction remained constant, whereby more than 90% of the expected good results were attained. CONCLUSIONS: There is substantial evidence that clinical pathways lead to various improvements in clinical care in surgery. We show a constantly significant effect on duration of hospital stay without any increase in the number of readmissions. In our view, it is not only an economic benefit which prevails here, but also especially a transparency of treatment which leads to higher compliance, better outcome and a shorter length of stay.

Home seeking behavior in rat pups: Attachment vs. kin selection, oxytocin vs. vasopressin.

We are interested in the rat as an animal model for infant-mother attachment. In the first experiment we tried to distinguish between a preference for familiar animals (attachment theory) and a preference for genetically related animals (kin selection theory) with the use of an early cross-fostering procedure. Genetic relationships did not influence preferences in cross-fostered pups on postnatal day 17, only familiarity did. Subsequently we investigated if peptides known to influence affiliative behaviors were also effective in the present paradigm. Injection of oxytocin into the cisterna magna did not yield significant effects on preference, while vasopressin and desglycinamide-[Arg8]vasopressin reduced the preference in a dose dependent manner. The effect of vasopressin was completely blocked by pretreatment with the vasopressin V(1A) receptor antagonist d(CH2)5Tyr(Me)(2),Arg(8)-vasopressin. We discuss the explanatory power of attachment theory and kin selection theory with regard to preference experiments in rats and the usefulness of the rat as an animal model for infant-mother attachment.

Recombinant activated factor VII for treatment of refractory hemorrhage after surgery for acute aortic dissection.

Despite appropriate treatment, surgery for aortic dissection is frequently associated with bleeding problems. In these series we report on the employment of recombinant activated factor VII (rFVIIa) for refractory hemorrhage after emergency surgery for acute type A aortic dissection, used to face the problems of postoperative blood loss and transfusion requirements. Despite the good results of the therapy, a patient presented with thrombosis of the left cavernous sinus. Although a risk of thromboembolic complications has to be considered, rFVIIa is a reasonable rescue option in life-threatening hemorrhage and enlarges our hemostatic armamentarium in surgery for acute aortic dissection.

Impact of combined C1 esterase inhibitor/coagulation factor XIII or N-acetylcysteine/tirilazad mesylate administration on leucocyte adherence and cytokine release in experimental endotoxaemia.

We determined the effects of combinations of C1 esterase inhibitor (C1-INH) with factor XIII and of N-acetylcysteine (NAC) with tirilazad mesylate (TM) during lipo-polysaccharide (LPS)-induced endotoxaemia in rats. Forty Wistar rats were divided into four groups: the control (CON) group received no LPS; the LPS, C1-INH + factor XIII and NAC + TM groups received endotoxin infusions (5 mg/kg per h). After 30 min of endotoxaemia, 100 U/kg C1-INH + 50 U/kg factor XIII was administered to the C1-INH + factor XIII group, and 150 mg/kg NAC + 10 mg/kg TM was administered in the NAC + TM group. Administration of C1-INH + factor XIII and NAC + TM both resulted in reduced leucocyte adherence and reduced levels of interleukin-1beta (IL-1beta). The LPS-induced increase in IL-6 levels was amplified by both drug combinations. There was no significant effect on mesenteric plasma extravasation. In conclusion, the administration of C1-INH + factor XIII and NAC + TM reduced endothelial leucocyte adherence and IL-1beta plasma levels, but increased IL-6 levels.

Effects of N-acetylcysteine and tirilazad mesylate on intestinal functional capillary density, leukocyte adherence, mesenteric plasma extravasation and cytokine levels in experimental endotoxemia in rats.

INTRODUCTION: The study's objective was to determine the effects of the administration of N-acetylcysteine (NAC) and of tirilazad mesylate (TM) on intestinal functional capillary density, mesenteric plasma extravasation, leukocyte adherence and on cytokine release during experimental endotoxemia in rats. METHODS: In a prospective, randomized, controlled animal study, 80 male Wistar rats were examined in 2 test series. Both series were divided into 4 groups. Group 1 served as control group (CON group). Group 2 (LPS group), group 3 (NAC group) and group 4 (TM group) received endotoxin infusions (10 mg/kg over 2 h). In NAC group 150 mg/kg body weight NAC was administered after the first 30 minutes of endotoxemia intravenously. In TM group, 10 mg/kg body weight TM was administered after the first 30 minutes of endotoxemia intravenously. Animals of the series 1 underwent studies of leukocyte adherence on submucosal venular endothelium of the small bowel wall and intestinal functional capillary density (FCD) in the intestinal mucosa and the circular as well as the longitudinal muscle layer by intravital fluorescence microscopy (IVM). Plasma levels of interleukin 1beta (IL-1beta), interferone gamma (IFN-gamma) and soluble intercellular adhesion molecule1 (s-ICAM 1) as well as white blood cell count (WBC) were estimated. In the animals of the series 2 mesenteric plasma extravasation was determined by IVM and plasma levels of tumor necrosis factor alpha (TNF-alpha), IL-4, IL-6, IL-10 and malondialdehyde (MDA) were estimated. RESULTS: After LPS administration, FCD in the villi intestinales was unchanged and in the longitudinal muscularis layer it was increased. There was no effect of NAC or TM administration on FCD.Although the plasma extravasation was not significantly influenced by LPS administration, TM administration resulted in a lower plasma extravasation in the TM group compared to the other groups. After endotoxin challenge, the firmly adherence of leukocytes to vascular endothelium as a parameter of leukocyte activation in endotoxemia was increased but NAC or TM administration had no influence on leukocyte adherence. The plasma levels of IL-1beta, IL-6, IL-10, TNF-alpha, IFN-gamma and sICAM-1 were increased in the endotoxemic groups (LPS group, NAC group and TM group) and the WBC was decreased compared to controls. IL-4 levels were unchanged during observation period. Plasma MDA levels were not influenced by LPS administration compared to controls. The administration of NAC resulted in lower sICAM-1 and MDA levels compared to the LPS group. The IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma plasma levels were not influenced by NAC or TM administration. CONCLUSIONS: In this posttreatment sepsis model in rats, NAC administration resulted in lower sICAM-1 and MDA levels compared to the LPS treated animals. TM administration reduced the plasma extravasation in this model.

Renal dysfunction according to the ADQI-RIFLE system and clinical practice patterns after cardiac surgery in Germany.

AIM: The aim of this study was to determine the incidence of renal dysfunction according to the Acute-Dialysis-Quality Initiative-(ADQI)-RIFLE grading system in cardiac surgery in Germany in 2003 and to determine if variations in the incidence of renal dysfunction are related to clinical practice patterns. DESIGN: prospective cohort analysis and practice pattern survey. MEASUREMENTS: 81 hospitals were requested to report prospectively sampled quality-management-data on patient load, case mix, aortic-cross-clamp-time, baseline and maximal plasma creatinine (CreaP), new-onset-renal-replacement-therapy, and clinical practice concerning the use of fluids, inotropic and vasopressor drugs, and diuretics. Fifty-one (63%) centers answered the survey. Twenty-six centers (32%)(representative for 29 623 patients(reported creatinine data. RESULTS: The incidence of a 50%, 100%, or 150% increase in plasma creatinine (graded as risk, injury, and failure according to the ADQI-RIFLE-system) were 9% (2-40%), 5% (0.8-30%), and 2% (0.6-33%), respectively, overall 15.4% (3.1-75%). The incidence of new-onset renal-replacement-therapy was 4.5% (0.6-24%). Centers with a low incidence of renal dysfunction 8.7% (3.1-15.4%)differed from those with a high incidence 51% (15.7-75%)by being more liberal with fluids, not preferring dopamine in ''renal'' or inotropic doses, and preferring noradrenaline as a vasopressor (all: P<0.05), but not by case mix, frequency of urgent or emergency cases, and the use of loop diuretics. CONCLUSIONS: Renal dysfunction is a frequent complication following cardiac surgery in many German heart centers. The variance between centers may not be explained by patient heterogeneity and may be related to different strategies regarding fluid therapy and the use of inotropes and vasopressors.

Intensive care unit stay of more than 14 days after cardiac surgery is associated with non-cardiac organ failure.

Some studies have shown an association between a prolonged intensive care unit (ICU) stay and risk factors such as mediastinal re-exploration, advanced age, low ejection fraction, lung disease and organ failure. The aim of this retrospective study was first to evaluate peri-operative risk factors (n = 2683) and secondly to evaluate long-term survival (n = 2563) in cardiac surgery patients with an ICU stay > 14 days. Long-term survival was assessed in an observational 3-year follow-up study. An ICU stay of > 14 days was associated independently with respiratory failure and dialysis-dependent acute renal failure, and with a significantly lower survival rate. Since an ICU stay is associated with a higher hospital and long-term mortality, measures should be taken throughout the entire hospital stay to identify and reduce the risk of organ failure.

Aspirin and clopidogrel taken until 2 days prior to coronary artery bypass graft surgery is associated with increased postoperative drainage loss.

OBJECTIVE: Platelet aggregation inhibitors, such as aspirin and clopidogrel, are associated with increased bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. We investigated the impact of time between the last intake of aspirin and clopidogrel before CABG surgery and drainage loss, transfusion requirements and rate of reoperation. PATIENTS AND METHODS: The records of patients who had coronary artery bypass graft surgery (CABG) were reviewed for intake of aspirin and clopidogrel within 7 days prior to surgery. Drainage loss, transfusion requirements and rate of reoperation for bleeding within 5 days after the operation, were recorded. RESULTS: Out of 261 analysed patients, 225 patients (86.2 %) had no anti-platelet medication and 36 patients (13.8 %) were on aspirin and clopidogrel. Aspirin and clopidogrel, taken all until 2 days prior to operation, were associated with a significantly higher postoperative blood loss (1840 mL [1230 - 3710] vs. 280 mL [185 - 765], p = 0.005 for one day and 850 mL [345 - 1725] vs. 277 mL [165 - 778], p = 0.026, for 2 days prior to surgery). The trend showed that patients in the study group received more platelet concentrates (PC: 5.3 % vs. 13.9 %, p = 0.067). The rate of reoperation for bleeding was not different ( p = 0.25). CONCLUSION: Aspirin and clopidogrel up to 2 days prior to CABG were associated with a significantly higher postoperative drainage loss.

Serotonergic functioning in children with oppositional defiant disorder: a sumatriptan challenge study.

BACKGROUND: Several studies support the notion that disturbances in the central serotonergic function are related to impulsive aggression. There is recent evidence from studies on 5-HT(1B) knock-out mice that this specific receptor is involved in impulsive aggressive behavior. The aim of the present study was to investigate 5-HT(1B/1D) receptor functioning in normal intelligent hospitalized children with oppositional defiant disorder (ODD). METHODS: The growth hormone (GH) response to a challenge with the 5-HT(1B/1D) agonist sumatriptan was examined in 20 children with an ODD, of whom 13 had an attention-deficit/hyperactivity disorder comorbidity, and 15 normal control subjects (NC). Blood samples for growth hormone were collected repeatedly between 8:30 and 12:00 AM. Sumatriptan was administered at 10 AM. The effect of stress due to this procedure was assessed by measuring salivary cortisol. RESULTS: The GH response was significantly stronger in the children with ODD. After sumatriptan injection NC children showed a significant increase in cortisol; no such pattern was present in the ODD group. CONCLUSIONS: The results suggest that the postsynaptic 5-HT(1B/1D) receptor is functionally more sensitive in children with ODD.

Neuropeptides involved in the pathophysiology of schizophrenia and major depression.

The present review summarizes the findings on the role of neuropeptides in the pathophysiology of schizophrenia and major depression. Several neuropeptides as vasopressin and endorphins in particular, beta-endorphin and gamma-type endorphins, cholecystokinin (CCK), neurotensin, somatostatin and Neuropeptide Y have been implicated in schizophrenia. During the last decade, however, few attempts to explore the significance of most of these and other neuropeptides in the pathophysiology of the disease or their therapeutic potential are found in the literature. An exception is neurotensin, which exerts neuroleptic-like effects in animal studies, while CSF, brain and blood studies are inconclusive. Things are different in major depression. Here much attention is paid to the endocrine abnormalities found in this disorder in particular the increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. Neuropeptides as corticotropin-releasing hormone (CRH), vasopressin and corticosteroids are implicated in the symptomatology of this disorder. As a consequence much work is going on investigating the influence of CRH and corticosteroid antagonists or inhibitors of the synthesis of corticosteroids as potential therapeutic agents. This review emphasizes the role of vasopressin in the increased activity of the HPA axis in major depression and suggests exploration of the influence of the now available non-peptidergic vasopressin orally active V1 antagonists.

Hirudin versus heparin for anticoagulation in continuous renal replacement therapy.

OBJECTIVE: To compare the efficacy and safety of hirudin and heparin for anticoagulation during continuous renal replacement therapy (CRRT) in critically ill patients. DESIGN: Prospective, randomized controlled pilot study. SETTING: Single centre; interdisciplinary intensive care unit at a university hospital. PATIENTS: Seventeen patients receiving CRRT. INTERVENTIONS: Patients were randomly allocated to two groups. Heparin group (nine patients): continuous administration of 250 IU/h heparin; dose was adjusted in 125 IU/h steps with a targeted activated clotting time (ACT) of 180-210 s. Hirudin group (eight patients): continuous infusion of 10 micrograms/kg/h hirudin, dose was adjusted in 2 micrograms/kg/h steps with a targeted ecarin clotting time (ECT) of 80-100 s. Observation time was 96 h. MEASUREMENTS AND MAIN RESULTS: Measured filter run patency and haemofiltration efficacy did not significantly differ between the two groups. Three bleeding complications were observed in the hirudin group, none in the heparin group (P < 0.01). At the onset of bleeding, which occurred 60 or more hours after the start of therapy, only one patient was still under continuous hirudin administration but levels were either in therapeutic range or below. CONCLUSIONS: Hirudin can be used efficiently for anticoagulation in CRRT. Late bleeding complications may have been caused by possible hirudin accumulation, but this was not evident from hirudin plasma and ECT levels. Since bleeding complications were observed only in the presence of documented coagulation disorders, not only adequate drug monitoring but also the plasmatic and cellular coagulation status of the patient should be taken into consideration for adjusting hirudin dosage.

Clinical features and outcome in 1076 patients with ruptured intracranial saccular aneurysms: a prospective consecutive study.

In a well-defined area, The Kingdom of Denmark, 1076 patients with ruptured intracranial aneurysms were admitted to the six Danish neurosurgical departments in a prospective consecutive study in the 5-year period 1978-1983. Follow-up examinations were accomplished 3 months and 2 years after the admission. A total of 674 women and 402 men with a median age of 49 years were included in the study. The localisation of the ruptured aneurysms were: internal carotid artery 285, anterior communicating artery and horizontal part of anterior cerebral artery 383, middle cerebral artery 291, basilar and vertebral arteries 83 and peripheral or other localisation 34. A significantly better outcome was seen in cases with internal carotid aneurysms compared to other localisations. 670 patients underwent operation. A highly significantly better outcome was found in operated versus non-operated patients in comparable clinical conditions. The advantage of microneurosurgery was well documented. Patients with vasospasm had a significantly worse outcome. Within the first 2 weeks a daily rebleeding rate from 0.2% to 2.1% was observed, and patients who rebled had a significantly worse outcome compared to patients, who did not rebleed. The overall outcome at 2-year follow-up was: normal 27.5%, mild dementia 15.8%, severe dementia 9.9%, vegetative 1.3% and mortality 45.5%.

Clinical features and outcome in 48 patients with unruptured intracranial saccular aneurysms: a prospective consecutive study.

During a 5-year period (1978-1983) the clinical features and operative morbidity/mortality were registered prospectively for all patients in Denmark with an unruptured symptomatic (27 patients) or incidental (21 patients) intracranial saccular aneurysm. A follow-up examination was performed 2 years after diagnosis of the aneurysm. Thirty symptomatic aneurysms in 27 patients most frequently involved the visual pathways or ocular motility (66%). The median diagnostic delay for patients with impaired visual acuity was 7 months but only 14 days for patients with impaired ocular motility. The localisation of the 30 symptomatic and 23 incidental aneurysms were: internal carotid artery (73% approximately 35%), anterior communicating artery (3% approximately 26%) and middle cerebral artery (7% approximately 35%). The diameters of 73% of the symptomatic aneurysms were greater than 10 mm, while the diameter of 74% of the incidental aneurysms were below 10 mm. The total operative morbidity and mortality were 15% and 4%, respectively. The mortality rate in the follow-up period was 10-11% mainly due to fatal bleeding from unoccluded aneurysms. In 21 survivors, a normal mental status was found in 43% and mild dementia was found in another 43%. The impaired visual acuity was unchanged in 67% of patients, while the ocular motility had normalised in 75%. A normal daily functional capacity was enjoyed by 57% while 43% had a moderate reduction, mostly due to visual disturbances.

Intraspinal arachnoiditis and hydrocephalus after lumbar myelography using methylglucamine iocarmate.

A 35 year old woman developed a severe meningeal reaction after lumbar myelography using the water-soluble contrast medium methylglucamine iocarmate. Three months after myelography the findings were a transverse spinal cord syndrome corresponding to the middle thoracic segments resulting from well developed leptomeningeal adhesions. This was combined with a noncommunicating hydrocephalus, probably the result of leptomeningeal fibrosis in the posterior fossa. After treatment with a ventriculoatrial shunt the patient is almost free of symptoms. A possible pathogenetic relationship between the contrast medium, the chronic leptomeningeal changes, and the symptoms of our patient is discussed on the basis of the literature.