Brigitte Stoiser

Outcome and prognostic factors in critically ill cancer patients admitted to the intensive care unit

Objective: To assess survival in cancer patients admitted to an intensive care unit (ICU) with respect to the nature of malignancy, cause of ICU admittance, and course during ICU stay as well as to evaluate the prognostic value of the Acute Physiology and Chronic Health Evaluation (APACHE) III score. Design: Retrospective cohort study. Setting: ICU at a university cancer referral center. Patients: A total of 414 cancer patients admitted to the ICU during a period of 66 months. Interventions: None. Measurements: Charts of the patients were analyzed with respect to underlying disease, cause of admission, APACHE III score, need and duration of mechanical ventilation, neutropenia and development of septic shock, as well as ICU survival and survival after discharge. Mortality data were compared with two control groups: 1362 patients admitted to our ICU suffering from diseases other than cancer and 2,776 cancer patients not admitted to the ICU. Main Results: ICU survival was 53%, and 1‐yr survival was 23%. The 1‐yr mortality rate was significantly lower in both control groups. Patients admitted after bone marrow transplantation had the highest mortality. In a multivariate analysis, prognosis was negatively influenced by respiratory insufficiency, the need of mechanical ventilation, and development of septic shock during the ICU stay. Admission after cardiopulmonary resuscitation yielded high ICU mortality but a relatively good long‐term prognosis. Admission after surgery and as a result of acute hemorrhage was associated with a good prognosis. Age, neutropenia, and underlying disease did not influence outcome significantly. Admission APACHE III scores were significantly higher in nonsurvivors but failed to predict individual outcome satisfactorily. All patients with APACHE III scores of >80 died at the ICU. Conclusion: A combination of factors must be taken into account to estimate a critically ill cancer patients prognosis in the ICU. The APACHE III scoring system alone should not be used to make decisions about therapy prolongation. Admission to the ICU worsens the prognosis of a cancer patient substantially; however, as ICU mortality is 47%, comparable with severely ill noncancer patients, general reluctance to admit cancer patients to an ICU does not seem to be justified.

Influence of prothrombin complex concentrates on plasma coagulation in critically ill patients

Objective: To evaluate thrombogenicity of prothrombin complex concentrates (PCCs) in critically ill patients.¶Design: Prospective clinical study.¶Setting: Medical intensive care unit at a university hospital.¶Patients: 16 consecutive patients suffering from acquired deficiencies of coagulation factors and with either overt bleeding from any site or a planned invasive procedure.¶Interventions: 2000 factor IX units of PCCs intravenously.¶Measurements and results: Prothrombin time (PT), activated partial prothrombin time, fibrinogen, platelet count, plasma levels of coagulation factors II, V, VII, VIII, IX, X, antithrombin, protein C, thrombin-antithrombin complex (TAT), prothrombin fragment F1+2, and the fibrin degradation product D-dimer were measured prior to and 1, 3, and 24 h after administration of PCCs. PT as well as coagulation factors II, VII, IX, and X, TAT, and F1+2 showed a significant increase after administration of PCCs. All other parameters remained unchanged.¶Conclusions: Administration of PCCs induces thrombin generation. No evidence for induction of disseminated intravascular coagulation in biochemical terms could be found. When rapid correction of acquired coagulation factor disturbances is warranted, the use of PCCs seems reasonable, but the elevated risk of intravascular thrombus formation should be kept in mind.

Frequent development of lupus anticoagulants in critically ill patients treated under intensive care conditions.

Objective To investigate how often a prolongation of the activated partial thromboplastin time in critically ill patients is caused by lupus anticoagulants and to identify possible triggering events. Design Prospective study. Setting Internal medicine intensive care unit (University Hospital of Vienna, Vienna, Austria). Patients Fifty-one critically ill patients without severe coagulopathy, hepatopathy, or anticoagulant treatment (35 male, 16 female, median age 60 yrs, range: 22–85 yrs). Interventions All patients were screened daily for lupus anticoagulants with the activated partial thromboplastin time STA assay. Measurements and Main Results Diluted Russell’s viper venom time, plasma mixing studies, and confirmation assays were used to identify lupus anticoagulants at the time of an unexplained prolongation of the activated partial thromboplastin time. The influence of heparin was excluded by determination of thrombin clotting time and anti-Xa activity. In 27 of 51 patients (52.9 %) lupus anticoagulants were found after a median stay of 13 days. None of the patients had concomitant immune thrombocytopenia, hypoprothrombinemia, bleeding, or thromboembolic complications. Sepsis (p = .006) and/or catecholamine treatment (p = .002) were significantly associated with the development of lupus anticoagulants. Extracorporeal circulation, transfusion of blood products, or surgery did not increase this risk. Lupus anticoagulants resolved spontaneously in 63% of the patients after a median stay of 17 days. Conclusions Lupus anticoagulants are frequent in critically ill patients and associated with sepsis syndrome and/or catecholamine treatment. The prolonged activated partial thromboplastin time does not warrant the administration of coagulation factors or the cessation of anticoagulant therapy or prophylaxis, inasmuch as this phenomenon is not associated with bleeding or thromboembolic complications.

Influence of pentoxifylline on cytokine levels and inflammatory parameters in septic shock.

ObjectiveTo evaluate the influence of pentoxifylline (PTX), a phosphodiesterase inhibitor, on cytokines and inflammatory proteins in patients suffering from septic shock.DesignProspective study comparing a therapy group to a matched control group.SettingMedical intensive care unit at a university hospital.PatientsTwenty four patients fulfilling the criteria of septic shock were included in this study. Twelve patients received PTX (therapy group) and 12 patients matched for diagnosis, age and gender served as the control group.InterventionsPentoxifylline at 1 mg/kg per hour over 24 h in the therapy group.Measurements ad resultsCytokine levels [tumor necrosis factor-α (TNF)], soluble TNF receptor [TNF-R], and interleukin-6 [IL-6] and inflammatory proteins [C-reactive protein, α-1-antitrypsin (AAT), fibronectin, and haptoglobin], as well as hemodynamic parameters and the APACHE III score were evaluated before initiation of therapy and 24 h later. After 24 h, TNF levels were significantly lower in the therapy group (p=0.013), while IL-6 levels were significantly higher in the therapy group (p=0.030). Within the 24 h TNF declined significantly in the therapy group (p=0.006), while IL-6 showed a significant increase (p=0.043). AAT and the APACHE III score tended to differ significantly after 24 h between the groups [AAT levels higher in the therapy group (p=0.05), APACHE III score lower (p=0.05)]. In the therapy group, the systemic vascular resistance index was significantly higher after 24 h (p=0.0026) whereas the cardiac index declined (p=0.035).ConclusionsPTX does influence TNF levels in septic shock patients. Nevertheless, inhibiting a single mediator in severe septic shock cannot stop the inflammatory overreaction.

Ventilator-associated pneumonia: Increased bacterial counts in bronchoalveolar lavage by using urea as an endogenous marker of dilution.

Objective:Invasive diagnostic procedures such as bronchoalveolar lavage (BAL) with quantitative microbiological cultures are currently recommended for the diagnosis of nosocomial pneumonia. Commonly, in clinical practice, a threshold of ≥104 colony forming units/mL is used for therapeutic decisions. The use of these measurements in daily practice assumes that their repeatability is acceptable. However, many variations among the positive results have been noted. One of the most important is dilution of BAL, which may influence the quantitative results by minimizing bacterial counts. Knowledge of the extent of dilution may increase dramatically the value of quantitative cultures. The aim of this study was to determine to what extent specimens are diluted in BAL by measuring urea in BAL and blood. Furthermore, the impact of a potential dilution effect on the diagnosis of ventilator-associated pneumonia was studied. Patients and Setting:A total of 47 patients with ventilator-associated pneumonia in two medical intensive care units at the Vienna General Hospital, a university-affiliated facility. Design:Prospective study performed between January 2001 and July 2002. Methods:BAL fluid was divided immediately into two samples: one for direct microscopic examination of cytocentrifuge preparations for Gram staining to determine percentages of cells containing intracellular bacteria and one for quantitative cultures according to the Cumitech 7A guidelines. Epithelial lining fluid volume was calculated using urea as a marker of dilution and correlated with colony forming units per milliliter. Results:Nineteen out of 47 patients (40%) revealed significant bacterial growth (≥104 colony forming units/mL). Eight additional patients (17%) would have reached the cutoff level after correction of the dilution effect, which varied between 1.8- and 130-fold. Conclusions:Data suggest a great variation of dilution during BAL procedures, which influences quantitative results. Using urea to determine the dilution quotient could increase the value of bacterial thresholds in the diagnosis and therapeutic decision of ventilator-associated pneumonia.

Activation of endothelium by immunotherapy with interleukin-2 in patients with malignant disorders

Treatment with intravenous recombinant human interleukin‐2 (rh IL‐2) is frequently accompanied by the capillary leak syndrome and disturbances of the coagulation system. Although the exact mechanisms are still not fully understood, the involvement of the endothelium is proven. This investigation aimed to elucidate more precisely the role of the endothelium in the generation of IL‐2‐based side‐effects. In nine tumour patients receiving intravenous rh IL‐2, parameters characterizing endothelial cell activation as well as activation of the coagulation system were evaluated. A significant increase of the circulating endothelial leucocyte adhesion molecule‐1 (cELAM‐1) and the vasoconstrictor peptide endothelin‐1 (ET‐1) was observed (P < 0.05), indicating activation of endothelial cells. The simultaneous increase of tissue‐plasminogen activator and plasminogen activator inhibitor type‐1 during therapy (P < 0.05) corroborated this observation. A decrease in platelet count parallelled by an increase of fibrin degradation products, the prolongation of partial thromboplastin time, and the decrease of fibrinogen (P < 0.05) suggested the development of disseminated intravascular coagulation (DIC), induced by activated endothelium and intensified by transient hepatic failure. We concluded that activation of the endothelium mediated by IL‐2 was accompanied by a loss of endothelial integrity and capillary leak. The activated endothelium can trigger DIC via activation of the coagulation cascade. The increased ET‐1 might act as an endogenous counter‐regulator of the disadvantageous haemodynamic side‐effects induced by IL‐2.

Diagnostic validity of pulmonary artery catheterization for residents at an intensive care unit

OBJECTIVE To assess the amount of additional information provided by measurements derived from pulmonary artery catheter (PAC) use beyond that derived from clinical evaluation by intensive care residents. METHODS One hundred forty-nine consecutive patients undergoing right-heart catheterization were prospectively included in the study. Before inserting a PAC, physicians had to predict pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance index (SVRI), cardiac index (CI), mixed venous oxygen saturation (SvO2), oxygen delivery (DO2), oxygen consumption (VO2), and pulmonary shunt fraction (Qs/Qt) by selecting a given option on a questionnaire. Ranges of options were chosen to create clear clinical differences among them. RESULTS The correct value was predicted in a median of 50% of cases (range, 45-63%). PAP was predicted correctly in 55%, PCWP in 46%, SVRI in 63%, CI in 62%, SvO2 in 45%, DO2 in 45%, VO2 in 51%, and Qs/Qt in 51%. A significant difference was found between estimated and measured values for all parameters (p < 0.01). No significant differences were detected between more and less experienced physicians. There was no significant difference between estimated and measured values with respect to the different courses of intensive care unit admissions or the different indications for PAC insertion. CONCLUSION In a selected group of critically ill patients, the PAC adds valuable and clinically relevant information to clinical assessment in about 50% of cases. Its use should not be withheld in patients with unclear hemodynamic and metabolic profiles.

Efficacy and tolerability of non-invasive ventilation delivered via a newly developed helmet in immunosuppressed patients with acute respiratory failure

ZusammenfassungFragestellungÜberprüfung von Effizienz und Verträglichkeit eines neu entwickelten Helmes für die nicht-invasive Beatmung von Patienten mit akutem respiratorischem Versagen.Patienten und MethodenZehn immunsupprimierte Patienten mit akutem respiratorischem Versagen wurden an unserer Intensivstation aufgenommen und in die Studie eingeschlossen. Bei allen Patienten wurde eine nichtinvasive Beatmung mit dem neuen Helm durchgeführt. Arterielle Sauerstoffsättigung und subjektive Verträglichkeit wurden während der ersten 24 Stunden evaluiert.ErgebnisseAlle Patienten tolerierten die Beatmung mit dem neuen Helm sehr gut, es kam zu einer deutlichen Verbesserung der arteriellen Blutgaswerte. Zwei Patienten mussten aufgrund eines septischen Schocks endotracheal intubiert werden, 8 Patienten konnten von der nichtinvasiven Beatmung entwöhnt werden.ZusammenfassungDie nicht-invasive Beatmung mit Hilfe des neuen Helmes könnte im Vergleich zur endotrachealen Intubation und der nicht-invasiven Beatmung mittels Standard-Maske eine effektive und besser verträgliche Methode sein.SummaryObjectivesTo assess efficacy and tolerability of a newly developed helmet for the delivery of non-invasive ventilation in patients with acute respiratory failure.Patients and methodsTen consecutive immunocompromised patients with acute respiratory failure admitted to our intensive care unit were included in the study. The patients were equipped with the helmet and non-invasive ventilation (NIV) was performed. Oxygenation and tolerability were assessed during the first 24 hours of NIV.ResultsAll patients tolerated the helmet well and their oxygenation improved. Two patients developed septic shock and had to be endotracheally intubated during the study period, eight patients survived to be weaned from NIV.ConclusionsNIV delivered via the helmet is effective and may serve as a better tolerated alternative to endotracheal intubation and to NIV via a standard face mask.

Likelihood of Inadequate Treatment: A Novel Approach to Evaluating Drug‐Resistance Patterns

OBJECTIVE To provide a novel way to predict the likelihood that antibiotic therapy will result in prompt, adequate therapy on the basis of local microbiological data. DESIGN AND SETTING Prospective study conducted at 3 medical intensive care units at the Viennese General Hospital, a tertiary care medical university teaching hospital in Vienna, Austria. PATIENTS One hundred one patients who received mechanical ventilation and who met the criteria for having ventilator-associated pneumonia. DESIGN Fiberoptic bronchoscopic examination was performed, and bronchoalveolar samples were collected. Samples were analyzed immediately by a single technician. Minimum inhibitory concentrations were determined for imipenem, cephalosporins (cefepime and cefpirome), ciprofloxacin, and piperacillin-tazobactam, and drug resistance rates were calculated. These drug resistance rates were translated into the likelihood of inadequate therapy (LIT; the frequency of inadequately treated patients per antibiotic and drug-resistant strain), cumulative LIT (the cumulative frequency of inadequately treated patients), and syndrome-specific LIT. RESULTS Among the 101 bronchoalveolar samples, culture yielded significant (at least 1 x 10(4) colony-forming units per mL) polymicrobial findings for 34 and significant monomicrobial findings for 31; 36 culture results were negative. Of the isolates from patients with ventilator-associated pneumonia who had monomicrobial culture findings, 33% were gram-positive bacteria and 20% were gram-negative bacteria. LIT suggested that 1 of 2 patients was treated inadequately for Pseudomonas aeruginosa infection. The LIT for patients with ventilator-associated pneumonia revealed that the rank order of antibiotics for appropriate therapy was (1) imipenem, (2) cephalosporins, (3) ciprofloxacin, and (4) piperacillin-tazobactam. These calculations were based solely on microbiological data. CONCLUSIONS The novel ratio LIT may help clinicians use microbiological data on drug resistance to predict which antimicrobial agents will provide adequate therapy. In daily practice, this new approach may be helpful for choosing adequate antimicrobial therapy.

Decrease of circulating hematopoietic progenitor cells During interleukin-2 treatment is associated with an increase of vascular cell adhesion molecule-1, a critical molecule for progenitor cell adhesion.

Administration of interleukin-2 (IL-2) to cancer patients has been shown to transiently decrease the number of circulating hematopoietic progenitor cells, but the mechanism of this phenomenon is unknown. Recently, the interaction of vascular adhesion molecule-I (VCAM-I) with leukocyte very late antigen-4 (VLA-4) has been demonstrated to play a crucial role in the adhesion of progenitor cells to bone marrow stromal elements. Cytokine induced upregulation of VCAM-1 leads to increased binding of progenitor cells to stromal cells in vitro and inhibition of this interaction by monoclonal antibodies is associated with marked progenitor cell mobilisation in vivo. In the present study we serially determined peripheral blood progenitor cell numbers during IL-2 treatment (10 courses) in 6 cancer patients and determined in parallel levels of soluble VCAM-1 as a surrogate marker for the in vivo activation of this molecule. Our data indicate that continuous intravenous administration of IL-2 for 5 days leads to a marked decrease of circulating progenitor cells associated with a substantial increase of circulating VCAM-1. Circulating myeloid progenitor cells (CFU-GM) dropped from a mean value of 167 ± 187/ml pre IL-2 to 16 ± 15/ml on day 3 (p < 0.01). Similarily, mean erythroid progenitors (BFU-E) decreased from 282 ± 204/ml before IL-2 administration to 86 ± 61/ml on day 3 (p < 0.005). In contrast, soluble VCAM-1 rose from a mean value of 1814 ± 451 ng/ml before to 4607 ± 736 ng/ml at the end of IL-2 therapy (p < 0.0001). Sera from IL-2 treated patients did not inhibit hematopoietic colony formation from normal bone marrow. These results suggest redistribution and increased adhesion of progenitor cells to stromal and/or endothelial elements during IL-2 via the VCAM-I/VLA-4 interaction as a possible mechanism for the decrease of circulating progenitor cells during IL-2 therapy.