Astrid Wilfing

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.

Comparison of Conventional Surgical versus Seldinger Technique Emergency Cricothyrotomy Performed by Inexperienced Clinicians

Background: Cricothyrotomy is the ultimate option for a patient with a life-threatening airway problem. Methods: The authors compared the first-time performance of surgical (group 1) versus Seldinger technique (group 2) cricothyrotomy in cadavers. Intensive care unit physicians (n = 20) performed each procedure on two adult human cadavers. Methods were compared with regard to ease of use and anatomy of the neck of the cadaver. Times to location of the cricothyroid membrane, to tracheal puncture, and to the first ventilation were recorded. Each participant was allowed only one attempt per procedure. A pathologist dissected the neck of each patient and assessed correctness of position of the tube and any injury inflicted. Subjective assessment of technique and cadaver on a visual analog scale from 1 (easiest) to 5 (worst) was conducted by the performer. Results: Age, height, and weight of the cadavers were not different. Subjective assessment of both methods (2.2 in group 1 vs. 2.4 in group 2) and anatomy of the cadavers (2.2 in group 1 vs. 2.4 in group 2) showed no statistically significant difference between both groups. Tracheal placement of the tube was achieved in 70% (n = 14) in group 1 versus 60% (n = 12) in group 2 (P value not significant). Five attempts in group 2 had to be aborted because of kinking of the guide wire. Time intervals (mean ± SD) were from start to location of the cricothyroid membrane 7 ± 9 s (group 1) versus 8 ± 7 s (group 2), to tracheal puncture 46 ± 37 s (group 1) versus 30 ± 28 s (group 2), and to first ventilation 102 ± 42 s (group 1) versus 100 ± 46 s (group 2) (P value not significant). Conclusions: The two methods showed equally poor performance.

High prevalence of hyperhomocysteinemia in critically ill patients.

Objective: To test the hypothesis that the prevalence of hyperhomocysteinemia is increased in critically ill patients and correlates with disease severity and mortality in these patients. Design: A prospective study. Setting: Three medical intensive care units at the University of Vienna Medical School serving both medical and surgical patients. Patients: All consecutive admissions (n = 56) during a period of 4 wks. A total of 112 age‐ and gender‐matched healthy individuals constituted the control group. Interventions: None. Measurements and Main Results: Blood samples were drawn within 24 hrs after admission for analysis of total homocysteine (tHcy), folate, vitamin B6 levels, and vitamin B12 levels as well as to identify the 677C→T polymorphism in the gene coding for the enzyme 5, 10‐methylenetetrahydrofolate reductase. Acute Physiology and Chronic Health Evaluation III scores at admission and 24 hrs after admission as well as 30‐day survival were documented in all patients. Hyperhomocysteinemia was more prevalent in critically ill patients (16.1%; 95% confidence interval, 7.6% to 28.3%) compared with age‐ and gender‐matched healthy individuals (5.4%; 95% confidence interval, 2.0% to 11.3%; chi‐square test; p = .022). There was no difference in tHcy plasma concentrations in the first 24 hrs after admission to an intensive care unit between survivors and nonsurvivors. The 5,10‐methylenetetrahydrofolate reductase 677C→T polymorphism had no influence on tHcy levels and survival of intensive care unit patients. Conclusions: The prevalence of hyperhomocysteinemia is increased in critically ill patients compared to age‐ and gender‐matched healthy individuals. The clinical significance of this finding remains to be determined.

Effects of type I-interferons on human thyroid epithelial cells derived from normal and tumour tissue

Long term interferon (IFN) therapy is frequently associated with side effects which affect the thyroid gland such as hypothyroidism and thyroiditis. We have therefore tested the ability of type I-IFNs to exert direct effects on primary cultures of human thyroid epithelial cells: (i) Type I-IFNs (IFN-α 2b and IFN-ω) inhibit cell proliferation as determined by [3H]thymidine incorporation with a half-maximal effect at ∼1 ng/ml (50 pM). Inhibition of cell growth is observed in cells derived from normal thyroid as well as neoplastic tissue (autonomous and non-secreting adenoma; follicular, papillary and anaplastic carcinoma). (ii) Over a similar concentration range, type I-IFNs suppressed thyroglobulin release by thyroid cells. (iii) IFN-α 2b stimulated surface expression of major histocompatibility class (MHC) I but not MHC II molecules, while IFN-γ enhanced the expression of both MHC I and MHC II molecules. This effect of IFN-γ, but not that of IFN-α 2b was antagonized by suramin. (iv) Incubation of thyroid cells with IFN-α 2b also resulted in increased cell surface levels of the intercellular adhesion molecule 1 (ICAM-1). These findings demonstrate that type I-IFNs directly affect thyroid function and explain related side effects of these cytokines. In addition, our results provide a rational basis for the possible use of type I-IFNs in the treatment of patients with advanced thyroid cancer for whom no therapeutic alternative exists.

Suramin affects human peripheral blood mononuclear cells in vitro: inhibition of T cell growth and modulation of cytokine secretion.

Suramin, a polyanionic compound, which has been in clinical use for the treatment of African trypanosomiasis for several decades, has recently been introduced in clinical oncology. Its effects on the immune system seemed therefore of interest. In the present study we tried to elucidate in vitro how suramin affected different functions of human peripheral blood mononuclear cells (PBMC). Suramin suppressed the proliferation of PBMC in response to various stimuli, including OKT3, phytohemagglutinin (PHA), phorbolmyristate-acetate (PMA) and ionomycin, purified protein derivate of Mycobacterium tuberculosis (PPD) and antibodies against CD2. It also inhibited the binding of monoclonal antibodies to T cell surface antigens. This effect was not dependent on the isotype of the antibody, but seemed to be highly epitope-specific. Among a panel of antibodies against one antigen, only a few were affected by the compound. Whereas the binding of Leu3a and OKT3 was for instance fully suppressed by suramin, OKT4 and Leu4 binding was only slightly affected. Suramin also decreased the expression of T cell surface molecules such as CD2, CD25 and CD4 in preactivated PBMC and had pronounced effects on cytokine production. Interestingly the compound had adverse regulatory effects on different cytokines. Whereas the secretion of interferon-gamma was completely suppressed by suramin, interleukin-2 (IL-2) and IL-4 production was stimulated. These results demonstrate that suramin affects T cell function in multiple different ways. This will have to be considered, when suramin is used in the treatment of cancer patients.

Prostaglandin E1 does not influence plasmatic coagulation, hepatic synthesis, or postoperative blood loss in patients after coronary-artery bypass grafting

Abstract Study Objective: To assess whether postoperatively administered prostaglandin E 1 (PGE 1 ) might prevent bleeding in patients after coronary artery bypass grafting (CABG). Design: Prospective, randomized, placebo-controlled trial. Setting: University-affiliated hospital. Patients: 49 patients scheduled for elective CABG surgery. Interventions: The PGE 1 group received intravenous PGE 1 up to 15 ng/kg/min for 72 hours after surgery, whereas the placebo group received isotonic saline for the same time period. Measurements and Main Results: Nine patients (4 in the PGE 1 group vs. 5 in the placebo group) had to be excluded because of hemodynamic instability, and 1 in the placebo group because of gastric bleeding. In the remaining 39 patients (20 vs. 19), no significant differences with regard to hemoglobin levels or platelet count could be observed. There was no significant difference between the groups concerning the amount of packed red blood cells, platelet concentrates, or fresh frozen plasma transfused. No significant differences could be observed regarding laboratory markers of coagulation activation or hepatic synthesis either. Conclusions: PGE 1 did not prevent coagulation disturbances and blood loss when administered postoperatively in patients undergoing CABG. The absence of these expected effects might be explained by the concomitant administration of acetylsalicylic acid, whose antiaggregatory acivity seems to exceed the effects of PGE 1 .

The Effects of Suramin on Human Adrenocortical Cells In Vitro: Suramin Inhibits Cortisol Secretion and Adrenocortical Cell Growth

Suramin, a polycyclic and polyanionic drug, has been successfully used in the therapy of inoperable adrenocortical cancer. The present study was undertaken to investigate the effects of suramin on normal human adrenocortical cells in primary monolayer cultures. The proliferation and the basal, as well as the adrenocorticotropin (ACTH)-stimulated, cortisol secretion of these cells were studied. The data show that suramin decreases basal, as well as ACTH-stimulated, cortisol secretion in a dose-dependent manner (P less than .05 from 300 mumol/L upward). At a suramin concentration of 3 mmol/L, cortisol secretion was inhibited by 70% +/- 4% in ACTH-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was also inhibited by suramin at concentrations from 300 mumol/L upward, maximal suppression (71% +/- 6%, P less than .01) being observed at a concentration of 10 mmol/L. Both inhibition of cortisol secretion and inhibition of adrenocortical cell proliferation were not due to toxicity of the compound, as could be shown by restimulation of cortisol secretion in suramin-treated cells with ACTH. Our results indicate that suramin exerts an inhibitory influence on the cortisol secretion and on the proliferation of normal human adrenocortical cells. Suramin may not only be useful in the treatment of adrenocortical cancer, but may also have an ameliorative effect on other malignant conditions with augmented steroid hormone production, resistant to conventional forms of therapy.