Cryopreservation of platelets at the end of their conventional shelf life leads to severely impaired in vitro function.

Storage time for platelet concentrates (PCs) is limited to five days due to 'aging' of the platelets and an increasing risk of bacterial proliferation. Storage time can be prolonged by cryopreservation. We investigated in vitro function of six consecutive PCs at the end of their conventional shelf life followed by cryopreservation for 24 hours. Spontaneous, adenosine diphosphate (ADP)-induced and collagen-induced activation before and after cryopreservation were determined by flow cytometry. Additionally, ADP- and collagen-induced aggregation was measured. After cryopreservation two-thirds of the platelets were spontaneously activated, twice as many as before the procedure (p < 0.001). ADP-induced activation was significantly reduced (p = 0.014). Collagen-induced activation was unchanged. Aggregation stimulated by ADP and collagen was significantly reduced (p = 0.005 and p = 0.009, respectively). Our results show severely impaired in vitro function of platelets after storage at 22 degrees C for five days followed by cryopreservation. Cryopreservation of PCs after a storage time of five days cannot be recommended.

The functional integrity of platelets in volume-reduced platelet concentrates.

Premature and low-birth-weight infants usually require small-volume platelet transfusions to treat thrombocytopenia. Also, infants undergoing open-heart surgery with extracorporeal circulation and with compromised cardiac function are at risk for excessive intravascular volume. The small-volume platelet substitution can be achieved by dispensing an aliquot from the unit of a standard single-donor platelet concentrate (PC). Alternatively, there is an indication for volume reduction of PCs to maximize the number of platelets transfused in the smallest possible volume. We determined the spontaneous and induced activation of platelets before and after volume reduction in 20 consecutive single-donor-apheresis PCs. After a mean storage time of 2 days, the PCs were plasma-depleted by centrifugation. Spontaneous, adenosine diphosphate (ADP)-induced, and collagen-induced activation were determined by flow cytometry. Furthermore, ADP- and collagen-induced aggregation were measured. A total of 33.8% of platelets in standard PCs were activated spontaneously. Volume reduction of PCs led to a mild but significant increase of spontaneous activation of platelets (43.2%). Additionally, volume reduction resulted in an impaired ADP-induced aggregability of platelets, whereas collagen induction was unaffected. Transfusion of volume-reduced PCs is an effective alternative to use of standard PCs in patients at frequent risk for excessive intravascular volume, because equal volumes increase the platelet count twice as effectively.

Pre-operative intercostal nerve blockade for minimally invasive coronary bypass surgery: a standardised anaesthetic regimen for rapid emergence and early extubation.

BACKGROUND: Minimally invasive direct coronary artery bypass grafting (MIDCAB) has become a popular adjunct to cardiac bypass surgery in selected patients. Although MIDCAB without cardiopulmonary bypass is considered to be a relatively noninvasive procedure, the trauma to the muscle tissue caused by the anterolateral thoracotomy often leads to more pain than that of patients undergoing routine sternotomy. The purpose of our study was to evaluate the pre-operative application of an intercostal nerve blockade, combined with general anaesthesia for peri- and postoperative pain control, and its efficacy for early extubation. METHODS AND RESULTS: Nine consecutive patients undergoing MIDCAB surgery were evaluated. Pre-operative ipsilateral intercostal nerve blockade was employed in all patients. After induction, isofluran (0.4-0.8%) and nitrous oxide in combination with the pre-operative nerve blockade provided sufficient anaesthesia throughout the procedure (mean operative time: 147 min). Only 2/9 patients required additional small doses of narcotics. All patients could be safely extubated within 15 minutes of skin suture. Postoperative discomfort and pain were minimal. CONCLUSION: From our initial experience with preoperative intercostal nerve blockade for the MIDCAB procedure, we concluded that it provides profound somatic analgesia as an effective adjunct to general anaesthesia with reduced doses of narcotics and sedatives. MIDCAB impresses with its ease of technical performance, its reliability and safety. The minimised chest-wall pain improves patients' chances of early tracheal extubation. In accordance with the minimally invasive surgical approach, it provides a contribution towards 'minimally invasive anaesthesia'. The surgeons' and the patients' acceptance is excellent. Because the results of this study are based on observation and verbalisation of the investigators' impressions, and no objective measurements were made which would have allowed a comparison between the MIDCAB technique and the golden standard of general anaesthesia with opioid analgesia, a further study should be conducted to prove our theory.

Platelet activity in washed platelet concentrates.

Life-threatening anaphylaxis or febrile nonhemolytic transfusion reactions after transfusion of platelet concentrates (PCs) is a serious clinical problem caused by the sensitizing of recipients to plasma components, such as immunoglobulin A, or by cytokines. There is a possible indication for washing of PCs in these thrombocytopenic patients. However, only platelets that show activation after physiological stimulation are useful. We determined the spontaneous and induced activation of platelets before and after washing. We investigated 11 consecutive single-donor-apheresis PCs. After production and leukocyte-depletion the PCs were washed in 15%, acid-citrate-dextrose-solution. The spontaneous and the adenosine diphosphate (ADP)-induced, as well as collagen-induced activation, were determined by flow cytometry. Additionally, ADP- and collagen-induced aggregation were measured. Unwashed platelets (16.1%) were activated spontaneously. The washing of PCs led to a threefold increase of spontaneous activation of platelets (47.4%). Because of increased spontaneous activation after washing we could demonstrate cytometrically a loss of induced activation of washed platelets. Furthermore, washing resulted in an impaired ADP-induced aggregability of platelets. These results have led us to reduce the frequency of washing of PCs in our institution, where the only current indication for washing of PCs is in patients with a history of severe nonhemolytic transfusion reactions.

Bedside exclusion of clinically significant recirculation volume during venovenous ECMO using conventional blood gas analyses.

STUDY OBJECTIVE: To investigate prospectively whether blood gas samples drawn from extracorporeal membrane oxygenation (ECMO) cannulae help to exclude at least clinically significant recirculation volumes in patients with acute respiratory failure. DESIGN: Feasibility study. SETTING: Intensive care unit at a university-affiliated hospital. PATIENTS: Ten consecutive adult patients suffering from severe respiratory failure and undergoing ECMO. INTERVENTIONS: The drawing (venous) ECMO cannula was placed into the inferior vena cava via a femoral vein, and the oxygenated blood was returned via the right subclavian vein by supraclavicular access directly into the right atrium. Blood gas samples were obtained from both cannulae. MEASUREMENTS AND MAIN RESULTS: The median arterial oxygen tension (PaO(2)) obtained from the arterial cannula was 537 mmHg (range, 366 to 625 mmHg), the median mixed venous oxygen tension (PvO(2)) drawn from the venous cannula was 42 mmHg (range, 25 to 54 mmHg), which was less than 10% of that observed in the arterial cannula, and also within the physiologic range of PvO(2). The ECMO flow necessary to maintain patients' oxygen saturation above 90% (4.1 L/min; range, 1.95 to 5.8 L/min) was significantly lower than the patients' cardiac output (CO; 6.2 L/min; range, 4.1 to 7.9 L/min; p < 0.001). CONSLUSIONS; We recommend obtaining blood gas samples-immediately after initiation of ECMO-from both cannulae. A PvO(2) within physiologic range and below 10% of PaO(2) rules out any clinically relevant recirculation volume.

Survival improvement in patients with glioblastoma multiforme during the last 20 years in a single tertiary-care center.

METHODOLOGY: The survival of 357 consecutive patients with newly diagnosed glioblastoma multiforme (GBM) in three treatment groups reflecting different time-periods of diagnosis (A: 1982-1984; B: 1994/1995; C: 1996-1998) was analysed to assess the impact and the potential improvement of changing treatment strategies in our tertiary-care center. PATIENTS AND METHODS: Group A (n = 100) included all consecutive patients diagnosed from 1982 to 1984 and served as the historical control. Group B (n = 93) included all consecutive patients diagnosed in 1994/1995 and group C (n = 164) those diagnosed from 1996 to 1998. Survival in the three treatment groups (A vs. B vs. C) was analysed according to treatment given after neurosurgical intervention (i.e. no specific therapy versus radiotherapy versus combined radio-/chemotherapy), and according to first-line chemotherapy, age (< 40, 40-60, > 60), sex, and tumor location (hemispheric versus bilateral or multifocal tumors, and tumors involving eloquent brain areas). Survival was analysed using Kaplan-Meier's non-parametric method. A p-value < 0.05 was considered statistically significant. RESULTS: Patients in groups A and B received radio- and/or chemotherapy to a varying extent (radiotherapy: group A: 22%, group B: 62%; chemotherapy: group A: 6%, group B: 33%). Chemotherapy was administered after termination of radiotherapy in both groups. In group C, 96% of patients received combined radio-/chemotherapy which was administered concomitantly and started within three weeks after surgery. Median survival was 5.2 months in group A, 5.1 months in group B and 14.5 months in C (p < 0.0001). Nine patients in group A (9%), 9 in group B (10%) and 40 in group C (25%) survived more than 18 months (p < 0.05). CONCLUSIONS: Survival improvement in group C might be attributable to the early start of combined radio-/chemotherapy. Therapy was administered on a complete outpatient basis, enabled by a dedicated interdisciplinary neuro-oncologic team caring for group C. Toxicity was mild and patients' acceptance excellent.

Unexpected out-of-hospital deaths in persons aged 85 years or older: an autopsy study of 1886 patients.

PURPOSE: The aim of this study was to determine the causes of death in the very elderly. METHODS: We reviewed 24,081 consecutive autopsies performed over 10 years (1989 to 1998) at the Institute of Forensic Medicine, Vienna, Austria. We focused on autopsies of people aged 85 years or older who died unexpectedly out of hospital. RESULTS: The mean age of the 1886 patients (561 men and 1325 women) at the time of death was 88 +/- 3 years (range, 85 to 108 years). Thirty-one percent (n = 588) of those who died were described as having been previously healthy. Cardiovascular disease was the most common cause of death (n = 1465 [77%]). Thirteen percent (n = 246) died of respiratory illness, 5% (n = 94) of gastrointestinal disorders, and 3% (n = 53) of diseases of the central nervous system. Genitourinary and metabolic diseases were uncommon. CONCLUSION: Although this out-of-hospital sample is not representative of the entire elderly population, postmortem examinations emphasize the importance of cardiovascular diseases in causing unexpected deaths in older persons.

Feasibility and toxicity of CCNU therapy in elderly patients with glioblastoma multiforme.

In our institution, 103 glioblastoma multiforme (GBM) patients aged from 55 to 83 years were treated since November 1994 as follows. All patients underwent surgical intervention (gross total resection, n = 35; subtotal resection, n = 38; stereotactic biopsy, n = 30). Subsequently all patients were offered radiotherapy and chemotherapy with CCNU. Results were as follows: 101 patients started radiotherapy, 93 patients completed it (96% of the patients aged < 65 years and 85% of the patients > or =65 years). All patients received at least 1 cycle of chemotherapy (median 3 cycles). Chemotherapy-associated toxicity was generally mild, more pronounced in females and did not increase with age. Median time to progression was 10.5+/-3.2 months for the patients < 65 years and 5.1+/-1 months for patients > or =65 years. median overall survival was 17.5+/-3.8 months in patients < 65 years and 8.6+/-1 months in patients > or =65 years (p < 0.0001). In multivariate analysis, age and female sex remained independent prognostic factors. Our data indicate that a treatment concept including concomitant radio- and chemotherapy is feasible even in elderly patients with GBM.

Carotid resection and reconstruction for locally advanced head and neck tumors.

Head and neck surgeons hesitate to resect the carotid artery because of the postoperative risk of neurologic sequelae. However, there is no curative therapeutic option for head and neck neoplasms involving the carotid artery, with the exception of complete tumor removal. To evaluate the benefits and risks of carotid revascularization techniques in locally advanced head and neck tumors we performed a retrospective analysis in an institutional, tertiary care medical center. Seven patients (5 males, 2 females) with a median age of 58 years underwent en bloc removal of locally advanced head and neck tumors, including carotid resection and revascularization, in the University of Vienna General Hospital, over a 15-year period. In six patients carotid reconstruction was accomplished by bypass grafting (five autologous grafts, one synthetic graft) and in one patient angiopatchplasty was used. There were no perioperative neurologic complications or deaths. Survival was > 12 months in 5/7 patients; the other 2 patients died within 6 months due to untractable progression of cancer. We conclude that carotid revascularization techniques offer the possibility of better local control for advanced head and neck tumors without additional risks of neuromorbidity or mortality.

Alterations in intestinal permeability following the intensified polydrug-chemotherapy IFADIC (ifosfamide, Adriamycin, dacarbazine).

PURPOSE: The aim of this study was to investigate the severity and time-course of alterations in gastroduodenal and intestinal permeability in relation to nausea/emesis following administration of the highly emetogenic polydrug regimen IFADIC (ifosfamide, Adriamycin, dacarbazine) using a differential lactulose/mannitol absorption (SLM) test. We also assessed the ease of administration and patients' tolerance of the SLM test. METHODS: The SLM test was performed in seven patients with soft tissue sarcomas on days 1, 3 and 14 of cycle I and cycle III of chemotherapy; seven healthy volunteers served as controls. The degree of correlation between the clinical grade of nausea/emesis according to WHO criteria and gastroduodenal permeability, expressed in terms of urinary sucrose excretion, and intestinal permeability, expressed in terms of the permeability index (urinary lactulose to mannitol permeability ratio), was also assessed. RESULTS: The permeability index values were significantly different (P < or =0.01) on days 1, 3 and 14 during both cycles of chemotherapy. The median permeability index on day 3 was higher (P < =0.01) in patients with nausea/emesis than in those without symptoms. Additionally, the permeability index when nausea was present (day 3) was higher (P < or =0.01) than when nausea/emesis was absent (days 1 and 14). In 59% of patients the increased permeability index on day 3 was accompanied by nausea/emesis of WHO grade 3. Gastroduodenal permeability did not alter consistently following chemotherapy. CONCLUSIONS: Our study confirms an acute, transient increase in intestinal permeability following the polydrug regimen IFADIC, accompanied by nausea/emesis of WHO grade 3 in the majority of patients. Normal intestinal permeability was achieved on day 14 in all patients, thus allowing intensified 2-weekly treatment administration. The SLM test may be recommended as a feasible test for the objective assessment of alterations in intestinal permeability following chemotherapy administration.

Unilateral chronic thromboembolic pulmonary disease associated with combined inherited thrombophilia.

Chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be an extreme variant of pulmonary thromboembolism. The underlying mechanisms for the failure of thrombus resolution are still unclear. In looking for inherited thrombophilia, an association with a lupus anticoagulant has been described repeatedly, and single cases of anticoagulant deficiencies (ie, antithrombin [AT], protein C, and protein S) have been reported. We describe a young patient with type I AT deficiency, the heterozygous prothrombin G20210A mutation, and unilateral chronic thromboembolic pulmonary disease presenting after a single thrombotic event. Pulmonary vascular patency was restored successfully by surgical pulmonary thromboendarterectomy. This case is unique because unilateral CTEPH is extremely uncommon, and it illustrates the severe clinical sequelae of the cosegregation of inherited thrombophilic defects.

Emergency percutaneous retrieval of a silicone port catheter fragment in pinch-off syndrome by means of an Amplatz gooseneck snare.

Rupture of a silicone Port-a-Cath catheter may occur, especially with costoclavicular pinch-off syndrome (POS), which is a typical consequence of fatigue when the catheter is introduced in the subclavian vein too medially. This case report describes the percutaneous retrieval of a fractured silicone port catheter fragment, which had migrated into the internal jugular vein. Extraction was complicated by the presence of an internal jugular vein stenosis and the fact that the catheter fragment was looped upon itself. Several retrieval devices failed before an Amplatz gooseneck snare finally allowed retrieval of the fragment. We recommend this device for extraction of silicone port catheter fragments. Rerupture of the port catheter occurred 7 months after surgical reinsertion at the same infraclavicular site, as a consequence of constant compression by POS. Alternative approaches should be used after catheter failure due to POS.