Long-term Intravenous Administration Research Articles

Influence of Long-Term Continuous Intravenous Administration of Pentoxifylline on Endothelial-Related Coagulation in Critically Ill Patients: Retraction.

Influence of Long-Term Continuous Intravenous Administration of Pentoxifylline on Endothelial-Related Coagulation in Critically Ill Patients: Retraction.

Safety and Effectiveness of Long-term Intravenous Administration of Edaravone for Treatment of Patients With Amyotrophic Lateral Sclerosis

Intravenous edaravone is approved as a disease-modifying drug for patients with amyotrophic lateral sclerosis (ALS), but evidence for efficacy is limited to short-term beneficial effects shown in the MCI186-ALS19 study in a subpopulation in which efficacy was expected. To evaluate the long-term safety and effectiveness of intravenous edaravone therapy for patients with ALS in a real-world clinical setting. Multicenter, propensity score-matched cohort study conducted between June 2017 and March 2020 at 12 academic ALS referral centers associated with the German Motor Neuron Disease Network. Of 1440 patients screened, 738 were included in propensity score matching. Final analyses included 324 patients with ALS comprising 194 patients who started intravenous edaravone treatment (141 received ≥4 consecutive treatment cycles; 130 matched) and 130 propensity score-matched patients with ALS receiving standard therapy. All patients had probable or definite ALS according to the El Escorial criteria, with disease onset between December 2012 and April 2019. Subgroups were defined by applying the MCI186-ALS19 study inclusion criteria to evaluate whether patients would have been considered eligible (EFAS) or ineligible (non-EFAS). Intravenous edaravone plus riluzole vs riluzole only. Patient characteristics and systematic safety assessment for patients who received at least 1 dose of intravenous edaravone. Effectiveness assessment of edaravone was conducted among patients who received at least 4 treatment cycles compared with propensity score-matched patients with ALS who received only standard therapy. Primary outcome was disease progression measured by decrease in the ALS Functional Rating Scale-Revised (ALSFRS-R) score. Secondary outcomes were survival probability, time to ventilation, and change in disease progression before vs during treatment. To account for the matched design, patients receiving edaravone and their corresponding matched controls were regarded as related samples in disease progression analyses; stratification for propensity score quintiles was used for survival probability and time to ventilation analyses. A total of 194 patients started intravenous edaravone treatment; 125 (64%) were male, and the median age was 57.5 years (IQR, 50.7-63.8 years). Potential adverse effects were observed in 30 cases (16%), most notably infections at infusion sites and allergic reactions. Disease progression among 116 patients treated for a median of 13.9 months (IQR, 8.9-13.9 months) with edaravone did not differ from 116 patients treated for a median of 11.2 months (IQR, 6.4-20.0 months) with standard therapy (ALSFRS-R points/month, -0.91 [95% CI, -0.69 to -1.07] vs -0.85 [95% CI, -0.66 to -0.99]; P = .37). No significant differences were observed in the secondary end points of survival probability, time to ventilation, and change in disease progression. Similarly, outcomes between patients treated with edaravone and matched patients did not differ within the EFAS and non-EFAS subgroups. This cohort study using propensity score matching found that, although long-term intravenous edaravone therapy for patients with ALS was feasible and mainly well tolerated, it was not associated with any disease-modifying benefit. Intravenous edaravone may not provide a clinically relevant additional benefit compared with standard therapy alone.

FGF23-related hypophosphatemic osteomalacia induced by long-term intravenous administration of saccharated ferric oxide; a case report

FGF23-related hypophosphatemic osteomalacia induced by long-term intravenous administration of saccharated ferric oxide; a case report

IV/IT hUC-MSCs Infusion in RRMS and NMO: A 10-Year Follow-Up Study.

Background: Stem cell transplantation is emerging as a potential therapeutic strategy in several autoimmune diseases. However, the safety and feasibility of long-term combined intravenous (IV) and intrathecal (IT) administration of hUC-MSCs in relapse remitting multiple sclerosis (RRMS) and neuromyelitis optica (NMO) is largely unknown.Objectives: In this study, we followed up the long-term safety and feasibility of combined IV and IT human umbilical cord mesenchymal stem cells (hUC-MSCs) transplantation in patients with RRMS and NMO.Methods: Five NMO patients and 5 RRMS patients were treated intravenously (4 times) and intrathecally (3 times) over a 21-day period with low-dose allogeneic umbilical cord blood–derived MSCs. All of the patients were monitored regularly by an investigator in a blinded manner to access the Expanded Disability Status Scale, MRI characteristics, and adverse events every 3 months within 12 months and once every year thereafter for 10 years after transplantation.Results: During the long-term follow-up, our data suggested that combined IV and IT administration of hUC-MSCs transplantation is safe and feasible. None of the intolerant adverse events, such as tumor formation and peripheral organ/tissue disorders, were observed throughout the 10-year follow-up.Conclusions: These data suggest that combined intravenous and intrathecal low-dose hUC-MSCs transplantation is safe and feasible in RRMS and NMO patients in the long term. The conclusion requires confirmation by future clinical trials in a larger cohort.

A history of prophylaxis in haemophilia.

: Prophylaxis entails long-term continuous intravenous administration of concentrates of the deficient factor with a view to preventing spontaneous bleeds and the development of hemophilic arthropathy. Initiation of prophylaxis at an early age and continuous uninterrupted factor administration in patients with hemophilia have been hailed as essential by such organizations.The most widely used prophylaxis regimens include the Swedish (Malmö), the Dutch and the Canadian protocols. Different international groups have hailed prophylaxis as the most effective treatment in patients with hemophilia.Prophylaxis is effectiveness in preventing bleeding and arthropathy in children with (particularly early-onset) hemophilia. Although some retrospective trials confirm the benefits of prophylaxis, others point to a lack of conclusive data to support switching adult patients with established hemophilic arthropathy who always received on-demand treatment to prophylactic treatment.The potential effects of prophylaxis on the patients' sex lives, renal status, prostate involvement and cataract must be analyzed before indicating prophylactic treatment in elderly patients.The high efficacy of prophylactic treatment in patients with hemophilia and inhibitors has been widely reported in the literature.

The Nimodipine-Sparing Effect of Perioperative Dexmedetomidine Infusion During Aneurysmal Subarachnoid Hemorrhage: A Prospective, Randomized, Controlled Trial.

Background: Nimodipine can block the influx of calcium into the vascular smooth muscle cell and prevent secondary ischemia in patients with aneurysmal subarachnoid hemorrhage. However, the reduction of blood pressure after long-term intravenous administration of nimodipine has been associated with neurological deterioration. Yet, no effective solutions have been suggested to address this phenomenon. The use of neuroprotective drug combinations may reduce the risk of sudden blood pressure loss. This prospective, randomized, controlled trial was performed to evaluate the nimodipine-sparing effect of perioperative dexmedetomidine infusion during aneurysmal subarachnoid hemorrhage. Methods: One hundred nine patients who underwent aneurysm embolization were divided into three groups: group C (n = 35, infused with 0.9% sodium chloride at the same rate as other two groups), group D1 (n = 38, dexmedetomidine infusion at 0.5 µg·kg–1 for 10 min, then adjusted to 0.2 µg·kg–1·h–1), and group D2 (n = 36, dexmedetomidine infusion at 0.5 µg·kg–1 for 10 min, then adjusted to 0.4 µg·kg–1·h–1). Patient-controlled analgesia was given for 48 h after surgery. The primary outcome measure was the total consumption of nimodipine during the first 48 h after surgery. The secondary outcome measures were recovery time at post-anesthesia care unit (PACU), postoperative pain intensity scores, dexmedetomidine and sufentanil consumption, hemodynamic, satisfaction of patients and neurosurgeon, neurologic examination (Glasgow Coma Scale, GCS), Bruggemann comfort scale, and adverse effects. Intraoperative hemodynamics were recorded at the following time-points: arrival at the operating room (T1); before intubation (T2); intubation (T3); 5 min (T4), 10 min (T5), and 15 min (T6) after intubation; suturing of femoral artery (T7); end of surgery (T8); extubation (T9); and 5 min (T10), 10 min (T11), and 15 min (T12) after arrival at the PACU. The level of sedation was recorded at 15 min, 30 min, 1 h, and 2 h after extubation. We also recorded the incidence of symptomatic cerebral vasospasm during 7 days after surgery, Glasgow Outcome Score (GOS) at 3 months, and incidence of cerebral infarction 30 days after surgery. Results: The consumption of nimodipine during the first 48 h after surgery was significantly lower in group D2 (P < 0.05). Compared with group C, HR and MAP were significantly decreased from T2 to T12 in group D1 and D2 (P < 0.05). Patients in group D2 showed a significantly decreased MAP from T5 to T9 compared with group D1 (P < 0.05). The consumption of sevoflurane, remifentanil, dexmedetomidine, and nimodipine were all significantly reduced in groups D1 and D2 during surgery (P < 0.05). Compared with group C, MAP was significantly decreased in groups D1 and D2 during the first 48 h after surgery (P < 0.05). Compared with group C, consumption of sufentanil and dexmedetomidine at 1 h, pain intensity at 1 h, and 8 h after surgery were significantly decreased in groups D1 and D2 (P < 0.05). FAS was significantly higher in group D2 at 8 h, 16 h, and 24 h after surgery. LOS was significantly lower only in group D2 at 0.5 h after surgery (P < 0.05). Compared with group C, BCS was significantly higher group D2 at 4 h and 8 h after surgery (P < 0.05). There were no significant differences among the three groups in consumption of propofol, cisatracurium, fentanyl, and vasoactive drugs during operation, recovery time at PACU, satisfaction of patients and neurosurgeon, and number of applied urapidil and GCS during the first 48 h after surgery. The incidence of symptomatic cerebral vasospasm during 7 days after surgery, GOS of 3 months, and cerebral infarction after 30 days were also comparable among the three groups. Conclusions: Dexmedetomidine (infusion at 0.5 µg·kg–1 for 10 min, then adjusted to 0.4 µg·kg–1·h–1 during the surgery) significantly reduced the total consumption of nimodipine during the first 48 h after surgery and promoted early rehabilitation of patients although the incidences of symptomatic cerebral vasospasm, GOS, and cerebral infarction were not reduced.

The "Arm-to-Chest Tunneling" technique: A modified technique for arm placement of implantable ports or central catheters.

Central venous catheters or "venous access devices" include totally implantable venous access devices or "ports," peripherally inserted central catheters, and tunneled lines. Venous access devices are now the standard of care in patients requiring long-term intravenous drug administration. Arm venous access device placement is a valuable option for vascular access yet often complicated or rendered practically impossible by the condition and size of peripheral veins. We describe a modification of the arm venous access device implantation technique that we use in our department in order to offer this option to our patients, regardless of their peripheral veins condition. After ultrasound guided venous access of a suitable neck vein, we create a port pouch-in case of a totally implantable vascular access device-or a skin nick-in case of a venous access device-in the inner aspect of the mid-arm. Using a straight metal tunneler, we tunnel the line from the neck to the arm in two stages, externalizing and re-inserting the line into a skin nick made on the deltopectoral groove. We call this technique "Arm-to-Chest Tunneling" and use it to place venous access devices in the arm using a neck venous access. The Arm-to-Chest Tunneling technique allows us to use larger arm venous access device catheters irrespective of the arm veins condition. Thus, this technique has the advantages of arm venous access device placement, with the added benefit of saving the arm veins. The "Arm-to-Chest Tunneling" method offers the alternative to place a venous access device in a more discreet site in the arm, even in cases in which arm veins are inadequate.

A history of prophylaxis in haemophilia.

: Prophylaxis entails long-term continuous intravenous administration of concentrates of the deficient factor with a view to preventing spontaneous bleeds and the development of hemophilic arthropathy. Initiation of prophylaxis at an early age and continuous uninterrupted factor administration in patients with hemophilia have been hailed as essential by such organizations.The most widely used prophylaxis regimens include the Swedish (Malmö), the Dutch and the Canadian protocols. Different international groups have hailed prophylaxis as the most effective treatment in patients with hemophilia.Prophylaxis is effectiveness in preventing bleeding and arthropathy in children with (particularly early-onset) hemophilia. Although some retrospective trials confirm the benefits of prophylaxis, others point to a lack of conclusive data to support switching adult patients with established hemophilic arthropathy who always received on-demand treatment to prophylactic treatment.The potential effects of prophylaxis on the patients' sex lives, renal status, prostate involvement and cataract must be analyzed before indicating prophylactic treatment in elderly patients.The high efficacy of prophylactic treatment in patients with hemophilia and inhibitors has been widely reported in the literature.

Skeletal Site-specific Effects of Zoledronate on in vivo Bone Remodeling and in vitro BMSCs Osteogenic Activity

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone quantity in bone remodeling following injury in the same individuals, shown as increased cortical bone thickness, increased trabecular bone formation and accelerated bone defect repair. We find that the RANKL/OPG ratio and Wnt-3a expression are suppressed at the extracted alveolar sites in Zol-treated rats compared with those at the injured sites of peripheral bones. We also show that Zol-treated bone marrow stromal cell (BMSCs) derived from jaw and peripheral bones exhibit differences in cell proliferation, alkaline phosphatase (ALP) activity, expression of osteogenic and chondrogenic related marker genes, and in vivo bone formation capacity. Hopefully, this study will help us better understand the pathogenesis of BRONJ, and deepen the theoretical research.

Epoprostenol sodium for treatment of pulmonary arterial hypertension.

The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required.

The use of intravenous magnesium in non-preeclamptic pregnant women: fetal/neonatal neuroprotection.

To review the effect of intravenous magnesium in obstetrics on fetal/neonatal neuroprotection. A systematic review of published studies. Five randomized trials and 4 meta-analyses have shown a significant 32% reduction of cerebral palsy when administering magnesium sulfate in case of preterm delivery. The pathophysiologic mechanism is not fully unraveled: modulation of the inflammatory process, both in the mother and the fetus, and downregulation of neuronal stimulation seem to be involved. After long-term high-dose intravenous administration of magnesium, maternal and neonatal adverse effects such as maternal and neonatal hypotonia and osteoporosis and specific fetal/neonatal cerebral lesions have been described. In case of administration for less than 48 h at 1 g/h and a loading dose of 4 g, these toxic amounts are not achieved. American, Canadian and Australian guidelines recommend the use of intravenous magnesium in any threatening delivery at less than 32 weeks. The "number needed to treat" to avoid 1 cerebral palsy is between 15 and 35. Intravenous magnesium significantly reduces the risk for cerebral palsy in preterm birth. Open questions remain the optimal dosing schedule, whether or not repeating when delivery has been successfully postponed and a new episode of preterm labor occurs. Some concern has been raised on a too optimistic value for random error which might have led to over-optimistic conclusions in classic meta-analysis. Randomized trials comparing different doses and individual patient data meta-analysis might resolve these issues.

Percutaneous endovascular salvage techniques for implanted venous access device dysfunction.

Implanted venous access devices (IVADs) are often used in patients who require long-term intravenous drug administration. The most common causes of device dysfunction include occlusion by fibrin sheath and/or catheter adherence to the vessel wall. We present percutaneous endovascular salvage techniques to restore function in occluded catheters. The aim of this study was to evaluate the feasibility, safety, and efficacy of these techniques. Through a femoral or brachial venous access, a snare is used to remove fibrin sheath around the IVAD catheter tip. If device dysfunction is caused by catheter adherences to the vessel wall, a new "mechanical adhesiolysis" maneuver was performed. IVAD salvage procedures performed between 2005 and 2013 were analyzed. Data included clinical background, catheter tip position, success rate, recurrence, and rate of complication. Eighty-eight salvage procedures were performed in 80 patients, mostly women (52.5 %), with a mean age of 54 years. Only a minority (17.5 %) of evaluated catheters were located at an optimal position (i.e., cavoatrial junction ±1 cm). Mechanical adhesiolysis or other additional maneuvers were used in 21 cases (24 %). Overall technical success rate was 93.2 %. Malposition and/or vessel wall adherences were the main cause of technical failure. No complications were noted. These IVAD salvage techniques are safe and efficient. When a catheter is adherent to the vessel wall, mechanical adhesiolysis maneuvers allow catheter mobilization and a greater success rate with no additional risk. In patients who still require long-term use of their IVAD, these procedures can be performed safely to avoid catheter replacement.

Intra-arterial administration of antibiotics for refractory skull base osteomyelitis

We report two cases of elderly diabetic men with skull base osteomyelitis (SBO) originating from malignant external otitis (MEO). In both, a devastating infection and neural paralysis deteriorated after conventional therapy, including long-term intravenous administration of culture-directed antibiotics with strict control of blood sugar levels and surgical debridement of infectious granulation tissue. Since poor perfusion of antibiotics in the lesion may be associated with serious nature of MEO/SBO, we administered antibiotics intra-arterially via a retrograde catheter with the tip set at the proximal point of the external carotid artery to increase the tissue drug concentration in the maxillary artery (MA) and ascending pharyngeal artery (APA) supply areas, in which intense inflammation was observed. This intra-arterial administration of antibiotics (IA therapy) followed by long-term intravenous and oral antibiotic treatments eliminated their infection and no recurrence was observed in 2 years follow-up period. Interestingly, CT images of angiography via the catheter demonstrated stronger enhancement in the MA supply area compared to the APA supply area and IA therapy was more effective in the former. These results suggest that IA therapy, which might achieve high antibiotic concentration at the site of infection, is effective in patients with MEO/SBO refractory to conventional treatments.

English

Pyogenic liver abscess is a serious disease, which is potentially fatal if left untreated. In developed countries, pyogenic abscesses are the most common but worldwide, amoebae are the most common cause. We report a 60-year-old diabetic woman with a 2 months history of pain abdomen, 1 month history of high fever and anorexia who had multiple liver abscess caused by anaerobic Actinomyces species and Enterococcus faecalis and was complicated by peritonitis. Treatment included prompt percutaneous drainage coupled with long-term intravenous administration of Amikacin, Metronidazole and Piperacillin/ Tazobactum. The patient later died due to peritonitis.

Post‐traumatic Pseudallescheria apiosperma osteomyelitis: positive outcome of a young immunocompetent male patient due to surgical intervention and voriconazole therapy

The present case describes thesuccessful treatment of an immunocompetent youngmale patient suffering from a severe, post-traumaticPseudallescheria apiosperma osteomyelitis of the tibia.Cure of the patient was achieved by long-termvoriconazole administration and surgical debridementof infected soft tissue and bone.

One-Day Antibiotic Infusion for the Prevention of Postoperative Infection Following Arthroplasty: A Case Control Study

Intravenous antibiotics effectively reduce the prevalence of postoperative infection. However, Japanese orthopaedic surgeons have no consensus with regard to the optimal duration of prophylaxis. The aim of this study is to compare the outcome of one-day intravenous antibiotic administration with that of long-term intravenous antibiotic administration. Patients who underwent total hip or knee arthroplasty were divided into 2 groups to receive one of 2 prophylactic protocols retrospectively. Group A (223 patients) received intravenous antibiotics twice only on the day of surgery, whereas Group B (104 patients) received intravenous antibiotics for at least 3 days after surgery. We analyzed the wound infection rate and monitored liver and renal functions. None of these patients had a postoperative infection. No liver dysfunction and renal dysfunction were observed. One-day antibiotic infusion was as effective as long-term antibiotics in preventing infection after arthroplasty and achieved greater cost effectiveness.

Woman With Hip Pain

A 32-year-old woman with mitral valve prolapse presented to our emergency department with 24 hours of worsening left hip pain exacerbated by movement and weight bearing. She had no other systemic, infectious, or rheumatologic symptoms. Physical examination revealed no local signs of inflammation, but pain was reproducible with passive range of motion. Movement of her other joints did not cause pain. The plasma WBC count was 9,600/mL3, with 87% neutrophils, and the C-reactive protein concentration was 1.5 mg/dL. Pelvic and hip radiograph results were normal. Bedside ultrasonography identified a left hip effusion (Figure 1). Synovial aspiration yielded turbid fluid without crystals and a WBC count of 98,000/mL3 (99% neutrophils). An orthopedic surgeon performed arthrotomy and operative washout. The effusion recurred during the postoperative period, so the patient was taken back to the operating room 3 days later for repeated arthrotomy. She was transferred to another facility on hospital day 4 for long-term intravenous administration of antibiotics. The emergency physician can diagnose hip effusion with bedside ultrasonography, using the following technique: With the patient supine and the hip in internal rotation and slight flexion, position a linear probe on the anterior surface, across the joint in a sagittal plane. An effusion will appear as a hypoechoic (dark) layer adjacent to the femoral cortex.1Lee F.M. Fox J.C. Diagnosis of hip effusion with bedside ultrasound in the emergency department.West J Emerg Med. 2003; 4: 51-54Google Scholar The uninvolved opposite joint can provide a normal comparison (Figure 2). Once a joint effusion is identified, an arthrocentesis can be performed with real-time ultrasonographic guidance.

Two Cases of Intractable Malignant External Otitis with Skull Base Osteomyelitis Alleviated by Intraarterial Antibiotic Administration

Malignant external otitis (MEO) is a devastating external auditory canal infection usually occurring in the elderly with diabetes. MEO often progresses to potentially lethal skull base osteomyelitis (SBO) complications such as meningitis or multiple cranial nerve palsies. Poor vascularity in affected tissue due to diabetic microangiopathy and Pseudomonal infection is thought responsible for refractory infection. We conducted intraarterial antibiotic infusion (IA) in the external carotid artery of two subjects with intractable MEO deteriorating after long-term intravenous antibiotic administration with surgical debridement. IA raised the antibiotic concentration in infectious tissue. Clinical MEO manifestation was relieved just after starting IA, and IA therapy was followed by additional long-term intravenous and oral antibiotic administration, dramatically improving MEO while leaving only minimal infection at the skull base. These results demonstrate IA effectiveness in treating refractory MEO.

Urinary Lipocalin-Type Prostaglandin D Synthase: A Potential Marker for Early Gentamicin-Induced Renal Damage?

Urinary excretion of lipocalin-type prostaglandin D synthase (L-PGDS) has been suggested to be a useful biomarker of early diabetic nephropathy. We studied whether L-PGDS is also a marker of gentamicin (GM)-induced renal damage in the "creatinine-blind" range. A prospective study was conducted in 6 patients who were given long-term intravenous administration of GM (18-42 days in combination with a beta-lactam/carbapenem antibiotic or vancomycin) for the treatment of infective endocarditis. Urinary excretions of L-PGDS, beta2-microglobulin, and N-acetyl-beta-D-glucosaminidase were measured in the early (within 10 days from commencement) and late (thereafter) phases of GM therapy. Systemic clearance of GM (CLGM) and creatinine clearance (CLcr) was also measured concomitantly. CLGM was reduced significantly (P < 0.05) by 10% from the early to late treatment phase, whereas urinary L-PGDS excretion showed a significant (P < 0.05) increase (from 7.3 +/- 4.6 to 8.7 +/- 5.0 mg/g creatinine, mean +/- SD) concomitantly. In contrast, no significant changes were observed for urinary beta2-microglobulin and N-acetyl-beta-D-glucosaminidase concentrations. In conclusion, urinary L-PGDS may be a promising biomarker for the early phase of GM-induced renal impairment.

Effects of Long-Term Intravenous Administration of Adrenomedullin (AM) Plus hANP Therapy in Acute Decompensated Heart Failure A Pilot Study

It was reported previously that 30 min administration of adrenomedullin (AM) improves hemodynamics in chronic stable heart failure patients. The present study was designed to examine whether long-term AM + human atrial natriuretic peptide (hANP) administration can be used as a therapeutic drug in patients with acute decompensated heart failure (ADHF) in clinical setting. Seven acute heart failure patients (74 +/- 5 years) with dyspnea and pulmonary congestion were studied. AM (0.02 microg x kg(-1) x min(-1)) + hANP (0.05 microg x kg(-1) x min(-1)) was infused for 12 h and then hANP (0.05 microg x kg(-1) x min(-1)) was infused for 12 h. Hemodynamic, renal, hormonal and oxidative stress responses were evaluated. AM + hANP significantly reduced mean arterial pressure, pulmonary arterial pressure and systemic and pulmonary vascular resistance without changing heart rate, and increased cardiac output for most time-points compared with those at baseline. In addition, AM + hANP reduced aldosterone, brain natriuretic peptide and free-radical metabolites compared with those at baseline (all P<0.05). AM + hANP increased urine volume and U(Na)V compared with baseline data. In this small, pilot trial, AM + hANP therapy had beneficial hemodynamic and hormonal effects in ADHF. Intravenous infusion of AM with hANP could be used as a therapeutic drug in ADHF. These data are preliminary and require confirmation in a larger clinical study.