Administration Of Low-dose Dopamine Research Articles

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.

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.

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

Low-dose dopamine infusion increases baroreflex sensitivity by inhibition of peripheral chemoreflex

Background: Inverse relation between reflex responses from arterial baroreceptors and peripheral chemoreceptors is well described phenomenon. It is unknown whether dopamine infusion by inhibiting afferent signalling from peripheral chemoreceptors would influence baroreflex sensitivity (BRS). Methods: We performed double-blinded, crossover, randomized and placebo-controlled study on 11 healthy male volunteers (median age 26 years). During low-dose dopamine (2 mcg/kg/min) and saline infusions all subjects underwent a BRS assessment with a non-invasive, sequential method and an assessment of peripheral chemosensitivity with transient hypoxic method. Hemodynamic response to hypoxia was measured non-invasively using Nexfin monitor and expressed as slopes relating changes in systolic blood pressure (SBP) and heart rate (HR) to changes in oxygen saturation. Results: Administration of low dose dopamine was associated with a significant reduction in peripheral chemosensitivity (median: 0.16 l/min/SpO2, [IQR 0.02-0.24] vs 0.40 l/min/SpO2 [IQR 0.26-1.49], p<0.005) with concomitant increase in BRS (1.42 bpm/mmHg, [IQR 1.17-1.99] vs 1.20 bpm/mmHg, [IQR 0.85-1.37], p<0.05) compared to saline. Dopamine infusion decreased SBP and HR slopes when compared to saline (0.33 mmHg/SpO2, IQR 0.27-0.53 vs 0.61 mmHg/SpO2, IQR 0.40-1.26, p=0.07; 0.44 bpm/SpO2, IQR 0.29-0.54 vs 0.56 bpm/SpO2, IQR 0.46-0.64 vs, p=0.07 respectively). Low-dose dopamine infusion did not change SBP comparing to saline infusion. Conclusion: Low-dose dopamine infusion has a beneficial effect on baroreflex sensitivity. We hypothesize that an increase in BRS is caused by concomitant attenuation of reflex response from peripheral chemoreceptors.

Effect of low dose dopamine on early graft function in living unrelated kidney donors.

To evaluate the effect of low-dose dopamine administration on the early function of the kidney in unrelated kidney donors after transplantation. In this double-blinded clinical trial, 60 adult kidney donors and 60 recipients, younger than 50 years old, were studied. Donors and recipients were randomly divided into two groups; group 1 received dopamine 3 µ/kg/min and group 2 received similar regimen of placebo. During the first 3 days postoperatively, serum levels of urea and creatinine as well as urine output and early kidney function were compared between two groups. Serum levels of creatinine and urea and urine output during the first three days after the operation did not differ statistically significantly between two groups (P = .549, P = .306, and P = .375, respectively). Early kidney function was better significantly in group 1 (5.3 ± 3.2 versus 8.6 ± 8.0 hours; P = .048). Premedication of the kidney transplant donors with low-dose dopamine accelerates early kidney function after transplantation, but has no effect on the hemodynamic status and serum levels of creatinine and urea in the donors.

Dopamine alleviation of diaphragm contractile dysfunction and reduction of deoxyribonucleic acid damage in rats

Weaning difficulties from mechanical ventilation are associated with diaphragm fatigue and reduced respiratory muscle endurance capacity. Often the work of breathing is increased during the weaning process as a result of inspiratory resistance loading (IRL). IRL produces increased free radical formation that contributes to deoxyribonucleic acid (DNA) damage. The purpose of this study was to determine whether dopamine reduced nuclei DNA damage when the work of breathing was increased. We hypothesized that the administration of low-dose dopamine (2 microg/kg/min) during IRL decreases myonuclei DNA damage associated with free radical formation. In this in vivo study, 30 male Sprague-Dawley rats were divided into three groups: (1) the sham group receiving no IRL or no intravenous fluids, (2) IRL with administration intravenous saline, and (3) IRL with intravenous low-dose dopamine (2 microg/kg/min). All rats from the same breed and similar colonies were purchased from one laboratory facility to ensure homogeneity. The animals were anesthetized and tracheotomized, and an ultrasonic sensor was attached to the right hemidiaphragm to measure diaphragm shortening. Diaphragm fatigue was produced by IRL. Dopamine (2 microg/kg/min) was infused intravenously before and during loading. The diaphragms were excised, and myonuclei DNA damage was measured using the fluorescent dyes ethidium bromide and acridine orange and comet analyses as indices of free radical injury. In rats receiving saline, diaphragm shortening decreased by 37% after 45 minutes of IRL (P = .002) compared with baseline. In contrast, rats infused with dopamine exhibited a 31% increase in diaphragm shortening after 45 minutes of IRL (P = .037). With the use of differential dye uptake, in the saline group 59% of the nuclei were apoptotic, and 18% were necrotic. However, in the dopamine group there was significantly less apoptotic nuclei (16%, P < .001) and necrotic nuclei (7%, P = .005). Myonuclei DNA damage, measured by comet analyses, was associated with tail length and tail olive moment, which were 37% and 60% greater, respectively, in the saline group than in the dopamine group (P < .05). These data support the hypothesis that low-dose dopamine during IRL reduced myonuclei DNA damage as measured by the fluorescent dyes and comet analysis. In addition, diaphragm fatigue was prevented by the administration of dopamine during IRL.

Physiologic Impact of Low-Dose Dopamine on Renal Function in the Early Post Renal Transplant Period

Low-dose dopamine (LDD) (< or =5.0 microg/kg/min) is often used in the early postrenal transplant period for its perceived improvements in renal function parameters. However, there is little published evidence to support its use. The aim of this study was to evaluate the effects of LDD on the physiologic parameters of the transplanted kidney. With local ethics approval, 20 consecutive adult patients (age range, 27-74 years), who underwent cadaveric renal transplantation with cyclosporine immunosuppression, were randomized into two study groups, each with 10 patients. The study period was over 9 hrs on the first postoperative day. This 9-hr block was divided into three 3-hr periods. Patient group 1 received a dopamine infusion over the second 3-hr period only, and patient group 2 received a dopamine infusion over both the first and third 3-hr periods. During these periods, urine flow rate (UFR), effective renal plasma flow (ERPF), creatinine clearance (CC), and total urinary sodium excretion rate (tUNa) were measured. In both groups, there were significant (P<0.05, Wilcoxon rank sum test) increases in ERPF, UFR, CC, and tUNa during LDD infusion periods compared with periods of no LDD infusion. No changes in heart rate or mean arterial blood pressure were seen with LDD administration. LDD significantly increases ERPF, UFR, CC, and tUNa in the transplanted allograft kidney treated with cyclosporine immunosuppression in the early posttransplant period.

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

Although a large number of studies have been performed regarding the renal and hemodynamic effects of the infusion of low-dose dopamine (LDD) in severely ill patients, there is still controversy on this subject. To evaluate the effects of dopamine (2 microg/kg/min) on systemic hemodynamics (lowest mean arterial pressure, MAP, highest heart rate, HR, central venous pressure, CVP), creatinine clearance (CLcr), diuresis and fractional sodium excretion (FENa+). A non-randomized, open, prospective clinical trial. An intensive care unit in a tertiary university hospital. 22 patients with hemodynamic stability admitted to the intensive care unit. Patients were submitted to three two-hour periods: without dopamine (P1), with dopamine (P2) and without dopamine (P3). The above mentioned variables were measured during each period. CLcr was assessed based upon the formula U x V/P, where U is urinary creatinine (mg/dl), V is diuresis in ml/min and P is serum creatinine (mg/dl). FENa+ was calculated based upon the formula: urinary sodium (mEq/l) x P/plasma sodium (mEq/l) x U) x 100. Results were presented as mean and standard deviation. The Student t test was used and results were considered significant if p was less than 0.05. Twelve patients (seven males and five females) were included, with a mean age of 55.45 years. There was no significant variation in MAP, HR, CVP, CLcr or FENa+ with a dopamine dose of 2 microg/kg/min. On the other hand, diuresis significantly increased during P2, from 225.4 to 333.9 ml. Infusion of 2 microg/kg/min of dopamine for 2 hours increases diuresis. At the doses studied, dopamine does not induce significant alterations in MAP, HR, CVP, CLcr and FENa+.

Bad Medicine: Low-Dose Dopamine in the ICU

Low-dose dopamine administration (ie, doses < 5 microg/kg/min) has been advocated for 30 years as therapy in oliguric patients on the basis of its action on dopaminergic renal receptors. Recently, a large, multicenter, randomized, controlled trial has demonstrated that low-dose dopamine administered to critically ill patients who are at risk of renal failure does not confer clinically significant protection from renal dysfunction. In this review, we present the best evidence and summarize the effects of low-dose dopamine infusion in critically ill patients. We review the history and physiology of low-dose dopamine administration and discuss the reasons why dopamine is not clinically effective in the critically ill. In addition to the lack of renal efficacy, we present evidence that low-dose dopamine administration worsens splanchnic oxygenation, impairs GI function, impairs the endocrine and immunologic systems, and blunts ventilatory drive. We conclude that there is no justification for the use of low-dose dopamine administration in the critically ill.

Changes in Renal Blood Flow and Real-time Renal Cortical Perfusion According to Low-dose Nitroglycerin and Dopamine Administration Following the Occlusion and Reperfusion of Liver Blood Flow in Experimental Dogs

Background: Pringle maneuver and nitroglycerin (NTG) administration to educe hemorrhage during hepatectomy may affect renal blood flow (RBF) am renal cortical perfusion (RCP) by reducing blood pressure (BP), perload and others. However, so far there have been no studies on REF and RCP changes during and after hepatic vascular maneuver in hepatectomy. The purpose of this study was to evaluate the changes in RBF and RCP along with low dose (2/kg/min) NTG with or without low dose (3/kg/min) dopamine after the occlusion and reperfusion of hepatic blood flow. Methods: Eighteen mongrel dogs were divided into three groups according to drug administration after hepatic reperfusion; control group (group C, n = 6), NTG group (group N, n = 6), and NTG with dopamine group (group N-D, n = 6). After femoral arterial and central venous catheterization, a midline abdominal incision was made, and the hepatic artery (HA) and th portal vein (PV) were exposed for clamping and declamping. Thereafter, the right renal artery was exposed, and a doppler probe for measuring RBF was placed around the right renal artery, and a thermal diffusion microprobe was inserted in the renal outer cortex to measure RCP. Hemodynamics, RBF and RCP, were repeatedly measured before and after HA and PV reperfusion. Results: No significant change in heart rate was observed in any group. The BP decreased in all the groups after HA and PV occlusion. In group C, the BP recovered to the baseline level after hepatic reperfusion but not in groups N and N-D. The RBF and RCP decreased in all groups after HA and PV occlusion. The RBF increased compared to baseline in N-D after hepatic reperfusion, and the RCP increased versus baseline in N-D, 10 minutes after hepatic repefusion. Conclusions: In conclusion, it was observed that the RBF and RCP increased compared to baseline by administering dopamine during HA and PV reperfusion. Therefore, the prophylactic administration of low dose dopamine during hepatectomy offers an effective method of protecting renal function.

Use of dopamine in acute renal failure: a meta-analysis.

To determine whether low-dose dopamine administration reduces the incidence or severity of acute renal failure, need for dialysis, or mortality in patients with critical illness. We performed a MEDLINE search of literature published from 1966 to 2000 for studies addressing the use of dopamine in the prevention and/or treatment of renal dysfunction. Data were abstracted regarding design characteristics, population, intervention, and outcomes. Results of individual randomized clinical trials were pooled using a fixed effects model and a Mantel-Haenszel weighted chi-square analysis. We identified a total of 58 studies (n = 2149). Of these, outcome data were reported in 24 studies (n = 1019) and 17 of these were randomized clinical trials (n = 854). Dopamine did not prevent mortality, (relative risk, 0.90 [0.44-1.83]; p =.92), onset of acute renal failure (relative risk, 0.81 [0.55-1.19]; p =.34), or need for dialysis, (relative risk, 0.83 [0.55-1.24]; p =.42). There was sufficient statistical power to exclude any large (>50%) effect of dopamine on the risk of acute renal failure or need for dialysis. The use of low-dose dopamine for the treatment or prevention of acute renal failure cannot be justified on the basis of available evidence and should be eliminated from routine clinical use.

Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial

Low-dose dopamine is commonly administered to critically ill patients in the belief that it reduces the risk of renal failure by increasing renal blood flow. However, these effects have not been established in a large randomised controlled trial, and use of dopamine remains controversial. We have done a multicentre, randomised, double-blind, placebo-controlled study of low-dose dopamine in patients with at least two criteria for the systemic inflammatory response syndrome and clinical evidence of early renal dysfunction (oliguria or increase in serum creatinine concentration). 328 patients admitted to 23 participating intensive-care units (ICUs) were randomly assigned a continuous intravenous infusion of low-dose dopamine (2 microg kg(-1) min(-1)) or placebo administered through a central venous catheter while in the ICU. The primary endpoint was the peak serum creatinine concentration during the infusion. Analyses excluded four patients with major protocol violations. The groups assigned dopamine (n=161) and placebo (n=163) were similar in terms of baseline characteristics, renal function, and duration of trial infusion. There was no difference between the dopamine and placebo groups in peak serum creatinine concentration during treatment (245 [SD 144] vs 249 [147] micromol/L; p=0.93), in the increase from baseline to highest value during treatment (62 [107] vs 66 [108] micromol/L; p=0.82), or in the numbers of patients whose serum creatinine concentration exceeded 300 micromol/L (56 vs 56; p=0.92) or who required renal replacement therapy (35 vs 40; p=0.55). Durations of ICU stay (13 [14] vs 14 [15] days; p=0.67) and of hospital stay (29 [27] vs 33 [39] days; p=0.29) were also similar. There were 69 deaths in the dopamine group and 66 in the placebo group. Administration of low-dose dopamine by continuous intravenous infusion to critically ill patients at risk of renal failure does not confer clinically significant protection from renal dysfunction.

Low dosage dopamine improves kidney function: current status of knowledge and evaluation of a controversial topic

The ability of low dose dopamine (1-3 micrograms x kg-1 x min-1) to cause selective renal vasodilation, to increase glomerular filtration rate, urine output, and natriuresis, is intuitively considered favourable. Dopamine, therefore, continues to be used in critically ill patients to preserve or improve renal function. Despite its application in a wide variety of disease states and in patients at risk of acute renal failure or with already decreased renal function, there is no conclusive evidence that "renal doses" of dopamine prevented acute renal failure or had any positive effect on patient outcome although it increased urine output and natriuresis consistently. Data from many clinical studies, however, are difficult to interpret due to small numbers of patients, the absence of control groups, the inability to exclude changes in cardiac output or to separate a diuretic effect of dopamine in the tubulus system from specific increases of glomerular filtration rate, and because of the variability of methods to determine renal performance (i.e. creatinine clearance, urine output, natriuresis, fractional excretion of sodium). Moreover, the routine use of dopamine is not innovous, since it may worsen gut ischaemia and suppress certain hormonal systems. Those who believe in the clinical benefits of "renal dose" dopamine argue that, even in the absence of an improvement in renal function, the maintenance of urine output could be useful in patients unresponsive to diuretics. Again, the clinical benefit of this diuretic action still needs to be shown. In conclusion, there is little justification for the routine administration of low-dose dopamine in patients at risk of renal failure. Large controlled clinical studies are urgently needed to determine whether dopamine improves renal function or prevents acute renal failure in patients at risk.

Is the Administration of Dopamine Associated with Adverse or Favorable Outcomes in Acute Renal Failure?

To explore the relationship between the administration of low-dose dopamine and outcomes in acute renal failure. Two hundred and fifty-six patients with acute renal failure randomized to the placebo arm of a multicenter intervention trial were examined. Independent correlates of low-dose (arbitrarily defined as < 3 micrograms/kg/min) and high-dose (arbitrarily defined as > or = 3 micrograms/kg/min) dopamine administration were identified. The relative risks of death, and the combined outcome of death or dialysis, were estimated using proportional hazards regression with and without adjustment for potential confounding and bias. There were 93 (36%) deaths documented; an additional 52 (20%) patients who survived required dialysis during the 60-day study period. The relative risk (RR) of death associated with the administration of low-dose dopamine was 1.11 (95% confidence interval [95% Cl] 0.66 to 1.89). The RR of death was modestly but not significantly reduced, after adjustment for the probability of treatment assignment and for relevant covariates (RR 0.82, 95% Cl 0.42 to 1.60). The RR of death or dialysis associated with the administration of low-dose dopamine was 1.10 (95% Cl 0.71 to 1.71). The RR of death or dialysis was attenuated by adjustment, but not significantly (RR 0.95, 95% Cl 0.58 to 1.58). There is insufficient evidence that the administration of low-dose dopamine improves survival or obviates the need for dialysis in persons with acute renal failure. The routine use of low-dose dopamine should be discouraged until a prospective, randomized, placebo-controlled trial establishes its safety and efficacy.

Dopexamine: studies in the general intensive care unit and after liver transplantation

1. It has been suggested that the use of dopaminergic agents in the critically ill patient may reduce the incidence of renal failure and hence mortality. 2. Dopexamine hydrochloride is a new synthetic catecholamine. Like dopamine, it stimulates dopaminergic receptors. It also stimulates beta 2-adrenoceptors. Unlike dopamine, dopexamine has minimal effect at beta 1-adrenoceptors and no alpha-adrenoceptor activity. 3. Stimulation of renal dopaminergic and beta 2-adrenoceptors independently results in dilation of the renal vasculature. A natriuresis and diuresis is also promoted by dopaminergic stimulation. 4. A comparison between the administration of low dose dopamine and dopexamine in patients undergoing orthotopic liver transplantation resulted in less renal impairment and failure in the dopexamine group, although this did not achieve statistical significance. 5. Dopexamine elimination is reduced in the absence of hepatic function. 6. A patient with terminal liver failure was treated with dopexamine and although oxygen delivery was unchanged, oxygen consumption doubled. This suggests that dopexamine affects other organs as well as the kidneys.

The prevention of renal impairment in patients undergoing orthotopic liver grafting by infusion of low dose dopamine.

Administration of low dose dopamine (2.0 micrograms/kg/minute) begun before surgery in patients undergoing liver transplantation decreases the incidence of postoperative renal impairment. Thirty-four consecutive patients in the Cambridge/King's College Hospital liver transplantation series were studied. Nineteen patients (21 transplant operations) received prophylactic low dose dopamine throughout the operative and early postoperative period, while 15 patients (15 transplant operations) received dopamine only when clinically indicated for incipient renal failure or as an inotropic agent. In the prophylactic dopamine group, only two transplant operations (9.5%) were complicated by renal impairment, whereas in the other group, 10 patients (67%) developed renal impairment (p = 0.001); of these, four developed acute renal failure (27%). Comparison of seven pairs of patients, matched for age, sex, diagnosis, operative blood loss and operative hypotension (one group receiving dopamine, the other not), revealed a significantly higher urine output in the first 24 hours and creatinine clearance 24-48 hours after surgery (p less than 0.05) in those treated prophylactically. In view of these findings, we would recommend that consideration be given to the prophylactic use of dopamine in patients undergoing orthotopic liver transplantation.

Effect of haloperidol on dopamine-induced increase in renal blood flow.

Increasing renal blood flow (RBF) by the administration of low-dose dopamine is one mechanism to increase urine output in oliguric patients. This response is mediated in part by stimulation of dopaminergic receptors in the kidney, which could be attenuated by the dopamine blocker haloperidol. We evaluated this interaction by administering both drugs in clinically used doses to six anesthetized mongrel dogs. A dopamine regimen of 2.5 micrograms/kg/min significantly increased RBF along with cardiac output and stroke volume. Simultaneous administration of haloperidol 50 micrograms/kg iv did not influence the ability of low-dose dopamine to increase RBF. Although haloperidol is an antagonist of dopaminergic receptors, the increase in RBF associated with low-dose dopamine is maintained when intravenous haloperidol is concurrently administered to dogs.