The trend to greater use of chemotherapy at the end of life could be explained by patients' and physicians' mutually reinforcing attitudes of "not giving up" and by physicians' broad interpretation of patients' quality of life, in which taking away patients' hope by withholding treatment is considered harmful. To rebalance the ratio of quantity of life to quality of life, input from other health professionals, notably nurses, may be necessary.

We studied the effect of the Liverpool Care Pathway (LCP) on the documentation of care, symptom burden and communication in three health care settings. Between November 2003 and February 2005 (baseline period), the care was provided as usual. Between February 2005 and February 2006 (intervention period), the LCP was used for all patients for whom the dying phase had started. After death of the patient, a nurse and a relative filled in a questionnaire. In the baseline period, 219 nurses and 130 relatives filled in a questionnaire for 220 deceased patients. In the intervention period, 253 nurses and 139 relatives filled in a questionnaire for 255 deceased patients. The LCP was used for 197 of them. In the intervention period, the documentation of care was significantly more comprehensive compared with the baseline period, whereas the average total symptom burden was significantly lower in the intervention period. LCP use contributes to the quality of documentation and symptom control.

No abstract

Palliative sedation is undergoing extensive debate. The aims of this study were to describe the practice of palliative sedation at a specialized acute palliative care unit and to study whether patients who received palliative sedation differed from patients who did not. We performed a systematic retrospective analysis of the medical and nursing records of all 157 cancer patients who died at the acute palliative care unit between 2001 and 2005. Palliative sedation, defined as continuous deep sedation prior to death, was used for 43% of all deceased patients. In 87% of the sedated patients, it was started in the last two days before death. Sedated and nonsedated patients did not differ in survival after admission (eight days vs. seven days, P=0.12). Sedated patients were younger (55 years vs. 59 years, P=0.04) and more often had malignancies of the digestive tract (P<0.01). In both groups, common symptoms at admission were pain (79% vs. 87%, P=0.23), constipation, (40% vs. 48%, P=0.46), and dyspnea (32% vs. 29%, P=0.77). On the day that palliative sedation was started, sedated patients more often suffered from dyspnea and delirium than nonsedated patients at a comparable day before death. The most important indications for palliative sedation were terminal restlessness (60%) and dyspnea (46%). We conclude that at the studied acute palliative care unit, patients who ultimately received palliative sedation did not have symptoms different than nonsedated patients at admission, but on the day at which the sedation was started, they suffered more often from delirium and dyspnea.

Nonlinear disposition of paclitaxel (Taxol) in cancer patients has been described in several studies, but the underlying mechanism is still a matter of speculation. Previously, we have shown in vitro that the paclitaxel formulation vehicle, Cremophor EL (CrEL), alters the blood distribution of paclitaxel as a result of entrapment of the compound in circulating CrEL micelles, thereby reducing the free drug fraction available for cellular partitioning. Based on these findings, we prospectively re-evaluated the linearity of paclitaxel disposition in patients using whole blood and plasma analysis, and sought to define a new pharmacokinetic model to describe the data. Seven patients with solid tumors were treated with paclitaxel infused over 3 h, each at consecutive 3-weekly dose levels of 225, 175 and 135 mg/m2 (CrEL dose level, 18.8, 14.6, and 11.3 ml/m2, respectively). Patient samples were collected up to 24 h after the start of infusion, and analyzed by high-performance liquid chromatography. Paclitaxel peak levels and areas under the curve in whole blood increased linearly with dose, whereas plasma levels showed substantial deviation from linearity. This was shown to be caused by a CrEL concentration-dependent decrease in paclitaxel uptake in blood cells, as reflected by the blood:plasma concentration ratios which altered significantly from 0.83 +/- 0.11 (at 135 mg/m2) to 0.68 +/- 0.07 (at 225 mg/m2). It is concluded that the nonlinear disposition of paclitaxel is related to paclitaxel dose-related levels of the formulation vehicle CrEL, leading to a disproportionate drug accumulation in the plasma fraction. The pharmacokinetic model developed accurately described the data, and will help guide future development and refinement of clinical protocols, especially in defining the exposure measure best linked to paclitaxel effects and toxicities.

Death rattle is a rather common symptom in dying patients, but it is doubtful if patients suffer from this symptom. Current literature does not support the standard use of antimuscarinic drugs in the treatment of death rattle.

The non-ionic surfactants Cremophor EL (CrEL) and Tween 80, both used as formulation vehicles of many (anticancer) agents including paclitaxel and docetaxel, are not physiological inert compounds. We describe their biological properties, especially the toxic side effects, and their pharmacological properties, such as modulation of P-glycoprotein activity. In detail, we discuss their influence on the disposition of the solubilized drugs, with focus on CrEL and paclitaxel, and of concomitantly administered drugs. The ability of the surfactants to form micelles in aqueous solution as well as biological fluids (e.g. plasma) appears to be of great importance with respect to the pharmacokinetic behavior of the formulated drugs. Due to drug entrapment in the micelles, plasma concentrations and clearance of free drug change significant leading to alteration in pharmacodynamic characteristics. We conclude with some perspectives related to further investigation and development of alternative methods of administration.

Relatives emphasized their relation with the patient and their involvement in care of the patient dying in the hospital. An approach of HCPs to care based on the concept of individual autonomy seems inadequate. The role of relatives might be better addressed by the concept of relational autonomy, which provides HCPs with opportunities to create a relationship with relatives in care that optimally addresses the needs of patients.