Central venous access related adverse events after trabectedin infusions in soft tissue sarcoma patients; experience and management in a nationwide multi-center study.

Background Trabectedin has shown efficacy against soft tissue sarcomas (STS) and has manageable toxicity. Trabectedin is administered through central venous access devices (VAD), such as subcutaneous ports with tunneled catheters, Hickman catheters and PICC lines. Venous access related adverse events are common, but have not yet been reported in detail.Methods A retrospective analysis of patient files of STS patients receiving trabectedin monotherapy between 1999 and 2014 was performed in all five STS referral centers in the Netherlands. This survey focused on adverse events related to the VAD and the actions taken in response to these events.Results In the 127 patients included in this analysis, 102 venous access ports (VAP), 15 Hickman catheters and 10 PICC lines were used as primary means of central venous access. The most frequently reported adverse events at the VAD site were erythema (30.7%), pain (28.3%), inflammation (11.8%) and thrombosis (11.0%). Actions taken towards these adverse events include oral antibiotics (17.3%), VAD replacement (15.0%) or a wait-and-see policy (13.4%). In total, 45 patients (35.4%) with a subcutaneous port developed a varying degree of inflammation along the trajectory of the tunneled catheter. In all but three patients, this was a sterile inflammation, which was considered a unique phenomenon for trabectedin. Microscopic leakage of trabectedin along the venous access device and catheter was considered the most plausible cause for this adverse event. Placing the catheter deeper under the skin resolved the issue almost completely.Conclusion Trabectedin infusion commonly leads to central venous access related adverse events. Sterile inflammation along the catheter trajectory is one of the most common adverse events and can be prevented by placing the catheter deeper under the skin

Heart rate variability as a predictor of mortality in patients with AA and AL amyloidosis

Aims Patients with AA and AL amyloidosis have a limited life-expectancy. The aim of this study was to investigate whether heart rate variability can predict mortality in these patients. Methods and Results Twenty-two recently diagnosed patients with AA and 23 patients with AL amyloidosis were included, Fifteen patients (5 AA, 10 AL) died within 1 year. Twenty-four hour Holter recording was performed to quantify the mean or all normal to normal RR-intervals (mean NN) and the standard deviation of all normal to normal RR-intervals (SDNN). The SDNN predicted 1-year mortality in the total group of patients with amyloidosis. The median SDNN was 73 ms. In patients with an SDNN less than or equal to 73 ms, the risk of dying within 1 year was found to have increased 3.5-fold (P=0.0036; 95% CI 1.1 11.0). An SDNN less than or equal to 50 ms, a predictor of mortality in other patient groups, increased the risk of dying within 1 year 22-fold (P=0.0001; 95% CI 5.4-90.4). In contrast to patients with AA amyloidosis, in the subgroup analysis of patients with AL amyloidosis the SDNN remained a predictive parameter (SDNN less than or equal to 50ms: risk ratio 11.5, 95% CI 2.4-56.2, P=0.0025). Conclusion The SDNN is a strong predictor of short-term mortality in patients with AL amyloidosis. (C) 2002 The European Society of Cardiology

The assessment of autonomic function in patients with systemic amyloidosis: methodological considerations

Autonomic neuropathy is a well-known and prognostically important feature of systemic amyloidosis. In other conditions, autonomic function is commonly assessed by cardiovascular reflex rests, described by Ewing, but the feasibility of these tests has not been investigated in patients with systemic amyloidosis. We studied autonomic function in amyloidotic patients using cardiovascular tests and assessed their feasibility. Patients with AA, AL and ATTR amyloidosis participated. In all patients, cardiovascular reflex testing (mental arithmetic stress test and head-lip tilting, besides the Ewing-tests) was performed. Of the 46 patients included, only 28 patients could perform all 4 Ewing-tests. In particular, patients with AA amyloidosis secondary to rheumatoid arthritis could not perform standing up and the isometric handgrip test, However, when the mental stress test replaced the handgrip test and head-up tilting replaced standing up, in 45 of the 46 patients, autonomic function could be assessed with cardiovascular reflex tests. Half of the patients with AA amyloidosis had signs of autonomic neuropathy-which was more than expected. We propose to replace the isometric handgrip test with the mental arithmetic stress test and standing up with head-up tilting if a patient is not able to perform these tests

Re-evaluation of the cold face test in humans

The cold face test has been found to be a simple clinical test to elicit the diving reflex, which assesses function of the sympathetic and parasympathetic nerve systems at the same time. However, there is no consensus about how the test should be performed without confounding the results by eliciting other reflexes, such as the oculocardiac reflex. The object of this study was to compare and standardize methods for per forming the cold face test. Reproducibility of results was assessed. Groups of 6 to 11 subjects participated in each protocol. To act as a cold stimulus a bag filled with iced-water and having a wet surface was used. The effects of allowing breathing to continue, of different masses of the bag, and of avoiding ocular pressure by wearing diving goggles were investigated. Blood pressure and heart rate were measured beat to beat using an automatic blood pressure measuring device. The cold stimulus used in this study was too small to elicit the oculocardiac reflex: wearing diving goggles and different masses of the bag had no influence on the response. The prevention of breathing, however, tended to enhance the fall ill heart rate during the cold stress. Reproducibility was highest when the subjects were habituated to the intensity of the stimulus. We recommend practising the test method in advance and performing it in a setting where the subject is unable to breathe