Heinz Burgmann

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.

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data

BACKGROUND Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each days delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each days delay). INTERPRETATION We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING F Hoffmann-La Roche.

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.

Evaluation of Seldinger technique Emergency cricothyroidotomy versus standard surgical cricothyroidotomy in 200 cadavers

Background: Percutaneous cricothyroidotomy is a lifesaving procedure for airway obstruction in trauma victims who need airway establishment and cannot be intubated or in whom intubation has failed. Methods: The purpose of this study was to examine whether there is a training effect using Seldinger technique emergency cricothyroidotomy (group 1; Arndt Emergency Cricothyroidotomy Catheter Set; Cook Critical Care, Bloomington, IN) versus standard surgical cricothyroidotomy (group 2). Twenty emergency physicians performed five cricothyroidotomies with each method in a total of 200 human cadavers, comparing efficacy and safety (speed, success rate, and injuries). Results: Seven attempts in group 1 and six in group 2 had to be aborted. Time intervals from the start of the procedure to location of the cricothyroid membrane were not significantly different between the groups. However, time to tracheal puncture (P < 0.01) and time to first ventilation (P < 0.001) were significantly longer in group 2. No time effect could be observed in both groups. The airway was accurately placed into the trachea through the cricothyroid membrane in 88.2% (82 of 93) of the cadavers in group 1 and in 84.0% (79 of 94) in group 2 (not significant). No injuries were observed in group 1, whereas there were six punctures of the thyroid vessels in group 2 (P < 0.05). Conclusions: With respect to time needed for the procedure, the participants performed Seldinger technique emergency cricothyroidotomy significantly faster as compared with standard surgical cricothyroidotomy. Even if no training effect had been observed, the authors believe that it is important to train residents in different methods of cricothyroidotomy in cadavers in addition to training in mannequins to achieve a higher level of efficacy in real-life situations. The shorter time to first ventilation and the fact that no injuries could be observed favor the Seldinger technique.

Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues

ABSTRACT Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. For this purpose fosfomycin concentrations in vivo in the fluid of the interstitial space of human soft tissues were measured by microdialysis following intravenous infusion of 4 or 8 g of fosfomycin (n = 6). Subsequently, bacterial isolates with relevance for soft tissue infections were exposed to concentrations according to the in vivo pharmacokinetic profile in the interstitial space fluid obtained by microdialysis. Our experiments indicated a high degree of soft tissue penetration for fosfomycin, with ratios of the area under the concentration-time curve from 0 to 8 h for muscle (AUC0–8muscle)/AUC0–8serumof 0.48 ± 0.08 and 0.53 ± 0.04 and ratios of AUC0–8adipose tissue/AUC0–8serum of 0.74 ± 0.12 and 0.71 ± 0.11 following administration of 4 and 8 g, respectively. In corresponding in vitro simulation experiments with selected isolates of Staphylococcus aureus,Enterobacter cloacae, and Serratia marcescensfor which MICs were 16 μg/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.

Anakinra in two adolescent female patients suffering from colchicine-resistant familial Mediterranean fever: effective but risky.

Sir, Mutations in the pyrin gene (MEFV) cause the inflammatory disorder familial Mediterranean fever (FMF) [1]. Most of the patients are treated with colchicine for the prevention of both attacks and secondary amyloidosis. Clinical failure of colchicine treatment is seen in 5 to 10% of patients. Patients who are non-responders suffer a lot despite taking painkillers. Quite often patients are unable to manage daily life because of the disease. No treatment recommendations exist for these cases [2]. Recently, two case reports concerning treatment of colchicine-resistant FMF patients with anakinra were published [3,4]. Anakinra is an interleukin-1 (Il-1) receptor antagonist. Il-1 is a major proinflammatory cytokine that is increased in activity by pyrin, which is shown to be elevated in FMF [5,6]. Since knowledge about the efficacy and tolerance of anakinra is rare we herein present two case studies of patients treated with it. Case 1: A 29-year old Turkish woman with positive personal and family FMF history was visiting our outpatient clinic in March 2007 because of recurrent FMF attacks associated with severe abdominal pain and fever. FMF was previously diagnosed in this patient in Turkey when she was 13 years of age. She had been taking colchicine tablets for several years but in the last year the attack rate had increased and she had typical symptoms every week. During the onset of symptoms she took a large amount of different painkillers, which had no effect. Despite an increased dosage of colchicine (1·5 mg d –1 ), she had elevated inflammation signs [C-reactive protein (CRP): 90·5 mg L –1 , normal: 0–10 mg L –1 ; serum amyloid A (SAA): 626 mg L –1 , normal: < 5 mg L –1 ]. Her serum creatinine level was 0·71 mg dL –1 and no proteinuria was detected. Because of her poor quality of life caused by the recurrent attacks we decided to try anakinra treatment. After informing the patient about the potential side effects and the empirical aspects of the therapy, treatment was started with 100 mg anakinra administered subcutaneously every day. Before administration a quantiFERON-TB Gold test was performed which showed a negative result. After eight days of anakinra treatment the patient was symptom free and after three weeks the inflammatory parameters almost normalised (Fig. 1). The administration of colchicine was not interrupted at any time point. Three weeks after the start of treatment, administration of anakinra was stopped because the patient was feeling well and it was assumed that continuing with colchicine would prolong the attack rate. After 4 days the patient came to our outpatient department again and was complaining of severe abdominal pain. The inflammation parameters were also elevated. Administration of anakrina was restarted and recovery was achieved within a few days concomitant with a decrease in the inflammation parameters. Colchicine was stopped at this time point since efficacy was missing. During the following 3 months an ‘on and off treatment’ with anakrina took place. The first time the application was stopped because the patient could not tolerate any further injections due to severe pain at the site of the injection. Her symptoms and inflammation parameters returned very quickly afterwards. The patient then decided to restart anakinra because the severity of her pain due to FMF persistently increased. Since the patient’s insurance company refused to pay for this treatment, anakinra therapy was stopped until this problem was resolved. Vienna General Hospital, Medical University of Vienna, Vienna, Austria (R. Gattringer, H. Lagler, K. B. Gattringer, S. Knapp, H. Burgmann, S. Winkler, W. Graninger, F. Thalhammer).

Experiences with severe P. falciparum malaria in the intensive care unit

Objective: To review the clinical profiles and therapies instituted for patients with severe malaria admitted to an ICU.¶Design: Retrospective study.¶Setting: Internal ICU of a tertiary care centre.¶Patients and participants: Between January, 1992, and February, 1999, 104 patients with malaria were admitted to the General Hospital of Vienna. Sixty-nine patients suffered from Plasmodium falciparum malaria (66 %), seven of these were admitted to the ICU.¶Measurement and results: Seven patients were admitted to the ICU, of whom three died (4 % in hospital case-fatality rate). Four patients required mechanical ventilation because of respiratory insufficiency and adult respiratory distress syndrome (ARDS), of whom three died. Three patients were treated with inhaled nitric oxide (NO) and kinetic therapy; one patient required extracorporeal veno-venous oxygenation. All patients who died required haemofiltration because of acute renal failure.¶Conclusion: As P. falciparum is a potentially life-threatening disease, reliable criteria for ICU admission should be defined and risk factors identified. Early ICU monitoring should be attempted, especially under the following conditions: (1) lack of clinical response to anti-malarial treatment within 48 h and/or (2) any signs of neurological disturbance (hypoglycaemia excluded). Prospective multicentre trials and guidelines for supportive intensive care are urgently needed.

Closed Suctioning System Reduces Cross-Contamination Between Bronchial System and Gastric Juices

In this prospective, randomized study, we evaluated whether a closed suctioning (CS) system (TrachCare) influences crossover contamination between bronchial system and gastric juices when compared with an open suctioning system (OS). The secondary aims were an analysis of the frequency of ventilator-associated pneumonia (VAP) and an analysis of alteration in gas exchange. Antibiograms were performed from tracheal secretions and gastric juice aspirates on Days 1 and 3 of intubation in 24 patients in a medical intensive care unit. Five cross-contaminations were observed in the OS group on Day 3 versus Day 1; the 5 strains shared common genotypes as determined by random amplification of polymorphic DNA. No cross-contaminations were seen in the CS group (P = 0.037). VAP occurred in 5 patients of the OS group but in none of the CS group patients (P = 0.037). Spao(2) decreased significantly in the OS group compared with presuctioning values--the opposite of the CS group. Whereas presuctioning values were comparable between groups, postsuctioning Spao(2) was significantly higher in the CS group. CS significantly reduced cross-contamination between bronchial system and gastric juices and reduced the incidence of VAP when compared with OS. Hypoxic phases can be reduced by the help of CS.

Decreased serum levels of TGF-β in patients with acutePlasmodium falciparum malaria

Apart from cellular immunity and immunopathology, various cytokines have been implicated in malaria-associated immunosuppression. In this study, serum levels of transforming growth factor-β (TGF-β) were determined with an enzyme-linked immunosorbent assay in 37 patients with acutePlasmodium falciparum malaria prior to, during, and after therapy and in 17 healthy controls in Bangkok, Thailand. Patients were treated with artesunate and mefloquine. TGF-β serum levels were found decreased prior to treatment (14±11 pg/ml versus 63±15 pg/ml in healthy controls;P<0.05). The serum concentrations of TGF-β increased after initiation of treatment and were within normal range on day 21. Serum levels of both tumor necrosis factor-ga (TNF-α) and soluble TNF-receptor 55 kDa were inversely correlated to serum levels of TGF-β (r= −0.667 andr=}-0.592, n=37; respectively,P < 0.05 for both). No correlation between parasitemia and serum levels of TGF-β could be found. The results are compatible with a decreased production and release, an enhanced clearance or utilization, or tissue accumulation of TGF-β in acuteP. falciparum malaria.

Natural Genetic Transformation of Clinical Isolates of Escherichia coli in Urine and Water

ABSTRACT Transfer of plasmid-borne antibiotic resistance genes in Escherichia coli wild-type strains is possible by transformation under naturally occurring conditions in oligotrophic, aquatic environments containing physiologic concentrations of calcium. In contrast, transformation is suppressed in nitrogen-rich body fluids like urine, a common habitat of uropathogenic strains. Current knowledge indicates that transformation of these E. coli wild-type strains is of no relevance for the acquisition of resistance in this clinically important environment.