Characteristics of salivary cortisol and alpha-amylase as psychobiological study outcomes in palliative care research.

BACKGROUND: Psychosocial interventions are rapidly emerging in palliative care. However, randomized trials often fail to provide evidence for their effectiveness with regard to patient-reported outcomes. Stress biomarkers could complement self-report data, but little is known about their feasibility, acceptance, and interpretability. METHODS: Therefore, we designed a randomized crossover trial in which 42 patients in a palliative care unit participated in both a brief mindfulness intervention (MI) and a resting state control condition (CC) on two consecutive afternoons. On each day, we collected four saliva samples in 20-min intervals using Salivettes© to determine salivary cortisol (sCort) and alpha-amylase (sAA) concentration levels. At all measurement points, self-rated well-being and stress as well as cardiovascular markers were assessed. Baseline measurements further included self-rated quality of life and clinician-rated functional status. RESULTS: 78.6% of the patients provided the maximum number of 8 saliva samples and 62.2% reported no subjective difficulties with the sampling procedures. 66.6% (sCort) and 69.6% (sAA) of all possible samples were finally included in the analysis. Xerostomia and nausea were the main reasons for missing data. Higher sCort levels were associated with higher heart rate and lower quality of life, functional status, and heart rate variability. Corticosteroid and sedative medication as well as time since last meal were identified as potential confounders. Regarding reactivity to the MI, we found an overall decrease in sCort levels over time (b = -.03, p = .01), but this effect did not differ significantly between the study conditions (b = .03, p = .21). sAA levels were higher in men than in women. Trajectories over time did not significantly differ between the two conditions (b = -.02, p = .80) and associations with other stress and health-related constructs were weak. CONCLUSIONS: Findings indicate that sCort might serve as a psychobiological outcome in future palliative care trials. However, future research should refine the exact measurement and conceptualization strategies for sCort in palliative care research. High attrition rates should be expected in patients with xerostomia or nausea. TRIAL REGISTRATION: Registered at the German Clinical Trials Registry (DRKS00013135) at 04/12/2017.

Psychoneuroendocrinological effects of music therapy versus mindfulness in palliative care: results from the 'Song of Life' randomized controlled trial.

PURPOSE: Although research on psychosocial interventions in palliative care provided evidence for their effectiveness regarding patient-reported outcomes, few studies have examined their psychobiological effects yet. Therefore, the purpose of the present work as part of an overarching study was to investigate differential effects of music therapy versus mindfulness on subjective distress and both neuroendocrine and autonomic stress biomarkers. METHODS: A total of 104 patients from two palliative care units were randomly assigned to three sessions of either music therapy or mindfulness. Before and after the second session (completed by 89 patients), participants rated their momentary distress and provided three saliva samples for cortisol and α-amylase analysis. Furthermore, photoplethysmography recordings were continuously assessed to calculate mean heart rate and heart rate variability. Data were analyzed using multilevel modeling of all available data and sensitivity analysis with multiply imputed data. RESULTS: Between 67 and 75% of the maximally available data points were included in the primary analyses of psychobiological outcomes. Results showed a significant time*treatment effect on distress (b = - 0.83, p = .02) indicating a greater reduction in the music therapy group. No interaction effects were found in psychobiological outcomes (all p > .05), but multilevel models revealed a significant reduction in cortisol (b = - 0.06, p = .01) and mean heart rate (b = - 7.89, p = .05) over time following either intervention. CONCLUSION: Findings suggest a beneficial effect music therapy on distress while no differential psychobiological treatment effects were found. Future studies should continue to investigate optimal stress biomarkers for psychosocial palliative care research. TRIAL REGISTRATION: German Clinical Trials Register (DRKS)-DRKS00015308 (date of registration: September 7, 2018).

"Song of Life": Results of a multicenter randomized trial on the effects of biographical music therapy in palliative care.

BACKGROUND: Awareness for the importance of psychological and spiritual needs in patients with terminal diseases has increased in recent years, but randomized trials on the effects of psychosocial interventions are still rare. AIM: To investigate the efficacy of the "Song of Life" music therapy intervention regarding the emotional and psycho-spiritual dimensions of quality of life. DESIGN: Patients were randomly assigned to either "Song of Life" or a relaxation intervention. "Song of Life" is a novel three-session music therapy intervention working with a biographically meaningful song. Primary outcome was the improvement in psychological quality of life. Secondary outcomes included spiritual well-being, ego-integrity, momentary distress, and global quality of life and the explorative assessment of treatment satisfaction (patient and family member version). Intention-to-treat analysis was conducted including adjustment for multiple testing in secondary outcomes. SETTING/PARTICIPANTS: Between December 2018 and August 2020, 104 patients receiving specialized palliative care were recruited from two palliative care wards. RESULTS: No significant differences were found regarding psychological and global quality of life, but "Song of Life" participants reported significantly higher spiritual well-being (p = 0.04) and ego-integrity (p < 0.01), as well as lower distress (p = 0.05) than patients in the control group. Both patients' and family members' treatment satisfaction was higher after "Song of Life" with large between-group effect sizes on items asking for meaningfulness (d = 0.96) and importance (d = 1.00). CONCLUSIONS: Our findings provide evidence that "Song of Life" is an effective and meaningful biographical music therapy intervention to facilitate psycho-spiritual integration in terminally ill patients. TRIAL REGISTRATION: German Clinical Trials Register (DRKS)-DRKS00015308 (date of registration: September 7th 2018).

Stress-reducing effects of a brief mindfulness intervention in palliative care: Results from a randomised, crossover study.

OBJECTIVE: Mindfulness-based interventions are a widely used and highly accepted adjunct treatment in oncology. Due to a paucity of research in advanced cancer and other terminal illnesses, we aimed to evaluate the stress-reducing effects of a brief, standardised mindfulness intervention for use in palliative care. METHODS: This study was a randomised, crossover trial where patients participated in both a single mindfulness intervention and a resting state control condition. The order of the conditions was randomised. Study outcomes encompassed self-report data on stress and well-being and measures of heart rate variability. All outcome data were measured at four times per day. RESULTS: Forty-two patients participated in this study. We found significantly stronger reductions in self-rated stress and mean heart rate as well as an increase in heart rate variability after the mindfulness intervention. Psychophysiological effects were strongest in the immediate pre- to post-intervention comparison, while the effect on subjective stress persisted after 20 to 40 min. No significant differences were found for self-rated well-being. CONCLUSIONS: Despite the rather small magnitude of effects, the brief mindfulness intervention showed to be effective and accepted by patients in very advanced stages of a disease and could be offered by trained healthcare professionals in palliative care.

Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients.

Transdermal fentanyl is widely used to control pain in cancer patients. The high pharmacokinetic variability of fentanyl is assumed to be due to cytochrome P450 3A-mediated (CYP3A) N-dealkylation to norfentanyl in humans. However, recently published clinical studies question the importance of the described metabolic pathway. In this small study in palliative cancer patients under real-life clinical conditions, the influence of CYP3A on fentanyl variability was investigated. In addition to the determination of midazolam plasma concentration to reveal CYP3A activity, plasma concentrations of fentanyl and its metabolite, norfentanyl, were measured in identical blood samples of 20 patients who participated in an ongoing trial and had been on transdermal fentanyl. Fentanyl, norfentanyl, midazolam, and 1'-OH-midazolam were quantified by liquid chromatography/tandem mass spectrometry. Plasma concentrations of fentanyl and norfentanyl exhibited a large variability. Mean estimated total clearance of fentanyl and mean metabolic clearance of midazolam (as a marker of CYP3A activity) were 75.5 and 36.3 L/h. Both clearances showed a weak correlation and hence a minimal influence of CYP3A on fentanyl elimination.

"Song of Life (SOL)" study protocol: a multicenter, randomized trial on the emotional, spiritual, and psychobiological effects of music therapy in palliative care.

BACKGROUND: Although patients in palliative care commonly report high emotional and spiritual needs, effective psychosocial treatments based on high quality studies are rare. First research provides evidence for benefits of psychosocial interventions in advanced cancer care. To specifically address end-of-life care requirements, life review techniques and creative-arts based therapies offer a promising potential. Therefore, the present study protocol presents a randomized controlled trial on the effectiveness of a newly developed music therapy technique that is based on a biographically meaningful song ("Song of Life"; SOL). METHODS: In a design with two parallel arms, 104 patients at two palliative care units will be randomly assigned to three sessions of either SOL (experimental group) or relaxation exercises (control group). Improvements in the psychological domain of quality of life will be the primary endpoint, while secondary outcomes encompass spiritual well-being, ego-integrity, overall quality of life, and distress. Additionally, caregivers will be asked to provide feedback about the treatment. Assessment of biopsychological stress markers and qualitative analysis of perceived strengths and weaknesses will complement data collection. DISCUSSION: Based on the results of a previous pilot study, we dedicated considerable efforts to optimizing the intervention and selecting appropriate outcomes for the present trial. We are confident to have designed a methodologically rigorous study that will contribute to the evidence-base and help to develop the potential of psychosocial interventions in palliative care. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) - DRKS00015308 (date of registration: September 07th 2018).

Patient Experiences With Handling of Analgesic Transdermal Patches and Challenges in Correct Drug Administration: A Pilot Study on Patient Education.

BACKGROUND: Although problems during transdermal patch administration are primarily caused by insufficient knowledge, patient education programs are lacking. We compared patient education by a clinical pharmacist on knowledge on correct patch administration with routine counseling during patient-physician consultation in a pilot study. METHODS: After baseline assessment of knowledge and difficulties with patch administration, patients in the outpatient pain clinic of Heidelberg University Hospital were allocated to intervention (n = 12) or control group (n = 11). In both groups, identical information leaflets on transdermal patch use were dispensed. Intervention patients additionally received verbal counseling on correct patch administration by a clinical pharmacist. After 4 weeks, patients were called for a follow-up assessment on knowledge and perspective on administration difficulties. RESULTS: Patients reported several difficulties with transdermal patch administration, such as local skin reaction, difficulties with opening the packaging, and poor adhesion. Although patient education increased the ratio of correct answers in the intervention group twice as much than in the control group, overall knowledge was comparable between groups after education (P = 0.602). CONCLUSIONS: Patients encountered numerous problems with transdermal patch administration although on long-term use. Patient education can improve knowledge on correct patch administration. However, the pilot study demonstrated the need for further efforts to improve ease of use of transdermal patch, such as patch adhesion.

'Song of Life': music therapy in terminally ill patients with cancer.

OBJECTIVES: Music therapy (MT) holds a promising potential to meet emotional and existential needs in palliative care patients. The aim of the present pilot study was to assess the feasibility, acceptance and potential effectiveness of a novel MT intervention to improve life closure and spiritual well-being of terminally ill patients with cancer receiving palliative care. METHODS: The 'Song of Life' (SOL) intervention was provided on two consecutive sessions containing a biographical interview and a live performance of a song with high biographical relevance to the patient in a lullaby style. Pre-to-post intervention assessments comprised brief self-report measures on life closure, well-being, stress, worry and pain. RESULTS: 13 out of 15 patients were able to complete the protocol as intended. The chosen songs were associated with a close person, an important place or event or with a religious belief. The results showed medium-sized improvements with regard to life closure, well-being, relaxation, worry and pain. CONCLUSION: 'SOL' proved to be a feasible and highly accepted intervention for patients approaching the end of their lives. Further consideration with regard to the procedures and outcomes is necessary before implementation of a randomised trial.

In Vivo CYP3A Activity in Palliative Care Patients: Study Protocol for a Single Arm Prospective Trial.

BACKGROUND: Drug interactions are a common cause for escalation of debilitating symptoms in palliative care patients. CYP3A is the most relevant CYP enzyme in humans involved in metabolism of about half of all available pharmaceuticals. OBJECTIVE: To increase knowledge about the CYP3A enzyme and the impact of drug interactions on its activity to improve dosing in palliative care patients. DESIGN: The prospective clinical trial uses a secure method of analyzing CYP3A activity in humans: Administration of a marker substance followed by the determination of its blood concentrations as well as the concentrations of its metabolite at certain points of time and corresponding metabolic clearance calculations. SETTING: The ongoing trial is carried out at a palliative care unit under real-life clinical conditions. MEASUREMENTS: A four-hour pharmacokinetic profile after oral administration of the marker substance (microdose of midazolam) will be obtained from each enrolled patient. Plasma concentrations of midazolam and its primary metabolite will be quantified by mass spectrometry techniques. CYP3A activity will be calculated as partial metabolic clearance from a limited sampling area under the curve. All other drugs taken by the participating patients will be considered as well as recent blood test results and the patients' diagnoses. CONCLUSIONS: This is the first prospective study dealing with drug metabolism in patients on a palliative care unit. The trial is based on reliable and established methods aiming to provide improved dosing regimens and thus optimize pharmacological therapies in this specialty.

Bleeding Control in Palliative Care Patients With the Help of Tranexamic Acid.

BACKGROUND: Persistent bleeding is a common reason for admitting patients with advanced cancer to a palliative care unit. Several reports show a successful therapeutic use of the antifibrinolytic agent tranexamic acid in palliative care patients having hemorrhages. However, it is not administered routinely in severe bleeding situations in palliative care, and general dosing recommendations are unclear. CASE PRESENTATION: We report on 3 patients who were treated with tranexamic acid due to symptomatic hemorrhage complicating different malignant processes. Case Management and Outcome: A dosing regimen of 1000 mg intravenous tranexamic acid 3 times a day caused an arrest of bleeding in the reported patients within 2 to 3 days. Having controlled the acute bleeding, we continued with an oral administration of 3000 mg per day as maintenance dose. CONCLUSIONS: The described dosing regimen was effective in controlling the symptomatic bleeding of the reported patients. Further studies are needed to get evidence-based information on the optimal dosing regimen of tranexamic acid and to emphasize its significance in palliative medicine.

Chronic Hiccups: An Underestimated Problem.

Persistent singultus, hiccupping that lasts for longer than 48 hours, can have a tremendous impact on a patient's quality of life. Although involved neurologic structures have been identified, the function of hiccups remains unclear-they have been controversially interpreted as a primitive reflex preventing extent swallowing of amniotic fluid in utero, an archaic gill ventilation pattern, or a fetus' preparation for independent breathing. Persistent singultus often presents as a symptom for various diseases, most commonly illnesses of the central nervous system or gastrointestinal tract; they can also be evoked by a variety of pharmacological agents. It is often impossible to define a singular cause. A wide range of treatment attempts, pharmacological and nonpharmacological, have been concerted to this date; however, chlorpromazine remains the only Food and Drug Administration-approved drug in this context. Large-scale studies on efficacy and tolerance of other therapeutic strategies are lacking. Gabapentin, baclofen, and metoclopramide have been reported to accomplish promising results in reports on the therapy of persistent singultus; they may also be effective when given in combination with other drugs, eg, proton pump inhibitors, or as conjoined therapy. As another approach of note, acupuncture treatment was able to abolish hiccups in a number of studies. When managing hiccup patients within the clinical routine, it is of importance to conduct a comprehensive and effective diagnostic workup; a well-functioning interdisciplinary team is needed to address possible causes for the symptom. Persistent singultus is a medical problem not to be underestimated; more research on options for effective treatment would be greatly needed.

Insomnia and Autonomic Function Predict Well-Being in Patients Receiving Palliative Care.

BACKGROUND: The improvement of health-related quality of life (HRQOL) is one of the main treatment goals in end-of-life care. Although definitions and conceptualizations remain heterogeneous, many researchers proposed HRQOL to be considered as subjective patient well-being. However, research on its determinants in palliative care is rare, and little is known about the interplay between psychological and biological variables. OBJECTIVE: The aim of this study was to explain differences in terminally ill patients' acute well-being (AWB) by use of a multimethod approach, examining both self-ratings and physiological predictors. SETTING/SUBJECTS: The study was conducted on a palliative care unit in Heidelberg, Germany. A total of 69 adult patients receiving palliative care were included in the analysis. MEASUREMENTS: Patients filled out the EORTC QLQ-C15-PAL questionnaire and an additional single-item visual analogue scale on AWB. In addition, we recorded a five-minute segment of beat-to-beat fluctuations of heart rate (i.e., heart rate variability, HRV) and calculated three indices of cardiac autonomic function: mean heart rate, the root mean square of successive differences, and the standard deviation of normal-to-normal (SDNN) intervals. Exploratory, multiple regression analyses were used to identify significant predictors among the QLQ subscales and HRV parameters. RESULTS: Insomnia (p < 0.001) and SDNN (p < 0.001) were significantly associated with AWB and together explained 26.3% of the variance. All other predictors including pain, fatigue, and physical functioning failed to reach significance (all p > 0.05). CONCLUSION: Both autonomic dysfunction and sleep disturbances independently explained differences in patient's AWB among terminally ill patients. Their role within the concept of quality of life needs to be further addressed in future studies.

The Impact of Plasma Cholinergic Enzyme Activity and Other Risk Factors for the Development of Delirium in Patients Receiving Palliative Care.

CONTEXT: Delirium is an important complication in palliative care patients. One of the potential risk factors for cognitive disorders is deterioration in cholinergic neurotransmission. Anticholinergic medications are known to be important owing to the association of their metabolites with significant morbidity, which is often the result of cumulative effects of medications (anticholinergic burden). Additionally, cholinergic enzymes are possible candidates reflecting the cholinergic situation in patients. However, the role of cholinesterases (CHE) for delirium in palliative care patients is unknown. OBJECTIVES: Following local Ethics Board approval and written informed consent, we recruited a cohort of patients who had been admitted to the Heidelberg University Palliative Care Unit related to CHE and other factors at risk for delirium. METHODS: Delirium was assessed using the Nursing Delirium Screening Scale once daily in all cancer patients (N = 100) during their stay on the palliative care unit. In a subgroup of 69 probes, blood samples were analyzed for acetyl- and butyrylcholinesterase activity spectrophotometrically. Furthermore, patients' medications were recorded. Logistic regression analysis was used to evaluate potential predictors of delirium. RESULTS: Delirium was identified in 29% of patients. Karnofsky Performance Status Scale score was significantly lower (P = 0.021) and mortality higher (P = 0.018) in patients with delirium. Plasma CHE activity was not associated with delirium. However, a significant effect of anticholinergic medication on plasma CHE activity was detected; so far midazolam (P = 0.01) seems to play an important role in that process. CONCLUSION: Special care might be necessary with anticholinergic medication to minimize risk for delirium in palliative cancer patients.

Trajectories of Terminally Ill Patients' Cardiovascular Response to Receptive Music Therapy in Palliative Care.

CONTEXT: Relaxation interventions are frequently used to promote symptom relief in palliative care settings, but little is known about the underlying mechanisms. OBJECTIVES: The present analysis aimed at examining the psychophysiological pathways of terminally ill patients' cardiovascular response to a live music therapy vs. prerecorded mindfulness exercise. METHODS: Eighty-four patients of a palliative care unit were randomly assigned to either of the two interventions. Multilevel modeling was used to analyze trajectories of physiological change. Vagally mediated heart rate variability (VM-HRV) and blood volume pulse amplitude (BVP-A) served as indices of autonomic nervous system response. Participants' gender, age, baseline scores, self-rated pain, and assignment to treatment were entered to the models as predictors. RESULTS: Both VM-HRV and BVP-A showed significant linear and quadratic trends over time, as well as substantial heterogeneity among individuals' trajectories. Baseline scores, pain, and treatment significantly accounted for random variation in VM-HRV intercepts. BVP-A levels were significantly higher in women than in men. Moreover, assignment to treatment significantly accounted for differences in the linear slopes of peripheral blood flow. CONCLUSION: Higher levels of VM-HRV in the music therapy group highlight the importance of a therapeutic relationship for the effectiveness of relaxation interventions in end-of-life care settings. Music therapy caused significantly stronger reductions of vascular sympathetic tone and, therefore, may be indicated in the treatment of pain and stress-related symptoms in palliative care. Initial self-ratings of pain moderated patients' physiological response and need to be taken into account in clinical practice and future theory building.

Effects of vibroacoustic stimulation in music therapy for palliative care patients: a feasibility study.

BACKGROUND: The present study aimed at examining whether methodological strategies from a previously implemented study design could be transferred to the evaluation of the psychological and physiological effects of a music therapy intervention working with vibroacoustic stimulation in palliative care. METHOD: Nine participants suffering from advanced cancer took part in single-sessions of music therapy, lasting for 30 min. The live music therapy intervention utilized singing chair sounds and vocal improvisation. Visual analogue scales (VAS) were used to assess self-ratings of pain, relaxation, and well-being before and after each session. During the intervention, we continuously recorded heart rate variability (HRV) as a measure of autonomic functioning. Data collection was complemented by a semi-structured interview to explore subjective experiences in more detail. Feasibility was defined as the ability to complete 80 % of the sessions in accordance with the study protocol. RESULTS: In 5 out of 9 sessions (55 %) it was possible to deliver the intervention and obtain all data as intended. VAS assessment was feasible, although graphical and statistical examination revealed only marginal mean changes between pre and post. HRV recordings were subject to artifacts. While HRV parameters differed between individuals, mean changes over time remained relatively constant. Interview data confirmed that the individual perception was very heterogeneous, ranging from "calming" to "overwhelming". CONCLUSION: The criterion of feasibility was not met in this study. Physiological data showed high attrition rates, most likely due to movement artifacts and reduced peripheral blood flow in some participants' extremities. Examination of individual-level trajectories revealed that vibroacoustic stimulation may have an impact on the autonomic response. However, the direction and mechanisms of effects needs to be further explored in future studies. TRIAL REGISTRATION: German Clinical Trials Register - DRKS00006137 (July 4(th), 2014).

Music Therapy in Palliative Care.

BACKGROUND: Music therapy has been used successfully for over 30 years as part of palliative care programs for severely ill patients. There is nonetheless a lack of high-quality studies that would enable an evidence-based evaluation of its psychological and physiological effects. METHODS: In a randomized controlled trial, 84 hospitalized patients in palliative care were assigned to one of two treatment arms--music therapy and control. The music therapy intervention consisted of two sessions of live music-based relaxation exercises; the patients in the control group listened to a verbal relaxation exercise. The primary endpoints were self-ratings of relaxation, well-being, and acute pain, assessed using visual analog scales. Heart rate variability and health-related quality of life were considered as secondary outcomes. The primary data analysis was performed according to the intention-to-treat principle. RESULTS: Analyses of covariance revealed that music therapy was more effective than the control treatment at promoting relaxation (F = 13.7; p <0.001) and well-being (F = 6.41; p = 0.01). This effect was supported by a significantly greater increase in high-frequency oscillations of the heart rate (F = 8.13; p = 0.01). Music therapy did not differ from control treatment with respect to pain reduction (F = 0.4; p = 0.53), but it led to a significantly greater reduction in the fatigue score on the quality-of-life scale (F = 4.74; p = 0.03). CONCLUSION: Music therapy is an effective treatment with a low dropout rate for the promotion of relaxation and well-being in terminally ill persons undergoing palliative care.

Music therapy to promote psychological and physiological relaxation in palliative care patients: protocol of a randomized controlled trial.

BACKGROUND: Music therapy is one of the most frequently used complementary therapies in different palliative care settings. Despite its long tradition and high acceptance by other health-care professionals, evidence on the effectiveness of music therapy interventions for terminally ill patients is rare. Recent reviews and health-care reports consistently point out the need of music therapists to provide an evidence-based rationale for their clinical treatments in this field. Therefore, the present study evaluates the psychological and physiological response of palliative care patients to a standardized music therapy relaxation intervention in a randomized controlled trial. METHODS/DESIGN: A sample of 84 participants from a palliative care unit in Heidelberg is randomized to either two sessions of music therapy or two sessions of a verbal relaxation exercise, each lasting 30 minutes. The music therapy sessions consist of live played monochord music and a vocal improvisation, the control group uses a prerecorded excerpt from the mindfulness-based stress reduction program containing no musical elements. Outcome measures include self-report data on subjective relaxation, well-being, pain intensity, and quality of life, as well as continuous recording of heart rate variability and blood volume pulse as indicators of autonomous nervous system functioning. DISCUSSION: To our knowledge, this study is the first clinical trial in Europe and one of very few randomized controlled trials worldwide to systematically examine the effects of music therapy in palliative care. TRIAL REGISTRATION: German Clinical Trials Register - DRKS00006137.

Predictors of survival in sepsis: what is the best inflammatory marker to measure?

PURPOSE OF REVIEW: Sepsis is relevant due to its high morbidity and mortality. For both sepsis diagnosis and outcome prediction many biomarkers have been described in the literature. Most of these markers are objects of scientific interest rather than being introduced into daily clinical practice. However, due to their unspecific character and their insufficient predictive value for the individual person, research focus is still on new aspects in sepsis-related biomarkers. RECENT FINDINGS: Beyond the widely used acute-phase proteins C-reactive protein (CRP) and procalcitonin (PCT), many new molecules have been studied deriving from different organs or cells affected, due to the systemic nature of sepsis. Cytokines, coagulation factors/characteristics, vasoactive hormones, and several others have been recently proved to be relevant in sepsis syndrome and probably useful for outcome prediction. However, single time point measurements may be less predictive than consideration of the time-dependent course of parameters. Clinical decision just based on a biomarker is still not feasible because of the huge inter-individual differences in the inflammatory response. SUMMARY: Many biomarkers display relevant correlation with the clinical outcome of patients with severe sepsis and septic shock. Consideration of their time courses may be more reliable than absolute levels. Clinical decision should not be based only on biomarkers but organ dysfunctions, for example, should also be taken into account.