Low-dose Dopamine Research Articles

Neurohormonal Effects of Intravenous Dopamine in Patients with Acute Heart Failure

Background/Objectives: Many clinical trials have shown beneficial effects of low-dose dopamine on renal function, diuresis and symptom relief, or cardiac function in hospitalized patients with acute decompensated heart failure (HF). The aim is to assess the neurohormonal effects and the effects on clinical outcomes of the addition of low-dose dopamine in furosemide treatment in patients hospitalized for acute decompensated HF. Methods: A total of 62 patients hospitalized for acute decompensation of HF, were randomly allocated to one of the following three groups: i. LDF (low-dose furosemide), ii. HDF (high-dose furosemide) and, iii. LDFD (low-dose furosemide and dopamine). Primary outcomes of the present analysis were biochemical and neurohormonal indices (i.e., urea, creatinine, hemoglobin, electrolytes, natriuretic peptides, troponin, renin, angiotensin, aldosterone, adrenaline, noradrenaline). Secondary endpoints included clinical outcomes (i.e., length of stay, in-hospital mortality, 2-month mortality and rehospitalization, and 1-year mortality and rehospitalization). Results: Urea and creatinine levels were similar for each day among the three groups (p > 0.05). The amount of urine was similar among the three groups per measurement at 2, 4, 6 and at 8 h (p > 0.05). Biochemical and neurohormonal indices as well as clinical outcomes did not differ among patients receiving different doses of furosemide, nor in patients receiving furosemide in combination with dopamine (p > 0.05). Conclusions: Although the addition of low-dose dopamine to intravenous furosemide was considered to have some theoretical advantages in maintaining renal function, no significant differences in neurohormonal effects and clinical outcomes were observed in patients hospitalized for acute decompensation of HF.

Peripheral chemoreflex restrains skeletal muscle blood flow during exercise in participants with treated hypertension.

We tested the hypothesis that in human hypertension, an increased tonicity/sensitivity of the peripheral chemoreflex causes a sympathetically mediated restraint of nutritive blood flow to the exercising muscles. Fourteen patients with treated hypertension (age 69±11 years, 136±12/80±11mmHg; mean±SD) were studied under conditions of intravenous 0.9% saline (control) and low-dose dopamine (2µgkg-1min-1) to inhibit the peripheral chemoreflex, at baseline, during isocapnic hypoxic rebreathing and during rhythmic handgrip exercise (3min, 50% maximum voluntary contraction). At baseline, dopamine did not change mean blood pressure (95±10 vs. 98±10mmHg, P=0.155) but increased brachial artery blood flow (59±20 vs. 48±16mlmin-1, P=0.030) and vascular conductance (0.565±0.246 vs. 0.483±0.160mlmin-1mmHg-1; P=0.039). Dopamine attenuated the increase in mean blood pressure (∆3±4 vs. ∆8 ±6mmHg, P=0.007) to isocapnic hypoxic rebreathing and reduced peripheral chemoreflex sensitivity by 28±37% (P=0.044). Rhythmic handgrip exercise induced increases in brachial artery blood flow and vascular conductance (both P<0.05 vs. rest after 45s) that were greater with dopamine than saline (e.g. Δ76±54 vs. Δ60±43mlmin-1 and Δ0.730±0.440 vs. Δ0.570±0.424mlmin-1mmHg-1, respectively, at 60s; main effect of condition both P<0.0001). Our results indicate that the peripheral chemoreflex is tonically active at rest and restrains the blood flow and vascular conductance increases to exercise in treated human hypertension. KEY POINTS: It was hypothesised that in human hypertension, an increased tonicity/sensitivity of the peripheral chemoreflex causes a sympathetically mediated restraint of nutritive blood flow to the exercising muscles. Treated patients with hypertension (n=14) were studied under conditions of intravenous 0.9% saline (control) and low-dose dopamine (2 µgkg-1min-1) to inhibit the peripheral chemoreflex. Low-dose dopamine reduced resting ventilation and peripheral chemoreflex sensitivity, and while mean blood pressure was unchanged, brachial artery blood flow and vascular conductance were increased. Low-dose dopamine augmented the brachial artery blood flow and vascular conductance responses to rhythmic handgrip. These findings indicate that the peripheral chemoreflex is tonically active at rest and restrains the blood flow, and vascular conductance increases to exercise in treated human hypertension.

Donor Conditioning and Organ Pre-Treatment Prior to Kidney Transplantation: Reappraisal of the Available Clinical Evidence.

Therapeutic measures aimed at optimising organ function prior to transplantation-whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal-have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a favourable effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion, in particular, has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy and therapeutic donor hypothermia in the intensive care unit after brain death confirmation, have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to benefits for graft survival, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence from large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.

Circulatory Effects of Peripheral Chemoreflex Inhibition During Exercise in Treated Hypertension

The sensitization of the peripheral (carotid) chemoreflex can cause a sympathetically mediated restraint of blood flow to the exercising muscles in some disease states (e.g., heart failure, COPD). Such impairments in nutritive blood flow have the potential to impair exercise tolerance and raise exercising blood pressure (BP). Increased peripheral chemoreflex sensitivity and pronounced exercise-induced surges in BP have been reported in hypertension. Herein, we tested the hypothesis that suppressing peripheral chemoreflex sensitivity improves skeletal muscle blood flow during exercise in hypertension. Fourteen patients with treated hypertension (age 69±11 years, systolic BP 136±12 mmHg, diastolic BP 80±11 mmHg; mean ± SD) performed a resting baseline (3 min), an isocapnic hypoxia rebreathing test and rhythmic handgrip exercise (3 min at 50% of maximal voluntary contraction, 1 s contraction and 2 s relaxation) with either intravenous 0.9% saline (control) or low-dose dopamine (2 mcg·kg−1·min−1) to inhibit the peripheral chemoreflex. BP (finger plethysmography), heart rate (HR; electrocardiogram) and ventilation (V̇E; heated pneumotachometer) were recorded throughout. Brachial artery blood flow was monitored (duplex Doppler ultrasound) at rest (1 min average) and during handgrip (15 s averages), and vascular conductance calculated as brachial blood flow/mean BP. Dopamine blunted the peak (last 15 s) increase in V̇E during isocapnic hypoxic rebreathing compared to saline infusion (Δ6±6 vs. Δ9±5 L·min−1, P=0.026), while also attenuating peak mean BP (Δ3±4 vs. Δ8±6 mmHg, P=0.007). Dopamine did not change resting mean BP (95±10 vs. 98±10 mmHg, P=0.155) and HR (68±7 vs. 66±8 beats·min−1, P=0.100). However, dopamine increased resting brachial blood flow (59±20 vs. 48±16 mL·min−1, P=0.030) and vascular conductance (0.565±0.246 vs. 0.483±0.160 mL·min−1·mmHg−1, P=0.039) and decreased resting V̇E (10.5±3.2 vs. 11.5±3.1 L·min−1, P=0.036) versus saline. Handgrip increased brachial artery blood flow (p&lt;0.05 vs. rest after 45 s), vascular conductance (p&lt;0.05 vs. rest after 45 s) in both saline and dopamine trials, while mean BP, HR and V̇E were unchanged (main effect of time P=0.829, P=0.954 and P=0.255, respectively). Notably, brachial artery blood flow (e.g., Δ76±54 vs. Δ60±43 mL·min−1 at 60 s) and vascular conductance (e.g., Δ0.730±0.440 vs. Δ0.570±0.424 mL·min−1·mmHg−1 at 60 s) responses to handgrip were greater with dopamine than saline (main effect of condition both p&lt;0.0001). Collectively, these findings indicate that the use of low-dose dopamine to suppress peripheral chemoreflex sensitivity improves skeletal muscle blood flow during rhythmic handgrip exercise in patients with treated hypertension. Funding support provided by the Health Research Council of New Zealand (19/687) and the Sidney Taylor Trust. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of Tolvaptan Combined with Low-Dose Dopamine in Heart Failure Patients with Acute Kidney Injury.

The impact of tolvaptan and low-dose dopamine on heart failure (HF) patients with acute kidney injury (AKI) remains uncertain from a clinical standpoint.HF patients with AKI were selected and divided in a 1:1 fashion into the dopamine combined with the tolvaptan group (DTG), the tolvaptan group (TG), and the control group (CG). According to the standard of care, TG received tolvaptan 15 mg orally daily for a week. DTG received combination treatment, including 7 consecutive days of dopamine infusion (2 μg/kg・minutes) and oral tolvaptan 15 mg. Venous blood and urine samples were taken before and after therapy. The primary endpoint was the cardiorenal serological index after 7 days of treatment.Sixty-five patients were chosen randomly for the DTG (22 patients), TG (20 patients), and CG (23 patients), which were similar before the treatment. The serum indexes related to cardiac function (N-terminal probrain natriuretic peptide and cardiac troponin I) in DTG were decreased, compared with TG and CG (P < 0.05). Furthermore, the serological markers of renal function (serum cystatin C, serum creatinine, and neutrophil gelatinase-associated lipocalin) in DTG were lower than those in TG and CG (P < 0.05). There was no significant difference in the incidence of adverse reactions among groups.Low-dose dopamine combined with tolvaptan can markedly improve patients' cardiac and renal function. This may be considered a new therapeutic method for HF patients with AKI.

Prognostic Significance of Blood Pressure at Rest and After Performing the Six-Minute Walk Test in Patients With Acute Heart Failure.

It remains unclear whether systolic (SBP) and diastolic (DBP) pressure and BP response after six-minute walk test (6MWT) are associated with adverse outcomes in patients with acute heart failure (AHF). We investigated these associations in 98 AHF patients (24.5% women; mean age, 70.5 years) enrolled in the ROSE trial (The Low-dose Dopamine or Low-dose Nesiritide in Acute Heart Failure with Renal Dysfunction). The primary endpoint consisted of any death or rehospitalization within 6 months after randomization. We computed hazard ratios (HRs) of the risks associated with 1-SD increase in post-exercise BP levels and BP ratios, calculated as BP immediately after 6MWT divided by BP before 6MWT. The BP before and after 6MWT averaged 110.6/117.5 mm Hg for SBP and 61.9/64.7 mm Hg for DBP. In multivariable-adjusted analyses including clinic BP measured at the same day of 6MWT, higher DBP after 6MWT was associated with lower risk of the primary endpoint (HR, 0.49; 95% confidence interval [CI], 0.26-0.95; P = 0.034). Both higher SBP and DBP immediately after 6MWT were associated with lower risk of 6-month mortality (HRs, 0.39/0.16; 95% CI, 0.17-0.90/0.065-0.40; P ≤ 0.026). The post-exercise SBP ratio was associated with the risk of 6-month mortality in multivariable-adjusted analyses (HR, 0.44; P = 0.023). Higher BP levels and BP ratios immediately after 6MWT conferred lower risk of adverse health outcomes. Our observations highlight that 6MWT-related BP level and response may refine risk estimates in patients hospitalized AHF and may help further investigation for the development of HF preventive strategies.

Clinical and genetic analysis of tyrosine hydroxylase deficiency of six cases

The clinical and molecular genetic data of 6 patients with genetically confirmed tyrosine hydroxylase deficiency(THD) diagnosed in Department of Neurology, Qilu Hospital of Shandong University from March 2017 to February 2022 were retrospectively collected and analyzed. The 6 patients were from 5 families. Among them, 5 patients had persistent or paroxysmal abnormal walking posture, 4 patients had dystonia of head and face, including spasm of perioral and oculopharyngeal muscles, hyperactivity, and binocular upvision, 4 patients showed obvious morning light and evening heavy phenomenon, 2 patients had postural tremor of limbs, 2 patients had psychomotor retardation from childhood, 1 patient only had limb and cervical muscle weakness, 1 patient had epileptic seizures. Of the 6 patients, only 1 was adult-onset, and the rest were child-onset. Four patients had good response to low-dose dopa preparation, 2 patients from the same family had poor response to dopamine treatment, requiring extremely low dose initiation and multi-frequency titration treatment. However, the long-term treatment effect was poor with obvious abnormalities. Gene testing of 5 families revealed 8 mutations in the TH gene, with c.698G>A (p.R233H) being the hot spot mutation site. The clinical manifestations of THD are complex. Besides paroxysmal or persistent dystonia, it can also be accompanied by eye movement crisis, muscle weakness, epilepsy, and delayed mental and motor development. Most patients respond well to low-dose dopamine preparations, but a small number of patients require titration treatment with extremely low-dose dopamine preparations, and the long-term effect is not satisfactory.

Dialysis Termination and Dialysis Dose in Severe Intra-Dialytic Hypotension Managed with Inotropic Support in a Low Income Setting

Background: Intradialytic Hypotension (IDH) still remains a major complication and burden, and is associated with inadequate dose, poor quality of life, increased morbidity and mortality. Inotropic support could minimize dialysis termination and improve the dialysis dose. Objective: To determine the impact of inotropic support on the incidence of dialysis termination (a common finding in resource limited settings), and the dialysis dose. Materials and Methods: This retrospective, observational study compared the dialysis outcome in severe IDH with, and without dopamine treatment. Results: The 36 participants had 518 sessions with IDH, of this, 405 (78.19%) were without dopamine while 113 (21.81%), with severe IDH, were managed with dopamine. The mean ages of participants in the two groups were not significantly different, P=0.05. The risk of severe IDH was negatively related to the predialysis systolic blood pressure (SBP) P=0.03 while the postdialysis. Blood pressure was higher in dopamine treated sessions (DTSs). The blood flow rate (BFR) and dialysis dose were higher in the DTSs (P=0.05) and (P=0.04), but the dialysis dose was lower with anemia (P&lt;0.001), metabolic acidosis (P&lt;0.001), heart failure (0.04) and diabetes (P=0.04). In DTSs, females were more likely to have lower dialysis doses, (P=0.02). Independent associates of inadequate dialysis dose were infrequent dialysis sessions, infrequent erythropoietin doses, metabolic acidosis and anemia. Conclusion: Managing severe intradialytic hypotension with low dose dopamine is associated with reduced frequency of dialysis termination and augmentation of the dialysis dose. Reductions in the intradialytic BP gradients could minimize the complications associated with wide intradialytic BP variations. Keywords: Inotropic support, Dopamine, Severe intradialytic hypotension, Dialysis dose, Dialysis termination, Tachycardia, Heart failure, Blood flow rate.

Titrated segmental epidural anesthesia for bilateral total knee replacement in a patient with severe aortic stenosis and severe bilateral carotid artery stenosis: a case report

BackgroundTotal knee replacement is a major orthopedic procedure for severe, painful, and mobility-limiting knee arthritis. Aortic valve stenosis is the most frequent valvular heart disease and the most commonly performed valvular procedure. Stenosis of the valve may lead to left ventricular hypertrophy, ventricular dysfunction, myocardial ischemia, and a state of fixed cardiac output. Changes in hemodynamic parameters such as hypotension and bradycardia in patients with carotid artery stenosis may lead to cerebrovascular accidents, especially during anesthesia.Case presentationA 76-year-old woman with a 6-year history of bilateral knee pain. The pain was dull, aching, and severe in intensity, and it prevented her from sleeping despite optimal analgesics. A general physical examination revealed an elderly, frail woman in mild respiratory distress. She had bilateral small-volume radial pulses, positive hepatojugular reflux, and heart sounds of S1, S2, and S4 with an ejection systolic murmur, and carotid bruits were heard bilaterally. Epidural anesthesia was done by injection of 2.5 mL of 0.5% plain bupivacaine in aliquots every 5 min until the level of the block reached the suprapubic region (titrated segmental epidural anesthesia). The patient was not preloaded with intravenous fluid prior to the establishment of epidural anesthesia, and the epidural anesthesia-induced hypotension that may ensue was managed with intraoperative dopamine infusion at 5 µg/kg/min.ConclusionsTitrated segmental epidural anesthesia with intraoperative infusion of low-dose dopamine reduces the perioperative risk of myocardial infarction, cerebrovascular accident, and neurocognitive deficit in a patient with severe aortic stenosis and severe bilateral carotid stenosis.

Levodopa-refractory hyperprolactinemia and pituitary findings in inherited disorders of biogenic amine metabolism.

Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa-refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty-six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5-30, 1st-3rd quartiles: 12.25-17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation-related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia-related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow-up evaluations. The potential of slow-release levodopa formulations and low-dose dopamine agonists as part of first-line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia-related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism.

Low-dose dopamine improves ventilatory efficiency during exercise in heart failure with preserved ejection fraction through inhibition of tonic activity of peripheral chemoreceptors

Abstract Introduction Peripheral chemoreceptors (PChRs) play an important role in adequate oxygenation by 1) maintaining baseline ventilation (tonic activity) and 2) providing hyperventilation in response to acute hypoxia (reflexia). It has been previously shown that in patients with heart failure with reduced ejection fraction hypertonicity and/or hyperreflexia of PChRs contribute to exercise intolerance (ExIn). It is unknown whether similar mechanisms are present in heart failure with preserved ejection fraction (HFpEF) and which component of PChR functionality has a decisive role in this matter. Purpose The aim of this study was to evaluate the role of PChRs in ExIn in patients with HFpEF. Methods All patients underwent assessment of PChRs which included measurements of: 1) tonic activity (TA, decrease in ventilation following pharmacological inhibition of PChRs), 2) reflex response (RR; an increase in ventilation in the response to acute hypoxia). The inhibition of PChRs was achieved with low-dose dopamine infusion (3 μg kg–1 min–1) and the acute hypoxia was produced with brief nitrogen gas administrations. Enrolled patients underwent symptom-limited cardiopulmonary exercise test using cycle ergometer from which peak oxygen consumption (peakVO2) and the slope relating ventilation to carbon dioxide (VE/VCO2 slope) were derived. All measurements (including PChRs' function tests and cardiopulmonary exercise test) were performed twice in a randomized, double-blinded and placebo-controlled manner (dopamine vs normal saline). Results We included 12 stable patients with HFpEF (age: 73±7 years, LVEF: 58±3%). During exercise the inhibition of PChRs with dopamine resulted in the improvement (decrease) in VE/VCO2 slope comparing to placebo (36±3.6 vs 34.3±3.7, p=0.04) but no change regarding peakVO2. There was a correlation between TA and relative magnitude of improvement in VE/VCO2 following PChRs inhibition (R=0.76, p=0.005). We also found a trend for correlation between RR and VE/VCO2 measured during placebo (R=0.56, p=0.059). There was no correlation between TA and RR (p=0.24). Conclusion Both TA and RR of PChRs are involved in ventilatory inefficacy during exercise in HFpEF – but in different ways. While augmented RR is likely an indicator of high VE/VCO2, the elevated TA indicates the magnitude of the improvement in exercise tolerance following PChRs deactivation. Thus, further interventions aimed at the modulation of PChRs should enroll patients based on TA rather than RR. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Science Centre, PRELUDIUM grant

Dealing With Failure.

Dealing With Failure.

Inhibition of peripheral chemoreceptors improves ventilatory efficiency during exercise in heart failure with preserved ejection fraction − a role of tonic activity and acute reflex response

Peripheral chemoreceptors (PChRs) play a significant role in maintaining adequate oxygenation in the bloodstream. PChRs functionality comprises two components: tonic activity (PChT) which regulates ventilation during normoxia and acute reflex response (peripheral chemosensitivity, PChS), which increases ventilation following a specific stimulus. There is a clear link between augmented PChS and exercise intolerance in patients with heart failure with reduced ejection fraction. It has been also shown that inhibition of PChRs leads to the improvement in exercise capacity. However, it has not been established yet: 1) whether similar mechanisms take part in heart failure with preserved ejection fraction (HFpEF) and 2) which component of PChRs functionality (PChT vs. PChS) is responsible for the benefit seen after the acute experimental blockade. To answer those questions we enrolled 12 stable patients with HFpEF. All participants underwent an assessment of PChT (attenuation of minute ventilation in response to low-dose dopamine infusion), PChS (enhancement of minute ventilation in response to hypoxia) and a symptom-limited cardiopulmonary exercise test on cycle ergometer. All tests were placebo-controlled, double-blinded and performed in a randomized order. Under resting conditions and at normoxia dopamine attenuated minute ventilation and systemic vascular resistance (p = 0.03 for both). These changes were not seen with placebo. Dopamine also decreased ventilatory and mean arterial pressure responses to hypoxia (p < 0.05 for both). Inhibition of PChRs led to a decrease in V˙E/V˙CO2 comparing to placebo (36 ± 3.6 vs. 34.3 ± 3.7, p = 0.04), with no effect on peak oxygen consumption. We found a significant relationship between PChT and the relative decrement of V˙E/V˙CO2 on dopamine comparing to placebo (R = 0.76, p = 0.005). There was a trend for correlation between PChS (on placebo) and V˙E/V˙CO2 during placebo infusion (R = 0.56, p = 0.059), but the relative improvement in V˙E/V˙CO2 was not related to the change in PChS (dopamine vs. placebo). We did not find a significant relationship between PChT and PChS. In conclusion, inhibition of PChRs in HFpEF population improves ventilatory efficiency during exercise. Increased PChS is associated with worse (higher) V˙E/V˙CO2, whereas PChT predicts an improvement in V˙E/V˙CO2 after PChRs inhibition. This results may be meaningful for patient selection in further clinical trials involving PChRs modulation.

Intraoperative low-dose dopamine is associated with worse survival in patients with hepatocellular carcinoma: A propensity score matching analysis.

BackgroundDopamine is widely used in patients during surgery. We evaluated the association between intraoperative low-dose dopamine administration and recurrence-free survival (RFS) and overall survival (OS) in patients with hepatocellular carcinoma (HCC).MethodsConsecutive patients with nonmetastatic HCC who underwent radical hepatectomy were enrolled between 2008 and 2010. Univariate and multivariate logistic regression analyses were used to evaluate the prognostic factors for RFS and OS. Survival outcomes were evaluated using Kaplan–Meier analyses with the log-rank test. A one-to-one propensity score matching (PSM) analysis was performed to reduce confounding bias.ResultsA total of 805 HCC patients, including 699 patients who did not receive dopamine consumption and 106 patients who received low-dose dopamine during the operation, were retrospectively analyzed. The patients who were assigned low-dose dopamine had worse RFS (p = 0.009) and OS (p = 0.041) than those who did not receive dopamine. Multivariate regression analysis showed that the intraoperative administration of low-dose dopamine was an independent unfavorable predictor for RFS (p = 0.004) but not for OS (p = 0.059). After PSM, the low-dose dopamine-treated group still had significantly poorer RFS (p = 0.003) and OS (p = 0.002). When stratified by time of recurrence, patients with low-dose dopamine use had a significantly greater chance of recurrence within 2 years (p = 0.007) but not after 2 years (p = 0.186).ConclusionsIntraoperative low-dose dopamine use has a negative impact on RFS and OS in HCC patients who have undergone radical hepatectomy. Further prospective studies are required to assess the effects of low-dose dopamine on surgical outcomes in HCC patients.

The dilemma of polypharmacy in psychosis: is it worth combining partial and full dopamine modulation?

Antipsychotic polypharmacy in psychotic disorders is widespread despite international guidelines favoring monotherapy. Previous evidence indicates the utility of low-dose partial dopamine agonist (PDAs) add-ons to mitigate antipsychotic-induced metabolic adverse effects or hyperprolactinemia. However, clinicians are often concerned about using PDAs combined with high-potency, full dopaminergic antagonists (FDAs) due to the risk of psychosis relapse. We, therefore, conducted a literature review to find studies investigating the effects of combined treatment with PDAs (i.e. aripiprazole, cariprazine and brexpiprazole) and FDAs having a strong D2 receptor binding affinity. Twenty studies examining the combination aripiprazole – high-potency FDAs were included, while no study was available on combinations with cariprazine or brexpiprazole. Studies reporting clinical improvement suggested that this may require a relatively long time (~11 weeks), while studies that found symptom worsening observed this happening in a shorter timeframe (~3 weeks). Patients with longer illness duration who received add-on aripiprazole on ongoing FDA monotherapy may be at greater risk for symptomatologic worsening. Especially in these cases, close clinical monitoring is therefore recommended during the first few weeks of combined treatment. These indications may be beneficial to psychiatrists who consider using this treatment strategy. Well-powered randomized clinical trials are needed to derive more solid clinical recommendations.

Low-Dose Dopamine in the Management of Intradialysis Hypotension: A Retrospective Cohort Study in Nigeria

Introduction: Intradialytic hypotension (IDH) still remains a common finding in maintenance haemodialysis despite improvements in dialysis delivery. Measures are needed to minimise some aftermath of IDH like dialysis termination, which can impact poorly on dialysis outcome. Methods: This retrospective study assessed IDH in a low-income setting, and compared two cohorts of IDH with and without dopamine treatment. Results: Of the 416 participants, 92 (22.1%) had at least an episode of symptomatic IDH. Of these, 20 (21.7%) were treated with dopamine. Of the 2,205 sessions, 468 (21.2%) had symptomatic IDH, of which 63 (13.4%) with severe IDH were treated with dopamine. The mean age of all participants and dopamine treatment participants were 50.8 ± 9.3 years and 64.6 ± 9.5 years, respectively (P=0.001). Blood pressure (BP) reductions following dialysis were more with females (P=0.04). Dialysis dose was adequate in 7.9% and 4.2% of sessions with and without dopamine (P&lt;0.001). Improvements in glomerular filtration rate were greater in dopamine-treated sessions (P=0.03 and P=0.04, respectively). Fewer anti-hypertensives (aOR: 14.64; 95% confidence interval [CI]: 7.88–20.41), low predialysis systolic (aOR:5.59; 95% CI: 3.88–9.41), and diastolic blood pressure (aOR: 5.78; 95% CI: 4.06-9.81) were independently associated with dopamine-treated sessions. Conclusion: IDH was found in 21.2% of dialysis sessions. 13.4% with severe IDH had dopamine treatment. Participants with dopamine-treated sessions had fewer dialysis terminations and hospitalisations, and dopamine treatment improved the prescribed dialysis and gave higher dialysis doses. Considering the economic effects of dialysis termination in low-income nations, intradialytic dopamine could be very beneficial.

Dopamine Adjustment Difficulties in Special Pathophysiological Conditions

Dopamine is a commonly used drug but its biology and cellular action is not well known, its bizarre actions in neonates back to different pattern of receptors on vascular and metabolic excretion rate especially in preterm babies.[1] Dopamine’s physiological action is dose dependent and give maximum diuresis and natriuresis at the dose of 2 micrograms/kg/min compared to 4 micrograms/ kg/min in neonates.[2] Such physiological properties back to immature norepinephrine stores that halt inotropic effects and longer elimination half time related to age that accentuate side effects of dopamine such as tachycardia.[3] Such side effects may accentuate in renal and hepatic deficiency because of lower clearance of dopamine and risk of toxicities in usual doses administration.[4] The other challenging factor for easy administration of dopamine is various inter individual pharmacokinetics property of dopamine especially in seriously ill patients.[5] Cochran study in small sample of selected asphyxiated neonate cases showed low dose dopamine as low as 2.5 micrograms/kg/min cannot decrease mortality and morbidity compared to placebo[6] and doses as low as 7 micrograms/kg/min make pulmonary vasoconstriction in critically ill case and infusion rate of 5 micrograms/kg/min cannot bring target hemodynamic indices in a great proportion of patients (9 of 25) inspite of tachycardia occurred in them as a side effect without increase in stroke volume and modest reduction in systemic vascular resistance.[7-8] Dopamine, efficacy, decrement during lactic acidosis is another challenge in spite of the plasma norepinephrine level was elevated dramatically during severe lactic acid acidosis in compared to normal acidosis.[9]

Les troubles du sommeil chez les patients atteints d’un trouble neurocognitif

IntroductionSleep disorders are prevalent in patients with a neurocognitive disorder, and diagnosis and treatment in these patients remain challenging in clinical practice. MethodsThis narrative review offers a systematic approach to diagnose and treat sleep disorders in neurocognitive disorders. ResultsAlzheimer's disease is often associated with circadian rhythm disorders, chronic insomnia, and sleep apnea-hypopnea syndrome. Alpha-synucleinopathies (e.g., Parkinson's disease and Lewy body dementia) are often associated with a rapid eye movement sleep behavior disorder, restless legs syndrome, chronic insomnia, and sleep apnea-hypopnea syndrome. A focused history allows to diagnose most sleep disorders. Clinicians should ensure to gather the following information in all patients with a neurocognitive disorder: (1) the presence of difficulties falling asleep or staying asleep, (2) the impact of sleep disturbances on daily functioning (fatigue, sleepiness and other daytime consequences), and (3) abnormal movements in sleep. Sleep diaries and questionnaires can assist clinicians in screening for specific sleep disorders. Polysomnography is recommended if a rapid eye movement sleep behavior disorder or a sleep apnea-hypopnea syndrome are suspected. Sleep complaints should prompt clinicians to ensure that comorbidities interfering with sleep are properly managed. The main treatment for moderate to severe obstructive sleep apnea-hypopnea syndrome remains continuous positive airway pressure, as its efficacy has been demonstrated in patients with neurocognitive disorders. Medications should also be reviewed, and time of administration should be optimized (diuretics and stimulating medications in the morning, sedating medications in the evening). Importantly, cholinesterase inhibitors (especially donepezil) may trigger insomnia. Switching to morning dosing or to an alternative drug may help. Cognitive-behavioral therapy for insomnia is indicated to treat chronic insomnia in neurocognitive disorders. False beliefs regarding sleep should be addressed with the patient and their caregiver. The sleep environment should be optimized (decrease light exposure at night, minimize noise, avoid taking vital signs, etc.). Sleep restriction can be considered as patients with a neurocognitive disorder often spend too much time in bed. The need for naps should be assessed case by case as naps may contribute to insomnia in some patients but allow others to complete their diurnal activities. Trazodone (50mg) may also be used under certain circumstances in chronic insomnia. Recent evidence does not support a role for exogenous melatonin in patients with a neucognitive disorder and insomnia. Patients in long-term care facilities are often deprived of an adequate diurnal exposure to light. Increasing daytime exposure to light may improve sleep and mood. Patients with circadian rhythm disorders can also benefit from light therapy (morning bright light therapy in case of phase delay and evening bright light therapy in case of phase advance). Rapid eye movement sleep behavior disorder can lead to violent behaviors, and the sleeping environment should be secured (e.g., mattress on the floor, remove surrounding objects). Medication exacerbating this disorder should be stopped if possible. High dose melatonin (6 to 18mg) or low dose clonazepam (0.125–0.25mg) at bedtime may be used to reduce symptoms. Melatonin is preferred in first-line as it is generally well tolerated with few side effects. Patients with restless legs syndrome should be investigated for iron deficiency. Medication decreasing dopaminergic activity should be reduced or stopped if possible. Behavioral strategies such as exercise and leg massages may be beneficial. Low-dose dopamine agonists (such as pramipexole 0.125mg two hours before bedtime) can be used to treat the condition, but a prolonged treatment may paradoxically worsen the symptoms. Alpha-2-delta calcium channel ligands can also be used while monitoring for the risk of falls. ConclusionMultiple and sustained nonpharmacological approaches are recommended for the treatment of sleep disturbances in patients with neurocognitive disorder. Pharmacological indications remain limited, and further randomized clinical trials integrating a multimodal approach are warranted to evaluate the treatment of sleep disorders in specific neurocognitive disorders.

Clinical efficacy of low-dose dopamine in the treatment of renal injury after neonatal asphyxia and evaluation of renal function improvement.

Clinical efficacy of low-dose dopamine in the treatment of renal injury after neonatal asphyxia and evaluation of renal function improvement.

Hemodynamics and renal function during administration of low dose dopamine in critically ill patients

Hemodynamics and renal function during administration of low dose dopamine in critically ill patients