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BACKGROUND: As frontline caregivers, nurses often find themselves at the crossroads of complex ethical decisions that can significantly impact patient outcomes and their own well-being. Identifying the areas of experienced moral dilemmas in the workplace and gaining insight into the prevalence of moral distress can lead to a healthier workplace environment. OBJECTIVE: This study aims to examine the frequency, intensity and level of moral distress among nurses who work in a hospital, and to identify the variables associated with the level of moral distress. DESIGN: Cross-sectional study. SETTING: One university hospital and six general hospitals. PARTICIPANTS: 654 of the 1095 nurses working on inpatient units filled out the questionnaire (response rate 60â¯%). METHODS: The intensity and frequency of moral distress was assessed using the Moral Distress Scale-Revised (MDS-R). We also asked two additional questions about considering leaving their job, and if they could describe a distressing case and how moral distress was discussed. Multivariable regression analysis was conducted to identify the variables associated with the level of moral distress. RESULTS: The overall mean MDS-R score of the 654 included nurses was low at 36.4 (SD 26). Nurses reported to have frequent dilemmas regarding organizational aspects and aspects of end-of-life care. The multivariable analyses showed that higher levels of moral distress were experienced by registered nurses, nurses working on a medical ward, and nurses who had ever left or considered leaving their job, or considering leaving their job at the moment. CONCLUSIONS: Although nurses in our study experiences low levels of moral distress, they do experience moral dilemmas related to organizational topics and end of life care. We all need to pay attention to these dilemmas and how to discuss them in order to achieve a resilient nursing profession at a time of major nursing shortages. TWEETABLE ABSTRACT: Caring for increasingly complex patients in a dynamic healthcare system is likely to continue to produce morally challenging scenarios.
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BACKGROUND: Healthcare in Germany is not always needs-based and has considerable potential for optimization. Internal medicine (IM) plays a special role in the German healthcare system due to its long tradition. Against this background, a look at the optimization potential to achieve better quality and higher efficiency care seems particularly relevant. OBJECTIVE: Based on an international comparison and taking ambulatory care-sensitive conditions (ACSC) into account, this study aims to identify the steering potential in IM and to discuss it in the context of current reform plans. MATERIAL AND METHODS: The descriptive analysis was carried out as part of a report commissioned by the German Society of Internal Medicine and is based on data from the Federal Statistical Office and Eurostat as well as the ACSC catalogue developed for Germany. RESULTS: The top 10 reasons for inpatient treatment in IM include 7 ACSCs. These diagnoses account for almost one quarter of cases and treatment days and mostly relate to cardiology. The international comparison including numerous other indications shows that other countries have both significantly fewer cases and shorter lengths of stay for most indications. CONCLUSION: The results show that IM in Germany has considerable potential for optimization of inpatient care. In light of the regional variation in service providers and utilization as well as the potential for avoiding inpatient treatment, the current reform plans represent an opportunity for the reorientation of IM. Not least because of its high relevance, also in terms of numbers, it is therefore right and important that it is given such strong consideration within the reform plans.
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BACKGROUND: In the recent years, digital intensive care unit (ICU) diaries have emerged as more advantageous than paper diaries. Despite the advantages of digital diaries, the successful implementation and maintenance of this digital intervention present significant challenges in clinical practice. Therefore, understanding the facilitators and barriers among stakeholders influencing this process becomes imperative for devising a tailored strategy to integrate digital diaries effectively within ICU settings. AIM/OBJECTIVE: The aim of this study was to explore facilitators and barriers for implementation of a digital ICU diary from the perspectives of ICU professionals, ICU survivors, and their relatives. METHODS: A qualitative design was used, incorporating focus-group interviews with professionals from four Dutch ICUs, along with individual interviews with ICU survivors and relatives. The study spanned from October 2022 to April 2023. Data analysis utilised a mixed inductive-deductive approach, particularly through directed content analysis. The Consolidated Framework for Implementation Research 2.0 guided both data collection and analysis processes. FINDINGS: We conducted five focus-group interviews among ICU professionals (n = 32) and 10 individual or dual interviews involving five ICU survivors and nine relatives. Key facilitators for implementing a digital diary according to ICU professionals encompassed a user-friendly interface accessible independent of time and place, with a seamless login process requiring minimal steps, comprehensive training covering all aspects of its use, and feedback from the experiences of both patients and relatives. Barriers for ICU professionals included many steps required to access the digital diary, as well as resistance to (co)writing diary entries. In contrast, professionals' involvement in writing diary entries was highly appreciated among ICU survivors and relatives. An ambiguous factor arose regarding sharing the digital diary with others; both ICU survivors and relatives found it valuable, yet it also raised privacy concerns. CONCLUSIONS: This study offers insights into the most important factors influencing the implementation of a digital ICU diary. Strikingly, some factors serve as both barriers and facilitators. When developing the implementation strategy, the identified facilitators can be used to overcome the barriers faced by ICU professionals, ICU survivors, and their relatives in adopting a digital diary.
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Diaries as Topic , Focus Groups , Intensive Care Units , Qualitative Research , Humans , Male , Female , Netherlands , Adult , Middle Aged , Interviews as Topic , Survivors/psychologyABSTRACT
INTRODUCTION: In Germany, many cancer patients are treated outside of cancer centres certified by the German Cancer Society (DKG) resulting in underuse of these facilities and inferior oncological treatment. One way to address this issue would be to restructure the healthcare landscape by following the Danish approach that limits cancer treatment to specialized hospitals. Such an approach would have an impact on the travelling times to treatment centers. The present study determines the impact on patient travel times using the example of colorectal cancer. METHODS: For the present analysis, data from structured quality reports (sQB) and from patients insured with the AOK who underwent resection of the colon or rectum during 2018 were used. In addition, data from the DKG regarding an existing certification of a colorectal cance centre were used. Travel time was defined as the time patients spent in an average car with average traffic from the midpoint of the ZIP code of their residence to the coordinates of the hospital. The coordinates of the hospitals and the midpoints of the ZIP codes were obtained by querying the Google API. Travel times were calculated with a local Open Routing Machine server. The statistical programs R and Stata were used for analyses and cartographic representations. RESULTS: In 2018, nearly half of all patients with colon cancer were treated at the hospital nearest to their place of residence, of whom approximately 40% were treated at a certified colorectal cancer centre. Overall, only about 47% of all treatments took place at a certified colorectal cancer centre. Travel time to the chosen treatment site averaged 20 minutes. It was minimally shorter (18 minutes) if no certified centre was chosen and minimally longer (21 minutes) for those whose treatment took place in a certified colorectal cancer centre. Modeling of redistributions of all patients to certified centres resulted on an average travel time of 29 minutes. CONCLUSION: Even if treatment were limited to specialized hospitals, treatment close to home would still be guaranteed. Regardless of certification, parallel structures can be identified, especially in metropolitan areas, which indicate a potential for restructuring.
Subject(s)
Cancer Care Facilities , Colorectal Neoplasms , Humans , Germany/epidemiology , Delivery of Health Care , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/surgery , Certification , TravelABSTRACT
The Danish hospital landscape has been continuously restructured since the early 2000s. A structural reform reorganized the public sector, and a hospital reform restructured the hospital landscape, closing hospitals and concentrating specialized treatment in so-called super-hospitals. Reforms can generate considerable debate, including in the media, especially regarding sensitive topics like healthcare. The present study explores the media's coverage of the hospital reform, the antecedent structural reform, and three events related to differences in treatment outcomes, whose importance was pointed out in expert interviews. The coverage is analyzed regarding quantity and main theme (agenda-setting): tone and whether the focus was on single events (episodic framing) or broader context (thematic framing). We used a systematic keyword search to identify relevant news stories and analyzed the headlines and lead paragraphs of 1192 news stories. The three events generated a large amount of coverage, but some events varied in terms of context and tone of coverage. Further, the media covered hospital closures in connection with the two reforms differently in context and tone, although the first difference is not statistically different. Overall, the coverage of the events might have helped raise the public's awareness of challenges in the healthcare system, which could have contributed to opening a window of opportunity for a hospital reform.
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Health Facilities , Hospitals , Humans , DenmarkABSTRACT
PURPOSE: Supporting the provision of intensive care medicine through telehealth potentially improves process quality. This may improve patient recovery and long-term outcomes. We investigated the effectiveness of a multifaceted telemedical programme on the adherence to German quality indicators (QIs) in a regional network of intensive care units (ICUs) in Germany. METHODS: We conducted an investigator-initiated, large-scale, open-label, stepped-wedge cluster randomised controlled trial enrolling adult ICU patients with an expected ICU stay of ≥ 24 h. Twelve ICU clusters in Berlin and Brandenburg were randomly assigned to three sequence groups to transition from control (standard care) to the intervention condition (telemedicine). The quality improvement intervention consisted of daily telemedical rounds guided by eight German acute ICU care QIs and expert consultations. Co-primary effectiveness outcomes were patient-specific daily adherence (fulfilled yes/no) to QIs, assessed by a central end point adjudication committee. Analyses used mixed-effects logistic modelling adjusted for time. This study is completed and registered with ClinicalTrials.gov (NCT03671447). RESULTS: Between September 4, 2018, and March 31, 2020, 1463 patients (414 treated on control, 1049 on intervention condition) were enrolled at ten clusters, resulting in 14,783 evaluated days. Two randomised clusters recruited no patients (one withdrew informed consent; one dropped out). The intervention, as implemented, significantly increased QI performance for "sedation, analgesia and delirium" (adjusted odds ratio (99.375% confidence interval [CI]) 5.328, 3.395-8.358), "ventilation" (OR 2.248, 1.198-4.217), "weaning from ventilation" (OR 9.049, 2.707-30.247), "infection management" (OR 4.397, 1.482-13.037), "enteral nutrition" (OR 1.579, 1.032-2.416), "patient and family communication" (OR 6.787, 3.976-11.589), and "early mobilisation" (OR 3.161, 2.160-4.624). No evidence for a difference in adherence to "daily multi-professional and interdisciplinary clinical visits" between both conditions was found (OR 1.606, 0.780-3.309). Temporal trends related and unrelated to the intervention were detected. 149 patients died during their index ICU stay (45 treated on control, 104 on intervention condition). CONCLUSION: A telemedical quality improvement program increased adherence to seven evidence-based German performance indicators in acute ICU care. These results need further confirmation in a broader setting of regional, non-academic community hospitals and other healthcare systems.
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Critical Care , Telemedicine , Adult , Humans , Critical Care/methods , Intensive Care Units , Lung , RespirationABSTRACT
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has developed into an unprecedented global challenge. Differences between countries in testing strategies, hospitalization protocols as well as ensuring and managing ICU capacities can illustrate initial responses to a major health system shock, and steer future preparedness activities. METHODS: Publicly available daily data for 18 European countries were retrieved manually from official sources and documented in an Excel table (March-July 2020). The ratio of tests to cases, the share of hospitalizations out of all cases and the share of ICU admissions out of all hospitalizations were computed using 7-day rolling averages per 100 000 population. Information on country policies was collected from the COVID-19 Health System Response Monitor of the European Observatory on Health Systems and Policies. Information on health care capacities, expenditure and utilization was extracted from the Eurostat health database. RESULTS: There was substantial variation across countries for all studied variables. In all countries, the ratio of tests to cases increased over time, albeit to varying degrees, while the shares of hospitalizations and ICU admissions stabilized, reflecting the evolution of testing strategies and the adaptation of COVID-19 health care delivery pathways, respectively. Health care patterns for COVID-19 at the outset of the pandemic did not necessarily follow the usual health service delivery pattern of each health system. CONCLUSIONS: This study enables a general understanding of how the early evolution of the pandemic influenced and was influenced by country responses and clearly demonstrates the immense potential for cross-country learning.
Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , Delivery of Health Care , Humans , Policy , SARS-CoV-2ABSTRACT
BACKGROUND: The exponential increase in SARS-CoV-2 infections during the first wave of the pandemic created an extraordinary overload and demand on hospitals, especially intensive care units (ICUs), across Europe. European countries have implemented different measures to address the surge ICU capacity, but little is known about the extent. The aim of this paper is to compare the rates of hospitalised COVID-19 patients in acute and ICU care and the levels of national surge capacity for intensive care beds across 16 European countries and Lombardy region during the first wave of the pandemic (28 February to 31 July). METHODS: For this country level analysis, we used data on SARS-CoV-2 cases, current and/or cumulative hospitalised COVID-19 patients and current and/or cumulative COVID-19 patients in ICU care. To analyse whether capacities were exceeded, we also retrieved information on the numbers of hospital beds, and on (surge) capacity of ICU beds during the first wave of the COVID-19 pandemic from the COVID-19 Health System Response Monitor (HSRM). Treatment days and mean length of hospital stay were calculated to assess hospital utilisation. RESULTS: Hospital and ICU capacity varied widely across countries. Our results show that utilisation of acute care bed capacity by patients with COVID-19 did not exceed 38.3% in any studied country. However, the Netherlands, Sweden, and Lombardy would not have been able to treat all patients with COVID-19 requiring intensive care during the first wave without an ICU surge capacity. Indicators of hospital utilisation were not consistently related to the number of SARS-CoV-2 infections. The mean number of hospital days associated with one SARS-CoV-2 case ranged from 1.3 (Norway) to 11.8 (France). CONCLUSION: In many countries, the increase in ICU capacity was important to accommodate the high demand for intensive care during the first COVID-19 wave.
Subject(s)
COVID-19 , Critical Care , Europe/epidemiology , Hospital Bed Capacity , Hospitals , Humans , Intensive Care Units , Pandemics , SARS-CoV-2ABSTRACT
INTRODUCTION: Survival after critical illness has noticeably improved over the last decades due to advances in critical care medicine. Besides, there is an increasing number of elderly patients with chronic diseases being treated in the intensive care unit (ICU). More than half of the survivors of critical illness suffer from medium-term or long-term cognitive, psychological and/or physical impairments after ICU discharge, which is recognised as post-intensive care syndrome (PICS). There are evidence-based and consensus-based quality indicators (QIs) in intensive care medicine, which have a positive influence on patients' long-term outcomes if adhered to. METHODS AND ANALYSIS: The protocol of a multicentre, pragmatic, stepped wedge cluster randomised controlled, quality improvement trial is presented. During 3 predefined steps, 12 academic hospitals in Berlin and Brandenburg, Germany, are randomly selected to move in a one-way crossover from the control to the intervention condition. After a multifactorial training programme on QIs and clinical outcomes for site personnel, ICUs will receive an adapted, interprofessional protocol for a complex telehealth intervention comprising of daily telemedical rounds at ICU. The targeted sample size is 1431 patients. The primary objective of this trial is to evaluate the effectiveness of the intervention on the adherence to eight QIs daily measured during the patient's ICU stay, compared with standard of care. Furthermore, the impact on long-term recovery such as PICS-related, patient-centred outcomes including health-related quality of life, mental health, clinical assessments of cognition and physical function, all-cause mortality and cost-effectiveness 3 and 6 months after ICU discharge will be evaluated. ETHICS AND DISSEMINATION: This protocol was approved by the ethics committee of the Charité-Universitätsmedizin, Berlin, Germany (EA1/006/18). The results will be published in a peer-reviewed scientific journal and presented at international conferences. Study findings will also be disseminated via the website (www.eric-projekt.net). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03671447).
Subject(s)
Quality of Life , Telemedicine , Aged , Berlin , Critical Care , Critical Illness , Germany , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVES: This study aimed to determine the prevalence, risk factors of delirium and current practice of delirium management in intensive care units of various levels of care. RESEARCH METHODOLOGY/DESIGN: Prospective multicentre cohort study. SETTING: In all adult patients admitted to one of the participating intensive care units on World Delirium Awareness Day 2018, delirium point and period prevalence rates were measured between ICU admission and seven days after the index day. RESULTS: In total, 28 (33%) Dutch intensive care units participated in this study. Point-prevalence was 23% (range 41), and period-prevalence was 42% (range 70). University intensive care units had a significantly higher delirium point-prevalence compared with non-university units (26% vs.15%, p = 0.02). No significant difference were found in period prevalence (50% vs. 39%, p = 0.09). Precipitating risk factors, infection and mechanical ventilation differed significantly between delirium and non-delirium patients. No differences were observed for predisposing risk factors. A delirium protocol was present in 89% of the ICUs. Mean delirium assessment compliance measured was 84% (±19) in 14 units and estimated 59% (±29) in the other 14. CONCLUSION: Delirium prevalence in Dutch intensive care units is substantial and occurs with a large variation, with the highest prevalence in university units. Precipitating risk factors were more frequent in patients with delirium. In the majority of units a delirium management protocol is in place.
Subject(s)
Delirium , Adult , Cohort Studies , Critical Care , Critical Care Nursing , Humans , Intensive Care Units , Netherlands , Prevalence , Prospective Studies , Risk FactorsABSTRACT
BACKGROUND: Treatment of stroke patients in stroke units has increased and studies have shown improved outcomes. However, a large share of patients in Germany is still treated in hospitals without stroke unit. The effects of stroke unit service line, and total hospital quality certification on outcomes remain unclear. METHODS: We employ annual hospital panel data for 1100-1300 German hospitals from 2006 to 2014, which includes structural data and 30-day standardized mortality. We estimate hospital- and time-fixed effects regressions with three main independent variables: (1) stroke unit care, (2) stroke unit certification, and (3) total hospital quality certification. RESULTS: Our results confirm the trend of decreasing stroke mortality ratios, although to a much lesser degree than previous studies. Descriptive analysis illustrates better stroke outcomes for non-certified and certified stroke units and hospitals with total hospital quality certification. In a fixed effects model, having a stroke unit has a significant quality-enhancing effect, lowering stroke mortality by 5.6%, while there is no significant improvement effect for stroke unit certification or total hospital quality certification. CONCLUSIONS: Patients and health systems may benefit substantially from stroke unit treatment expansion as installing a stroke unit appears more meaningful than getting it certified or obtaining a total hospital quality certification. Health systems should thus prioritize investment in stroke unit infrastructure and centralize stroke care in stroke units. They should also prioritize patient-based 30-day mortality data as it allows a more realistic representation of mortality than admission-based data.
Subject(s)
Hospital Units/standards , Hospitals/standards , Stroke/therapy , Accreditation , Certification , Databases, Factual , Germany/epidemiology , Hospital Mortality , Hospital Units/statistics & numerical data , Hospitals/statistics & numerical data , Humans , Longitudinal Studies , Quality Indicators, Health Care , Stroke/mortality , Treatment OutcomeABSTRACT
BACKGROUND: To determine whether gadolinium-based contrast media (CM) could be used safely for angiographies in patients with renal dysfunction we investigated renal function after gadobutrol exposure and compared the results with standard iodinated CM (iohexol) in a randomized clinical study. METHODS: Twenty-one patients (aged 67+/-11 years, nine female and 12 male) with severely impaired renal function [mean serum creatinine 3.2+/-1.3 mg/dl, mean glomerular filtration rate (GFR) 31+/-16 ml/min/1.73 m(2)] who needed to have angiography because of severe peripheral vascular disease, renal artery stenosis or aortic aneurysms were randomized to receive in a blinded manner either gadobutrol (Gadovist 1.0 mmol/ml) or iohexol (Omnipaque 350) as contrast agents. GFR was measured by CM clearance (Renalyzer) at baseline and 48 h after CM administration. The primary end point was the mean change of GFR from baseline at 48 h, the secondary one the incidence of CM-induced acute renal failure, defined as a decrease in GFR of >50% from baseline within 48 h of CM administration. RESULTS: In the gadobutrol group (n = 10) we observed a statistically significant decrease in GFR of 10.6+/-13.8 ml/min/1.73 m(2) within 48 h after CM administration (P<0.05, paired t test). The incidence of CM-induced ARF amounted to 50%. In comparison, the iohexol group (n = 11) also showed a statistically significant GFR reduction of 8.7+/-8.8 ml/min/1.73 m(2) (P<0.05, paired t test), and of ARF by 45%. The percentile of differences of GFR decreases between the two groups was not significant (P = 0.70). No patient demonstrated other adverse effects of gadobutrol or iohexol administration, apart from GFR reduction. Despite the decline in GFR, no patient required haemodialysis in the 10 following days. CONCLUSIONS: In our study, gadolinium-based angiography showed no benefit over iohexol angiography with respect to preventing GFR reduction in patients with severely impaired renal function.
Subject(s)
Angiography, Digital Subtraction , Contrast Media , Iohexol , Organometallic Compounds , Renal Insufficiency/complications , Uremia/diagnostic imaging , Uremia/etiology , Aged , Aortic Aneurysm/diagnostic imaging , Contrast Media/adverse effects , Double-Blind Method , Female , Gadolinium/adverse effects , Glomerular Filtration Rate/drug effects , Humans , Iohexol/adverse effects , Male , Middle Aged , Organometallic Compounds/adverse effects , Pilot Projects , Renal Artery Obstruction/diagnostic imaging , Renal Insufficiency/physiopathology , Severity of Illness Index , Vascular Diseases/diagnostic imagingABSTRACT
OBJECTIVE: Angiotensin-converting enzyme inhibitors (ACEI) show an antiproteinuric and thus nephroprotective effect in patients suffering from glomerulonephritis. Angiotensin II-receptor-antagonists (AT1RA) are also efficacious in reducing proteinuria. The study was performed to investigate the antiproteinuric effect of AT1RA candesartan in patients diagnosed with chronic glomerulonephritis by biopsy, and who were already being treated with an ACEI. METHODS: A total of 12 patients with a persistent proteinuria of at least 1 g/day who were already being treated with an ACEI for more than 3 months were included. The study was performed using a double-blind, placebo-controlled and randomized method with two treatment periods of 8 weeks (placebo or candesartan 8 mg/day) and a wash-out period of 4 weeks in between. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin- and PAH-clearances at the beginning and the end of each treatment period. RESULTS: Proteinuria significantly decreased from 2 +/- 0.4 g/day to 1.3 +/- 0.3 g/day (P < 0.05) with the addition of candesartan treatment, whereas it remained unchanged (from 1.8 +/- 0.3 g/day to 1.9 +/- 0.3 g/day) under placebo. GFR (candesartan: from 66 +/- 13 to 58 +/- 11 ml/min per 1.73 m2, placebo: from 64 +/- 11 to 62 +/- 13 ml/min per 1.73 m2) and ERPF (candesartan: from 329 +/- 44 to 304 +/- 37 ml/min per 1.73 m2, placebo: from 362 +/- 48 to 315 +/- 46 ml/min per 1.73 m2) did not alter significantly after 8 weeks of treatment. The addition of candesartan treatment significantly reduced systolic blood pressure (from 129 +/- 3 to 123 +/- 2 mmHg, P < 0.05) and diastolic blood pressure (from 79 +/- 2 to 76 +/- 2 mmHg, P < 0.05) compared with placebo (systolic: 128 +/- 3 to 127 +/- 3 mmHg, diastolic: 79 +/- 2 to 79 +/- 2 mmHg). CONCLUSION: Candesartan promotes a complementary antiproteinuric and a small antihypertensive effect after a treatment period of 8 weeks in patients with chronic glomerulonephritis when given in conjunction with an ACEI. Renal hemodynamics did not vary significantly.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Antihypertensive Agents/administration & dosage , Benzimidazoles/administration & dosage , Glomerulonephritis/drug therapy , Proteinuria/drug therapy , Tetrazoles/administration & dosage , Adult , Aged , Angiotensin Receptor Antagonists , Biphenyl Compounds , Blood Pressure/drug effects , Double-Blind Method , Drug Synergism , Female , Glomerular Filtration Rate/drug effects , Glomerulonephritis/physiopathology , Humans , Male , Middle Aged , Proteinuria/physiopathology , Receptor, Angiotensin, Type 1 , Renal Plasma Flow, Effective/drug effectsABSTRACT
BACKGROUND: Nitric oxide (NO) plays an important role in the regulation of blood pressure and renal hemodynamics. METHODS: To further investigate the role of NO in human hypertension, we studied the effect of systemic injection of N(G)-monomethyl-L-arginine (L-NMMA) on renal hemodynamics, urinary sodium excretion (FE(Na)), systemic hemodynamics and several vasoactive hormones in 5 healthy male subjects with (group H) and without (group N) family history of hypertension. An intravenous infusion of L-NMMA (3 mg/kg over 10 min) or placebo was given in a randomized, double-blinded manner. GFR and ERPF were measured by inulin- and PAH-clearances. Norepinephrine infusion (0.1 microg/kg/min over 60 min) served as vasoconstrictive control infusion. RESULTS: L-NMMA induced a significant decrease in ERPF (-135 +/- 49 vs. 7 +/- 31 ml/min/1.73 m(2) with placebo, p < 0.05), a decrease in FE(Na) (-1.2 +/- 0.6% with L-NMMA vs. 0.0 +/- 0.1% with placebo), and a significant increase in diastolic blood pressure (+7 +/- 1 vs. -2 +/- 1 mm Hg with placebo) in group N, only. A sustained drop in plasma renin activity (-0.1 +/- 0.1 vs. 0.3 +/- 0.1 ng/ml/h with placebo) could also be seen in this group, only. Subjects with family history of hypertension showed minor or even no response (changes in diastolic blood pressure: L-NMMA: 5 +/- 3 mm Hg, placebo: 0 +/- 2 mm Hg; changes in ERPF: L-NMMA: -89 +/- 57 ml/min/1.73 m(2), placebo: -34 +/- 28 ml/min/1.73 m(2); changes in plasma renin activity: L-NMMA: -0.0 +/- 0.3 ng/ml/h, placebo: -0.1 +/- 0.2 ng/ml/h). The vasoconstrictive effect of norepinephrine infusion did not differ between both groups. CONCLUSION: Our data indicate that systemic NO synthetase inhibition by L-NMMA results in a blunted effect on systemic blood pressure and the renal hemodynamic system in subjects with family history of hypertension.
Subject(s)
Enzyme Inhibitors/pharmacology , Hemodynamics/drug effects , Hypertension/genetics , Medical Records , Nitric Oxide Synthase/antagonists & inhibitors , Renal Circulation/drug effects , omega-N-Methylarginine/pharmacology , Adult , Angiotensin II/blood , Blood Pressure/drug effects , Double-Blind Method , Endothelin-1/blood , Enzyme Inhibitors/administration & dosage , Heart Rate/drug effects , Humans , Injections, Intravenous , Male , Natriuresis/drug effects , Renin/blood , omega-N-Methylarginine/administration & dosageABSTRACT
Improvement of uremic pruritus was reported under short-term administration of the mu-receptor antagonists naltrexone and naloxone. The aim of the present study was to confirm the efficacy and safety of the oral mu-receptor antagonist naltrexone during a 4-wk treatment period in patients on hemodialysis and peritoneal dialysis. A placebo-controlled, double-blind crossover study of uremic patients with persistent, treatment-resistant pruritus was performed. Of 422 patients screened between December 1997 and June 1998, 93 suffered from pruritus and 23 were eligible for the study. Patients were started either with a 4-wk naltrexone sequence (50 mg/d) or matched placebo. This was followed by a 7-d washout, and patients continued with a 4-wk sequence of the alternate medication. Pruritus intensity was scored daily by a visual analogue scale (VAS) and weekly by a detailed score assessing scratching activity, distribution of pruritus, and frequency of pruritus-related sleep disturbance. Sixteen of 23 patients completed the study. During the naltrexone period, pruritus decreased by 29.2% (95% confidence interval [CI], 18.7 to 39.6) on the VAS and by 17.6% (95% CI, 4.2 to 31.1) on the detailed score. In comparison, pruritus decreased by 16.9% (95% CI, 6.8 to 26.9) on the VAS and by 22.3% (95% CI, 9.3 to 35.2) on the detailed score during the placebo period. The difference between the naltrexone and the placebo treatment period was not statistically significant. Nine of 23 patients complained of gastrointestinal disturbances during the naltrexone period compared with only one of 23 patients during the placebo period (P < 0.05). These results show that treatment of uremic pruritus with naltrexone is ineffective. In addition, a high incidence of adverse effects was observed during treatment with naltrexone.