[Monitoring of organ functions. Dysfunction of kidneys, liver, gastrointestinal tract, and coagulation]. / Monitoring von Organfunktionen. Dysfunktion von Niere, Leber, Gastrointestinaltrakt und Gerinnung.

Monitoring of organ function is one of the core tasks of intensive care medicine. Although various monitoring devices and parameters have already been established for some organs, there are no or only few conditionally useful parameters or scores available for the kidneys, liver, gastrointestinal tract, and blood coagulation. Therefore, specific biomarkers and scores as well as combinations of both are currently investigated for better monitoring of these organs. This article gives a critical overview of currently used as well as investigational biomarkers, tests and scores in general, and shows some examples of the implications for common diseases, clinical situations and constellations in the intensive care unit.

Ineffective off-label use of recombinant activated factor VII in a case of bone-marrow transplantation-related gastrointestinal bleeding.

BACKGROUND: For patients with a normal coagulation system, who experience serious bleeding, sound evidence for recombinant activated factor VII (rFVIIa) as an effective haemostatic agent is only scarcely available so far from controlled clinical trials. In systematic reviews on the clinical use of rFVIIa, treatment failures were only rarely reported. CASE PRESENTATION: We present a 45-year old, Caucasian male with persistent intestinal bleeding due to enterocolitis associated with cytomegalovirus infection and acute graft-versus-host-disease. He had received allogeneic peripheral blood stem cell transplantation from an unrelated HLA-identical donor because of chronic myelogenous leukaemia diagnosed two years earlier. Bleeding started at day 18 after transplantation with bloody diarrhea, which was treated with multiple transfusions of fresh frozen plasma, platelet, and red blood cell concentrates, and continued relentlessly, despite all efforts, including continued transfusions, high-dose prednisolone, broad antibiotic and antiviral coverage, and tranexamic acid. Recombinant FVIIa was started at boluses of 90-120 mug/kg every 4-8 hours. Despite more than 10 doses, recurrent severe bleeding progressed to refractory shock, multiorgan failure and death. CONCLUSIONS: Little can be concluded from single case reports of clinical improvement, because publication bias in favour of positive effects is likely. Our case suggests that rFVIIa is not a panacea, in particular for severe bleeding after bone-marrow transplantation. As long as rigorous, controlled studies or comprehensive registries are lacking, conventional interventions remain the standard of care in non-haemophilic patients with severe bleeding.

Intravascular large B-cell lymphoma with a fulminant clinical course: a case report with definite diagnosis post mortem.

A patient is described who presented with pancytopenia, splenomegaly and excessively elevated lactate dehydrogenase levels in concurrence with signs of extramedullary hematopoiesis. Although initially considered in the differential diagnostic spectrum, a highly aggressive lymphoma could not be identified before the patient died, 6 weeks after admission. Even an intensive diagnostic work-up including splenectomy and repeated bone marrow biopsies was inconclusive. Finally, the diagnosis of an intravascular large B-cell lymphoma, a highly aggressive clinical subtype of a diffuse large B-cell lymphoma, spreading within vascular structures of multiple organs was established by autopsy. Intravascular large B-cell lymphoma is often not diagnosed before death due to the exclusive intravascular growth pattern of the tumor cells and a fulminant clinical course. The heterogeneous clinical features of this lymphoma subtype are discussed.

Incidence and risk of potential adverse drug interactions in the emergency room.

OBJECTIVE: To determine the incidence and risk factors of potential adverse drug interactions occurring in patients in the emergency department. DESIGN: Survey of a random sample of medical records of elderly persons and other adults seeking care at an emergency department. The interactions were determined by a computer programme, reviewed using explicit criteria, and excluded if of uncertain or trivial clinical significance. SETTING: University Hospital Medical Emergency Department. PATIENTS: A total of 423 randomly selected adults seeking care at a university hospital emergency department. Attendances made by 195 persons over age 60 and 228 younger adults were evaluated. All subjects were treated on an outpatient basis. MAIN OUTCOME MEASURES: Seventy percent of attendances led to the prescription of an added medication. In 5.4% of the attendances in which at least one medication was added, the new medication introduced a potential adverse interaction. The number of medications used at attendance was the best predictor of whether a potential interaction would occur. Additional medications prescribed in the emergency department that accounted for most of the added interactions were theophylline, macrolid antibiotics, digitalis glycosides, nonsteroidal anti-inflammatory agents, angiotensin converting-enzyme inhibitors and calcium antagonists. CONCLUSIONS: Potential adverse drug interactions were more common in elderly patients because of the higher number of concurrent medications rather than age-based factors. Safeguards need to be introduced to prevent patients from receiving medications in the emergency departments that have the potential to cause adverse interactions.

Recombinant tissue plasminogen activator during cardiopulmonary resuscitation in 108 patients with out-of-hospital cardiac arrest.

BACKGROUND: Thrombolytic therapy during cardiopulmonary resuscitation (CPR) is a controversial issue in emergency medicine practice. This study was conducted to determine whether administration of recombinant tissue plasminogen activator (rt-PA) in out-of-hospital cardiac arrest of non-traumatic aetiology improves CPR outcome. METHODS AND RESULTS: A retrospective chart review of 401 patients with out-of-hospital cardiac arrest who were resuscitated by the emergency medical services (EMS) during a 6 year period was performed. A total of 108 patients received rt-PA during CPR and were compared to 216 controls, closely matched according to baseline characteristics, arrival status and ECG findings. Administration of rt-PA was optional. Return of spontaneous circulation (ROSC) occurred in 76 patients under rt-PA treatment (70.4 vs. 51.0% in controls; P=0.001). Fifty-two patients from the lysis group survived the first 24 h (48.1 vs. 32.9% in controls; P=0.003), while 27 (25.9%) survived to discharge. Autopsy reports revealed major bleeding complications in six patients receiving rt-PA treatment. Fulminant intracranial haemorrhage was observed in one patient who received rt-PA and in two cases from the control group. CONCLUSIONS: Thrombolytic therapy may improve frequency of return of spontaneous circulation substantially and increase primary survival in patients with non-traumatic cardiac arrest. Serious bleeding complications are not frequently observed under rt-PA treatment.

Hypersensitivity reactions associated with recombinant tissue-type plasminogen activator and urokinase.

Anaphylaxis or angioedema in response to recombinant tissue-type plasminogen activator or urokinase have been reported in only a few isolated cases. Both agents are endogenous proteins and thus considered non-antigenic. Activation of fibrinolysis may per se facilitate anaphylactoid reactions by pathophysiologic pathways that are not well understood. We report a unique case, review the literature and discuss implication for the clinician. The 25-year-old patient underwent thrombolytic treatment for extensive thrombosis of pelvic and deep lower extremity veins. The patient developed protracted anaphylactoid reactions during recombinant tissue-type plasminogen activator continuous intravenous infusion. After changing treatment to urokinase, the same symptoms recurred with more severe intensity, despite corticosteroid premedication. Symptoms resolved within hours after treatment with histamine receptor blockers. This unique observation, i.e. sequential occurrence of anaphylactoid reactions during recombinant tissue plasminogen activator and urokinase treatments, adds to existing evidence for an unspecific non-antigenic pathomechanism, and for a class effect of thrombolytics. Steroids do not prevent, but histamine receptor blockers seem to be an effective treatment of this unusual complication of thrombolytic therapy.

The inhibition of oxygen radical release from human neutrophils by resting platelets is reversed by administration of acetylsalicylic acid or clopidogrel.

Resting platelets inhibit oxygen radical release from neutrophils. Antiplatelet therapy may support this function by preventing platelet activation. Whether antiplatelet agents affect the antioxidative action of resting platelets in the absence of platelet activation is unknown. The effect of acetylsalicylic acid or clopidogrel administration on the antioxidative action of resting platelets was therefore studied in ten healthy volunteers. Preparations of resting platelets were obtained from 5 subjects each - before, during and after an eight-day course of daily treatment with 100 mg of acetylsalicylic acid or 75 mg of the thienopyridine clopidogrel. Human peripheral blood neutrophils were pretreated with the platelets at a ratio of (1/5)0 for 45 min; then formyl-Met-Leu-Phe-triggered oxygen radical release was measured fluorometrically. The inhibitory effect of platelets on oxygen radical release from neutrophils which was seen before treatment was abolished by antiplatelet therapy with either of the drugs, and inhibition was restored gradually after discontinuing acetlsalicylic acid/ clopidogrel intake. Results suggest that the protective role of resting platelets in controlling oxygen radical release from neutrophils in the absence of platelet activation may be impaired by antiplatelet therapy.

Plasma levels of procalcitonin and interleukin-6 in acute myocardial infarction.

Estimation of cardiac morbidity in patients after major surgery is a difficult problem. In addition, infectious complications seriously decrease potential beneficial outcome after cardiovascular surgery. The present study assessed the use of a newer marker of the inflammatory response, procalcitonin, in the field of myocardial infarction, in conjunction with measurements of interleukin-6. Forty-four consecutive cases with acute myocardial infarction were included in the study 4+/-1.3 h after the onset of symptoms. Plasma levels of procalcitonin and interleukin-6 were obtained at admission, and after 3, 6, 12, 18, 24 and 48 h, using commercially available test kits. The range of levels of interleukin-6 and procalcitonin was about normal at admission. Interleukin-6 levels increased significantly following myocardial infarction, whereas procalcitonin were essentially unchanged, i.e. remained close to the normal level threshold of 0.5 ng/ml; only minor variability occurred with a mean peak level of procalcitonin of 1+/-0.4 ng/ml. Data demonstrate that, in contrast to the acute phase reactant interleukin-6, plasma levels procalcitonin are not significantly elevated during uncomplicated acute myocardial infarction. This observation may support the role of procalcitonin measurements in the differential diagnosis of infectious and cardiovascular complications after major surgery.

Imported malaria: six cases of severe Plasmodium falciparum infection in Innsbruck, Austria, within a period of five weeks (February/March 1999)

Six patients (age, 30-76; 3 male, 3 female) with severe malaria tropica were admitted to the Department of Internal Medicine of the Innsbruck University Hospital within a time period of five weeks. All patients had recently visited classical malaria regions some days before admission: five patients the sub-Saharan Africa and one patient Thailand and Vietnam. All six patients had to be treated in the Intensive Care Unit. Three patients developed an acute respiratory distress syndrome. Two patients died of multi-organ failure. All six patients were treated with quinine and doxycycline intravenously. In one case, exchange transfusion was performed. Only two of six patients had taken prophylactic medication: one patient chloroquine and proguanil and the other mefloquine (she suffered from a severe gastroenteritis during the journey).

Thrombolytic therapy in adult meningococcal purpura fulminans with acute renal failure and severe perfusion deficits to the extremities.

OBJECTIVE: To investigate whether systemic administration of recombinant tissue plasminogen activator would improve organ perfusion in an adult patient with fulminant meningococcal disease. DESIGN: Descriptive case report. PATIENT: A 45-year-old female with meningococcal septic shock, purpura fulminans and multiple organ failure who was treated in an eight-bed medical intensive care unit of a University hospital. INTERVENTION: In addition to standard aggressive treatment, on each of three consecutive days the patient received recombinant tissue plasminogen activator infusions at a dose of 20 mg over 4 hrs. RESULTS: Urine output was recorded before, during, and after the recombinant tissue plasminogen activator infusions. In addition, the patient's peripheral perfusion status was documented by clinical assessment. The patient showed a dramatic improvement in urine output, as well as a perceived increase in skin perfusion after recombinant tissue plasminogen activator therapy. The amount of exogenous vasopressor and inotropic support required to maintain the patient's hemodynamic status also rapidly decreased. CONCLUSIONS: In this adult patient, recombinant tissue plasminogen activator therapy resulted in improved organ perfusion similar to that reported for paediatric patients. The findings indicate a need for controlled studies concerning the use of thrombolytics in severe meningococcal disease.

Septicaemia and endomyocarditis caused by Aerococcus urinae.

Aerococcus urinae, an uncommon urinary tract pathogen, was recently shown to cause septicaemia and endocarditis in a few patients in Denmark and the Netherlands. In Austria this is the first report of a fatal course of endomyocarditis by Aerococcus urinae, associated with multiple septic infarcts.