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We present the case of a 13-year-old boy with a ruptured cerebral arteriovenous malformation who had rapidly progressive cardiac failure leading to death. Serial electrocardiograms, cardiac enzymes, echocardiograms, and pulmonary artery catheter data confirmed severe ventricular dysfunction related to myocardial ischemia and infarction. Cardiac dysfunction after cerebral insult is commonly described in adults with aneurysmal subarachnoid hemorrhage and has been termed "neurogenic stunned myocardium" because of its transient nature in most of patients. In children, cardiovascular dysfunction has been described in a few reports and only after traumatic brain injury. No deaths have been reported. This case report illustrates the potentially lethal consequences of cardiovascular dysfunction in children after ruptured cerebral arteriovenous malformation with subarachnoid hemorrhage. Compromised cardiac function should be considered during the early evaluation and management of these patients and supportive care instituted to limit secondary brain injury from poor perfusion.

The present study compared 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced microglial activation in 3 different groups, sham-operated (SHM) mice, adrenalectomized mice (ADX), and ADX mice administered with corticosterone (ADX + CORT), to investigate the roles of glucocorticoids on microglial activation and dopaminergic neurodegeneration. Acute MPTP treatment induced moderate tyrosine hydroxylase (TH)-immunoreactive neuronal loss in the substantia nigra (SN) of SHM mice; this neuronal loss was significantly enhanced in ADX mice, but eventually recovered following the administration of corticosterone. Consistent with neuronal findings, acute MPTP treatment induced microglial activation in the SN from 1-3 days post injection in SHM mice. Interestingly, microglial activation was further enhanced and occasionally showed a phagocytic morphology in ADX mice that showed no circulating corticosterone. Furthermore, the activated microglia was significantly suppressed by the administration of corticosterone to ADX mice. Moreover, a confocal microscopic study demonstrated that the expression of inducible nitric oxide synthase protein, exclusively colocalized with activated microglia in the SN in ADX mice, was substantially decreased by the administration of corticosterone. Thus, the present study, using in-vivo adrenalectomy for a dopaminergic neurodegeneration model, successfully demonstrated the neuroprotective effects of corticosterone by microglial inhibition.

Background: Dopamine is an inotrope effective in the short term treatment of acute heart failure - including that caused by coronary artery disease. Catecholamines however can potentiate platelet activation and pre-dispose to coronary thrombosis., Aims: Dopamine was studied for effect on agonist induced human platelet Ca mobilization, human platelet GP iib iiia receptor activation and acute coronary thrombosis in dogs. Calcium sensitive indo-1, fluorescent immunostaining and flow cytometry were used for platelet studies while coronary thrombosis was induced in anesthetized dogs via endothelial damage, arterial wall injury and critical stenosis., Results: Dopamine 10 and 10 M had no effect on the amplitude of the platelet Ca signal evoked by thrombin 0.1 U/mL. Likewise, dopamine 10 M had no effect on GP IIb IIIa activation evoked by ADP 10 M and by thrombin 0.1 U/mL. In dogs, intravenous dopamine 8 ug/Kg/min had no effect on repetitive cycles of acute coronary thrombus formation. In positive control studies, epinephrine increased platelet responsiveness and accelerated canine coronary thrombosis., Conclusion: Clinically relevant concentrations of dopamine did not amplify agonist induced human platelet Ca activation, GPiib iiia expression or experimental canine coronary thrombosis--providing a degree of reassurance concerning this versatile inotrope.

Background: Early hypotension is a common problem among preterm infants. Studies have shown conflicting data regarding the definition of hypotension, the way to treat it and the correlation to outcome., Objectives: To investigate the risk factors for developing hypotension and its relations to short- and long-term outcomes., Methods: Medical charts of all surviving very low birth weight infants were retrospectively reviewed during a 4-year period. The data of infants suffering from early hypotension and needed treatment were compared with those of a control group with 'normal' blood pressure. In addition, medical charts were reviewed for neurodevelopment outcome., Results: The study and control groups comprised 109 infants each. The mean blood pressures were 24.1 +/- 3.2 and 30.3 +/- 4.3 mm Hg in the study and control groups (p < 0.0001). No significant perinatal variables were found to predict hypotension. Bronchopulmonary dysplasia and retinopathy of prematurity were related to treated hypotension. Logistic regression analysis found that neonatal treated hypotension was related to periventricular leukomalacia, with an odds ratio of 2.61 (95% CI 1.0-7.12), p = 0.049. Intraventricular hemorrhages grades 2-4 were found to be related to lower mean blood pressure, with an odds ratio of 1.3 (95% CI 1.12-1.51), p < 0.01. Major long-term neurological disability was found by regression analysis to be related to periventricular leukomalacia and treated hypotension, with odds ratios of 63.1 (95% CI 13.3-299, p < 0.001) and 5.4 (95% CI 1.29-22.7, p = 0.01)., Conclusions: This study supports the hypothesis that early provision of antihypotensive therapy is related to intraventricular hemorrhage, periventricular leukomalacia and major neurodevelopment impairment., ((c) 2008 S. Karger AG, Basel.)

Treatment of Parkinson's disease has traditionally focused on the management of motor disability while behavioural disturbances have received less attention. Recently, impulse control disorders and aberrant repetitive behaviours have surged to clinical relevance as they occur during dopamine replacement treatment (mainly with dopamine agonists) and worsen patient and caregiver quality of life. Patients are unable to adequately estimate the negative consequences of their actions and are prone to entertain compulsive reward-seeking activities. This review aims to summarize current evidence on the epidemiology of behavioural disturbances in Parkinson's disease, recent insights into their neurobiological basis and to discuss strategies for management and prevention. Studies from 1990 through to December 2008 were retrieved via searches of the Cochrane Database of Systematic Reviews and PubMed. The mechanisms underlying the development of behavioural disturbances in Parkinson's disease are debated but current evidence points to specific risk factors: male sex, young age at onset, underlying personality traits characterized by high impulsivity and novelty seeking, and personal or family history of addictive disorders. Specifically, in predisposed individuals dopamine replacement therapy leads to overstimulation of dopamine receptors within the mesocorticolimbic pathways and in turn to the development of addictive behaviours, such as impulse control disorders and compulsive medication intake. Since these disturbances affect individuals who have often unremarkable psychiatric history and no cognitive impairment, their identification and management is complex. Compulsive medication intake (described as 'hedonistic homeostatic dysregulation' or 'dopamine dysregulation syndrome') is commonly associated with fluctuations in advanced disease, while impulse control disorders frequently occur in early Parkinson's disease and within normal-range medication dosages. Management primarily requires reduction of dopaminergic therapy but psychosocial support is often required. Use of selective serotonin reuptake inhibitors in the dose used for obsessive compulsive disorders may help, while benefit from atypical antipsychotics is limited in most cases. Deep brain stimulation should be considered with caution in these subjects. Prevention is based on the identification of at-risk individuals and active monitoring. Given the social and potentially medical-legal consequences of these behaviours, we encourage treating physicians to discuss risks with patients before treatment is initiated.

Objectives: Simultaneous pancreatic-renal transplant is an effective treatment for insulin-dependent patients with chronic renal failure. We sought to identify the main influences on pancreatic and patient survival rates after simultaneous pancreas-kidney transplants., Patients and Methods: The 1-year patient and pancreas survival rates of 150 patients who had undergone simultaneous pancreas-kidney transplant were analyzed by the Cox proportional hazards regression model and the Kaplan-Meier method. Uni and multivariate analyses were performed in terms of transplant-, recipient-, and donor-related risk factors., Results: At 1 year, patient and pancreatic allograft survival rates were 82% and 76.7%, respectively. Delayed graft function in the kidney (P = .001, HR 5.41), acute kidney rejection (P = .016, HR 3.36), and intra-abdominal infection (P < .0001, HR 4.15) were the main factors related to 1-year patient survival. Pancreatic allograft survival at 1 year was related to intra-abdominal infection (P < .0001, OR 12.83), vascular thrombosis (P = .002, OR 40.55), acute kidney rejection (P = .027, OR 3.06), donor sodium greater than 155 mEq/L (P = .02, OR 3.27), and dopamine administration exceeding 7.6 microg/kg/min (P = .046, OR 2.85)., Conclusions: Delayed kidney allograft function and intra-abdominal infection had an important effect on both patient and pancreatic allograft survival rates.

Ochronosis is a rare disease. Usually symptoms appear in the third, fourth, or later decade of life. The most common symptom is arthropathy, but cardiovascular system can be involved in this disease. A 71-year-old man with ochronosis was scheduled for total hip arthroplasty. Preoperatively, echocardiogram revealed aortic valve stenosis, mitral valve stenosis, and hypokinesis on antero-septal, lateral and posterior walls. Coronary angiogram revealed 50-75% stenosis of the left anterior descending coronary artery (segment 7) and 100% stenosis of the left circumflex artery (segment 15). Before the induction of general anesthesia, electrocardiogram showed first-degree atrioventricular block. After the induction of general anesthesia, blood pressure decreased markedly. Phenylephrine administration and rapid infusion of extracellular fluid failed to increase blood pressure. Thus, we started to administer dopamine at an infusion rate of 10 microg x kg(-1) x min(-1) which increased blood pressure effectively, but electrocardiogram showed second-degree atrioventricular block (Mobitz type II). We started rapid infusion of a plasma substitute, and gradually decreased the infusion rate of dopamine to 4 microg x kg(-1) x min(-1). Then electrocardiogram returned to first-degree atrioventricular block. We estimated that second-degree atrioventricular block in this patient might have been exaggerated by dopamine at least in part.

There is an increasing awareness that impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, can occur as a complication of Parkinson's disease (PD). In addition, other impulsive or compulsive disorders have been reported to occur, including dopamine dysregulation syndrome (DDS) and punding. Case reporting and prospective studies have reported an association between ICDs and the use of dopamine agonists (DAs), particularly at greater dosages, whereas dopamine dysregulation syndrome has been associated with greater dosages of levodopa or short-acting DAs. Data suggest that risk factors for an ICD may include male sex, younger age or younger age at PD onset, a pre-PD history of ICD symptoms, personal or family history of substance abuse or bipolar disorder, and a personality style characterized by impulsiveness. Although psychiatric medications are used clinically in the treatment of ICDs, there is no empiric evidence supporting their use in PD. Therefore, management for clinically significant ICD symptoms should consist of modifications to dopamine replacement therapy, particularly DAs, and there is emerging evidence that such management is associated with an overall improvement in ICD symptomatology. It is important that PD patients be aware that DA use may lead to the development of an ICD, and that clinicians monitor patients as part of routine clinical care. As empirically validated treatments for ICDs are emerging, it will be important to examine their efficacy and tolerability in individuals with cooccurring PD and ICDs.

Introduction: Drug-induced cardiovascular effects identified in conscious cynomolgus monkeys equipped with tethers and prepared for radiotelemetry were compared with results from anesthetized non-human primate (cynomolgus and rhesus) models., Methods: Remifentanil (4.0 microg/kg, bolus), esmolol (2.0 mg/kg, bolus) and dopamine (0.05 mg/kg/min, 30 min infusion) were given intravenously to all models., Results: Remifentanil decreased heart rate (HR), systolic, mean and diastolic systemic arterial pressures (SAP) in anesthetized animals while conscious monkeys presented an increase in HR, systolic, mean and diastolic SAP, as seen in humans for the respective state of consciousness (conscious and anesthetized). Esmolol decreased HR, systolic, mean and diastolic SAP in anesthetized monkeys while only HR, systolic and mean SAP achieved a statistically significant decrease in the conscious model. The amplitude of SAP reduction was greater in anesthetized models, while the amplitude of HR reduction was greater in the conscious and anesthetized cynomolgus models than in the anesthetized rhesus model. Dopamine induced a significant increase in HR, systolic, mean and diastolic SAP in anesthetized models without any statistically significant effect on HR and SAP in the conscious model., Discussion: The amplitude of hemodynamic and chronotropic alterations induced by positive control drugs was generally greater in anesthetized than in conscious models and statistical significance was achieved more often with the anesthetized models. These results suggest that an anesthetized model may be valuable as part of a drug screening program for cardiovascular safety evaluations in addition to a conscious model.

Hypotension is commonly encountered during carotid artery stenting (CAS), mediated by vagal stimulation and suppression of sympathetic outflow. Some patients require treatment with intravenous vasopressors (dopamine, nor-epinephrine, or phenylephrine). The authors describe the successful use of the oral agent midodrine as an alternative to intravenous vasopressors in the treatment of hypotension related to CAS. Of 55 patients who underwent elective CAS, 19 (35%) experienced significant hypotension, and 15 (27%) required vasopressor therapy. Eleven patients received intravenous dopamine infusion in an intensive care setting, whereas 4 received oral midodrine in a regular telemetry unit. All patients eventually recovered and were discharged without any residual cardiovascular or neurological complications. No major side effects were noted with the use of both dopamine and midodrine. Cost of hospitalization was significantly higher in the dopamine group because of the need for ICU admission.

Acute renal failure (ARF) in horses is usually prerenal or renal in origin and is most often caused by hemodynamic or nephrotoxic insults. The clinical management of patients that have ARF is largely supportive, including correction of fluid deficits and electrolyte and acid-base disturbances and treatment and reversal of the underlying cause. Use of dopamine and mannitol to promote renal blood flow and urine output is no longer recommended.

Aim: To investigate the effect of dopamine on retinal and choroidal blood flow in humans., Methods: We investigated the effect of two doses of intravenous dopamine (5 and 10 microg/kg/min) via a randomised double-masked crossover study in 12 healthy subjects chosen from a total of 16. Blood flow parameters in retina, optic nerve head and choroid were assessed with bi-directional laser Doppler velocimetry, laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude, respectively., Results: Intravenous dopamine dose-dependently increased retinal blood cell velocity and fundus pulsation amplitude (p<0.001). At the highest administered dose red blood cell velocity in retinal vessels increased by 37% and fundus pulsation amplitude by 24%. By contrast, optic nerve head blood flow did not change with dopamine administration., Conclusions: Our data indicate that dopamine has a pronounced enhancing effect on the retinal perfusion in humans. Further studies are required to establish the exact role of dopamine in the regulation of choroidal and optic nerve head blood flow.

Dopamine is mostly used in patients with cardiogenic or septic shock, but its place in critical care medicine is often questioned. Dopamine, of which pharmacology in children is variable, is prescribed for its inotropic effect, associated with an increase in cardiac output and at a lesser degree blood pressure. Beneficial effects (need for renal replacement therapy and mortality) of low dose in patients at risk of, or with acute renal failure are not demonstrated. Dopamine has numerous potential deleterious effects on local circulations (pulmonary, cerebral, coronary and cutaneous), respiratory function, gastroduodenal motility, endocrine function (further depression of the hypothalamic-pituitary axis induced by stress) and immunity (partially due to decreased production of prolactin). Finally, in shocked adults dopamine infusion might be associated with an increase in mortality rate. Dopamine remains the most prescribed catecholamine, either in adults or children. It still is one of the first line drug included in the recent recommendations for the treatment of septic shock (norepinephrine tends to replace it), cardiogenic shock (dobutamine is the first drug), severe head trauma, and organ donor in cerebral death. In conclusion, if dopamine is today less used, there is no proof that its deleterious effects are associated with an excess of mortality. Thus, dopamine still is part of the stock of drugs that act on the cardiocirculatory system (but for how long?).

The antagonism of melatonin in models of Parkinson's disease (PD) can reduce the severity of motor impairment associated with dopamine (DA) degeneration. In consideration of the potent antidepressant effects of bright light therapy (LT), that LT suppresses melatonin secretion, that depression is commonly observed in PD, and that exposure to constant light facilitates recovery from experimental PD, the object of the present study was to strategically administer LT to PD patients and observe the effects on depression, insomnia, and motor performance. Twelve patients diagnosed with PD were exposed to white fluorescent light for 1-1.5 h at an intensity of 1000 to 1500 lux once daily commencing 1 h prior to the usual time of sleep onset, approximately 22:00 h in most patients. All patients were assessed before LT commenced and at two weeks, five weeks, and regular intervals thereafter. Within two weeks after commencing LT, marked improvement in bradykinaesia and rigidity was observed in most patients. Tremor was not affected by LT treatment; however, agitation, dyskinaesia, and psychiatric side effects were reduced, as verified by decreased requirement for DA replacement therapy. Elevated mood, improved sleep, decreased seborrhea, reduced impotence, and increased appetite were observed after LT. LT permitted the reduction of the dose of L-dopa, bromocriptine, or deprenyl in some patients by up to 50% without loss of symptom control. Factors limiting the efficacy of LT included multiple disease states, treatment compliance, polypharmacy, emotional stress, advanced age, and predominance of positive symptoms. The results of this case series study confirms previous work describing light as efficacious in the treatment of PD and suggest that controlled trials may help to elucidate how LT might be used strategically as an adjunct therapy to improve the morbidity of PD patients.

Objectives: The purpose of this study was to evaluate the effects of dopamine on hemodynamic status and oxygen transport in neonates after the Norwood procedure., Background: Dopamine is widely used to augment cardiac performance and increase oxygen delivery (DO2) in patients after cardiopulmonary bypass (CPB). This might be at the expense of increased myocardial and systemic oxygen consumption (VO2), thus offsetting the improved DO2. This balance is particularly fragile in critically ill neonates., Methods: Systemic oxygen consumption was continuously measured with respiratory mass spectrometry in 13 sedated, paralyzed, and mechanically ventilated neonates for 72 h after the Norwood procedure. Arterial, superior vena caval, and pulmonary venous blood gases were measured to calculate pulmonary blood flow (Q(p)) and systemic blood flow (Q(s)), DO2, and oxygen extraction ratio (ERO2). Rate-pressure product was calculated. Dopamine at a dose of 5 microg/kg/min was routinely administered at cessation of CPB and terminated within the first 48 h. Hemodynamic and oxygen transport measures were obtained before and at 100 min after the termination of dopamine., Results: Terminating dopamine was not associated with significant changes in arterial pressure, Q(p), Q(s), or DO2 but was associated with a significant decrease in heart rate (p = 0.003), rate-pressure product (p = 0.03), and VO2 (-20 +/- 11%, p < 0.0001), resulting in a significant decrease in ERO2 (p = 0.01)., Conclusions: Dopamine induces a significant increase in VO2 in neonates after the Norwood procedure, and termination is associated with an improved balance of VO2-DO2. These data further emphasize the importance of understanding changes in VO2 as well as DO2 in infants after cardiac surgery.

For much of the last four decades, low-dose dopamine has been considered the drug of choice to treat and prevent renal failure in the intensive care unit (ICU). The multifactorial etiology of renal failure in the ICU and the presence of coexisting multisystem organ dysfunction make the design and execution of clinical trials to study this problem difficult. However, in the last decade, several meta-analyses and one large randomized trial have all shown a lack of benefit of low-dose dopamine in improving renal function. There are multiple reasons for this lack of efficacy. While dopamine does cause a diuretic effect, it does very little to improve mortality, creatinine clearance, or the incidence of dialysis. Evidence is also growing of its adverse effects on the immune, endocrine, and respiratory systems. It may also potentially increase mortality in sepsis. It is the opinion of the authors that the practice of using low-dose dopamine should be abandoned. Other drugs and treatment modalities need to be explored to address the serious issue of renal failure in the ICU.

This report presents the case of an adult male with aromatic L-amino acid decarboxylase deficiency who developed serious cardiac rhythm disturbances during treatment with intravenous dopamine and norepinephrine for severe hypotension. Three weeks later, he spontaneously developed atrial fibrillation while not receiving exogenous catecholamines. He died suddenly after several months. We presume cardiac arrhythmia was the most likely cause of his death. Patients with aromatic L-amino acid decarboxylase deficiency may be prone to cardiac arrhythmias at rest and also may be exceptionally sensitive to exogenous catecholamines. Therefore, close cardiac monitoring is indicated at baseline and during treatment with pressors.

Background: Early postnatal adaptation to transitional circulation in low birth weight infants frequently is associated with low blood pressure and decreased blood flow to organs. Catecholamines have been used widely as treatment, despite remarkably little empirical evidence on the effects of vasopressor/inotropic support on circulation and on clinically important outcomes in sick newborn infants., Aims: To explore the effectiveness of low/moderate-dose dopamine and epinephrine in the treatment of early systemic hypotension in low birth weight infants, evaluate the frequency of adverse drug effects, and examine neonatal clinical outcomes of patients in relation to treatment., Design/methods: Newborns of <1501-g birth weight or <32 weeks of gestational age, with a mean blood pressure lower than gestational age in the first 24 hours of life, were assigned randomly to receive dopamine (2.5, 5, 7.5, and 10 microg/kg per minute; n = 28) or epinephrine (0.125, 0.250, 0.375, and 0.5 microg/kg per minute; n = 32) at doses that were increased stepwise every 20 minutes until optimal mean blood pressure was attained and maintained (responders). If this treatment was unsuccessful (nonresponders), sequential rescue therapy was started, consisting first of the addition of the second study drug and then hydrocortisone., Outcome Measures: These included: (1) short-term changes (first 96 hours, only responders) in heart rate, mean blood pressure, acid-base status, lactate, glycemia, urine output, and fluid-carbohydrate debit; and (2) medium-term morbidity, enteral nutrition tolerance, gastrointestinal complications, severity of lung disease, patent ductus arteriosus, cerebral ultrasound diagnoses, retinopathy of prematurity, and mortality., Results: Patients enrolled in this trial did not differ in birth weight or gestational age (1008 +/- 286 g and 28.3 +/- 2.3 weeks in the dopamine group; 944 +/- 281 g and 27.7 +/- 2.4 weeks in the epinephrine group). Other main antenatal variables were also comparable. However, responders and nonresponders differed significantly with respect to the need for cardiorespiratory resuscitation at birth (3% vs 23%), Critical Risk Index for Babies score (3.8 +/- 3 vs 7 +/- 5), and premature rupture of membranes >24 hours (39.5% vs 13.6%), respectively. No differences were found in the rate of treatment failure (dopamine: 36%; epinephrine: 37%) or need for rescue therapy according to treatment allocation. Groups did not differ in age at initiation of therapy (dopamine: 5.3 +/- 3.9 hours; epinephrine: 5.2 +/- 3.3 hours), but withdrawal was significantly later in the dopamine group. For short-term changes, mean blood pressure showed a significant increase from baseline throughout the first 96 hours with no differences between groups. However, epinephrine produced a greater increase in heart rate than dopamine. After treatment began, epinephrine patients showed higher plasma lactate (first 36 hours) and lower bicarbonate and base excess (first 6 hours) and received more bicarbonate. Patients in the epinephrine group also had higher glycemia (first 24 hours) and needed insulin therapy more often. Groups did not differ in urine output or fluid-carbohydrate supply during the first 96 hours. For medium-term morbidity, there were no differences in neonatal clinical outcomes in responders. However, significant differences were found in the incidence of patent ductus arteriosus, bronchopulmonary dysplasia, need for high-frequency ventilation, occurrence of necrotizing enterocolitis, and death between responders and nonresponders., Conclusions: Low/moderate-dose epinephrine is as effective as low/moderate-dose dopamine for the treatment of hypotension in low birth weight infants, although it is associated with more transitory adverse effects.

Substantial evidence indicates that the ventral tegmental area (VTA) of the mesocorticolimbic dopaminergic (DA) system has a key role in mechanisms of opiate dependence. Although DA neurons have been studied extensively, little is known about their activity and their response to acute morphine during morphine dependence. We recorded the activity of VTA DA neurons in five groups of anesthetized rats: drug-naive (naive) rats, morphine-dependent [(MD) implanted with pellets] rats, and three groups of withdrawn rats. Withdrawals either were precipitated by naltrexone or occurred spontaneously 24 h or 15 d after pellet removal. We confirmed that acute morphine in naive rats produced a marked increase in the firing of VTA DA neurons. We also found that the basal firing rate of VTA DA neurons was markedly higher in MD than in naive rats; however, in MD rats, acute morphine failed to increase DA activity. We confirmed inhibition of VTA DA activity in MD rats in response to precipitated withdrawal; however, this inhibition resulted only in a normalization of the firing rate to that of naive animals. In rats that had spontaneous withdrawal after 24 h or 15 d, the activity of VTA DA neurons was similar to that of naive rats, and an acute injection of morphine failed to alter their activity. Our results indicate that VTA DA neurons show long-lasting tolerance to the acute effect of morphine after withdrawal. These findings show that VTA DA neural activity is unlikely to be a factor in the altered behavioral responses that occur with acute morphine or naltrexone administration after chronic opiate exposure.

'Low-dose' dopamine is frequently used in intensive care units (ICU) for its presumed renoprotective effects, but prospective and retrospective studies have so far not proven prevention or amelioration of renal injury. Data on renal perfusion following dopamine infusion are limited. In order to circumvent the problem of patient heterogeneity in the ICU setting, we used a crossover design in a prospective, double-blind randomized controlled study to investigate the effect of 'low-dose' dopamine on renal resistance indices, as determined by Doppler ultrasound. Forty patients, 10 without and 30 with acute renal failure (ARF, defined as doubling of baseline creatinine or an increase above 2 mg/dl), were included. Dopamine (2 mug/kg min) or placebo was given intravenously in alternating sequence for four subsequent periods of 60 min, starting randomly with either dopamine or placebo. Resistive (RI) and pulsatility index (PI) were closely correlated, positively related to serum creatinine values at baseline and highly reproducible during the two paired infusion periods. Dopamine reduced renal vascular resistance in patients without ARF (median RI/PI from 0.70 to 0.65/1.20 to 1.07, P<0.01) but increased resistance indices in patients with ARF (median RI/PI from 0.77 to 0.81/1.64 to 1.79, P<0.01) in the absence of effects on systemic hemodynamics. Subgroup analysis of patients with ARF revealed that dopamine induced renal vasoconstriction above 55 years (n=22) and in patients not receiving norepinephrine (n=20). In conclusion 'low-dose' dopamine can worsen renal perfusion in patients with ARF, which adds to the rationale for abandoning the routine use of 'low-dose' dopamine in critically ill patients.

Objective: To describe the possibility that dopamine infusion can prevent early diagnosis of congenital hypothyroidism., Design: Case report., Setting: Medical neonatal intensive care unit of a tertiary academic medical center., Patients: We report four preterm newborns affected by transient primary congenital hypothyroidism who showed low serum thyroxine and normal thyroid-stimulating hormone concentrations on primary screening performed during treatment with dopamine., Interventions: Thyroid reevaluation screening after dopamine discontinuation., Measurements and Main Results: Thyroid reevaluation showed elevated thyroid-stimulating hormone levels., Conclusion: We emphasize that dopamine capacity to suppress thyroid-stimulating hormone could prevent early diagnosis of congenital hypothyroidism. We suggest all newborns to be tested simultaneously for thyroid-stimulating hormone and thyroxine values at primary screening. A reevaluation of thyroid hormones after dopamine discontinuation is advisable in patients treated with dopamine.

Striatal neurons convert L-dopa to dopamine (DA) following gene transfer of aromatic L-amino acid decarboxylase (AADC) via adeno-associated virus (AAV) in parkinsonian monkeys. We investigated whether AAV-AADC could reduce or eliminate L-dopa-induced dyskinesias (LIDs) and side effects in MPTP-treated monkeys. Five monkeys were made parkinsonian by bilateral MPTP lesions. The optimal therapeutic dose of L-dopa was determined using an acute dose response regimen. After 3 weeks of chronic L-dopa treatment, AAV-AADC or control vector was bilaterally injected into the striatum. Animals were assessed for 6 months with the same L-dopa dosing as presurgery as well as chronic oral L-dopa treatment. Presurgery LID was observed at doses greater than 5 mg/kg. The AAV-AADC-treated animals displayed an average 7.3-fold decrease in the therapeutic dose of L-dopa throughout the 6-month follow-up period. Only AAV-AADC-treated monkeys were susceptible to dyskinesias even at sub-clinical doses. Immunohistochemical analysis revealed well-delineated foci of AADC within the striatum. These results suggest that high levels of focal DA were generated in response to L-dopa administration and may be responsible for the exacerbation of dyskinesias. This may be similar to focal dopaminergic activity in PD patients that developed off-drug or "runaway" dyskinesias following fetal mesencephalic grafts.

Background: Management of cerebral perfusion pressure is an important element of the treatment of traumatic brain injury. Vasopressors are accepted as a method of choice to increase mean arterial blood pressure and thus cerebral perfusion pressure in the face of rising intracranial pressure. There are, however, some unresolved issues and potential risks to this therapy., Material and Methods: This study therefore examines the effects of dopamine on physiological changes as well as on brain edema and water content that can be readily assessed by MRI/MRS in (1) a rodent model of rapidly rising intracranial pressure, caused by diffuse injury with secondary insult and (2) a model of cortical contusion., Results: Dopamine was capable of restoring cerebral perfusion pressure in the model of rapidly rising intracranial pressure. However, this was associated with only a partial restoration of cerebral blood flow. In the brain tissue two profiles of change in the apparent diffusion coefficient of water (ADCw) were seen; one in which ADCw recovered to baseline, and one in which ADCw remained persistently low. Despite that dopamine did not alter these profiles, MRI-assessed tissue water content was increased four hours after injury and dopamine increased cerebral water content in both subgroups of injury, especially in the subgroup with a persistently low ADCw (p < 0.01). In the contusion group dopamine significantly worsened the edema both in the injured and in the contralateral area of hippocampus and temporal cortex even though the ADCw values did not change, except for the contralateral hippocampus, where both water content and ADC, values rose with treatment, suggesting extracellular accumulation of water., Conclusion: The results suggest that dopamine has a double effect--while it temporarily and partially restores cerebral blood perfusion, at the same time it induces an increase in brain swelling and thus an increase in intracranial pressure in some cases. It is possible that in a subgroup of patients vasopressor treatment leads to an opposite effect several hours later. Vasopressor therapy in the clinical setting therefore should be cautiously applied.

Acute renal failure (ARF) is common in the critically ill and is associated with a high mortality rate. Its pathogenesis is not understood. Because animal models use ischemia to induce experimental ARF, there is the widespread belief that lack of blood flow is responsible for ARF. Low-dose dopamine (LDD) has been shown to increase renal blood flow in animal and in human volunteers. Thus, it has been administered to humans for almost 3 decades in the belief that it would lead to renal arterial vasodilation and increase renal blood flow (RBF). However, the etiology of ARF in critical illness is likely multifactorial, and the contribution of hypovolemia and reduced renal perfusion is unknown. Furthermore, interindividual variation in the pharmacokinetics of dopamine typically results in poor correlation between blood levels and administered dose, making accurate and reliable delivery of LDD difficult. Finally, dopamine is a proximal tubular diuretic that increases Na(+) delivery to tubular cells, thus increasing their oxygen demands. Accordingly, even if LDD were able to preferentially increase RBF, there is no guarantee that it would restore renal parenchymal oxygen homeostasis. More important, 2 meta-analyses and a large double-blind, prospective, multiple-center, randomized controlled trial have failed to demonstrate that dopamine protects the kidney in critically ill patients with ARF. Currently, there is insufficient evidence to support the use of renal-dose dopamine in the intensive care unit.

Objective: To assess the prevalence and severity of restless legs syndrome (RLS) in the general community and to investigate its potential relationship with iron metabolism and other potential risk factors., Methods: This was a cross-sectional study of a sex- and age-stratified random sample of the general population (50 to 89 years; n = 701). The diagnosis of RLS was established by face-to-face interviews; severity was graded on the RLS severity scale. Each subject underwent a thorough clinical examination and extensive laboratory testing., Results: The prevalence of RLS was 10.6% (14.2% in women, 6.6% in men); 33.8% of all patients with RLS had mild, 44.6% had moderate, and 21.6% had severe disease expression. None had been previously diagnosed or was on dopaminergic therapy. Free serum iron, transferrin, and ferritin concentrations were similar in subjects with and without RLS. However, soluble transferrin receptor (sTR) concentrations were different in subjects with and without RLS (1.48 vs 1.34 mg/L; p < 0.001). Female sex and high sTR independently predicted the risk of RLS., Conclusion: This large survey confirms the high prevalence, female preponderance, and underrecognition of restless legs syndrome in the general community. Although two-thirds of patients had moderate to severe disease, none was on current dopaminergic therapy.

Objective: "Renal dose" dopamine (rDA; 1-3 microg/kg per min) is administered to patients after cardiac surgery to preserve or improve renal function. Many of these patients develop new-onset postoperative atrial fibrillation or atrial flutter (pAF) that could be related to rDA administration. The objective of this investigation was to determine whether there was an association between rDA and new-onset pAF in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CABG)., Setting: Research hospital., Subjects: The study population consisted of 1,731 patients undergoing CABG., Interventions: CABG with and without rDA., Design: After approval by the institutional review board, a retrospective study using the Cardiothoracic Anesthesia Patient Registry was undertaken to determine the association between rDA and pAF in patients undergoing CABG. Patients with a documented history of atrial fibrillation, those who required inotrope use during or after surgery, and those having valve surgery were excluded., Measurements and Main Results: One-thousand seven-hundred thirty-one patients undergoing CABG during the period of January 1, 2000, through June 30, 2002, were the study population; of these, 15.0% (260/1,731) developed pAF. The incidence of pAF was 23.3 % (41/176) among patients who received rDA and 14.1% (219/1,555) among those who did not receive rDA. In the multivariable logistic regression model, patient age, gender, chronic obstructive pulmonary disease or asthma, and rDA were associated with pAF (p < .01). Receipt of rDA increased the odds of developing pAF by 74%, independent of the effect of other variables., Conclusions: Renal-dose dopamine is associated with a 1.74 odds ratio of pAF developing after CABG.

Background: Surveys have documented the continued popularity of low-dose dopamine to influence renal dysfunction even though few data support it and editorials and reviews have discouraged its use., Purpose: To evaluate the effects of low-dose dopamine (< or =5 microg/kg of body weight per minute) compared with placebo or no therapy in patients with or at risk for acute renal failure., Data Sources: MEDLINE (1966-January 2005), EMBASE (1980-week 5, 2005), CANCERLIT (1975-2002), CINAHL (1982-January 2005), and CENTRAL (The Cochrane Library, fourth quarter, 2004); bibliographies of retrieved publications; and additional information from 50 trials., Study Selection: Two reviewers independently selected parallel-group randomized and quasi-randomized controlled trials of low-dose dopamine versus control., Data Extraction: Study methods, clinical and renal physiologic outcomes, and adverse events (arrhythmias and myocardial, limb, and cutaneous ischemia) were extracted., Data Synthesis: 61 trials that randomly assigned 3359 patients were identified. Meta-analyses using random-effects models showed no effect of low-dose dopamine on mortality (relative risk, 0.96 [95% CI, 0.78 to 1.19]), need for renal replacement therapy (relative risk, 0.93 [CI, 0.76 to 1.15]), or adverse events (relative risk, 1.13 [CI, 0.90 to 1.41]). Low-dose dopamine increased urine output by 24% (CI, 14% to 35%) on day 1. Improvements in serum creatinine level (4% relative decrease [CI, 1% to 7%]) and measured creatinine clearance (6% relative increase [CI, 1% to 11%]) on day 1 were clinically insignificant. There were no significant changes on days 2 and 3 of therapy., Limitations: Statistically significant between-study heterogeneity in physiologic but not clinical outcomes was unexplained by prespecified hypotheses., Conclusion: Low-dose dopamine offers transient improvements in renal physiology, but no good evidence shows that it offers important clinical benefits to patients with or at risk for acute renal failure.

Background: The neuroprotective effect of xenon has been demonstrated for glutamatergic neurons. In the present study it is investigated if dopaminergic neurons, i.e. nerve-growth-factor differentiated PC-12 cells, are protected as well against hypoxia-induced cell damage in the presence of xenon., Results: Pheochromocytoma cells differentiated by addition of nerve growth factor were placed in a N2-saturated atmosphere, a treatment that induced release of dopamine, reaching a maximum after 30 min. By determining extracellular lactate dehydrogenase concentration as marker for concomitant cellular damage, a substantial increase of enzymatic activity was found for N2-treated cells. Replacement of N2 by xenon in such a hypoxic atmosphere resulted in complete protection against cellular damage and prevention of hypoxia-induced dopamine release. Intracellular buffering of Ca2+ using the Ca-chelator 1, 2-bis(2-Aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl) ester (BAPTA) reduced the neuroprotective effect of xenon indicating the essential participation of intracellular Ca2+-ions in the process of xenon-induced neuroprotection., Conclusions: The results presented demonstrate the outstanding property of xenon to protect neuron-like cells in a hypoxic situation.

To test the relative effects on serum creatinine (CRE), blood urea nitrogen (BUN), and urine output of small-dose dopamine and fenoldopam in patients undergoing liver transplantation, we randomized 43 patients to 1 of 2 continuous infusions over 48 h, starting with anesthesia induction: fenoldopam, 0.1 microg . kg(-1) . min(-1) or dopamine, 2 microg . kg(-1) . min(-1). We used predetermined hemodynamic and intravascular volume goals (intrathoracic blood volume index 800-1000 mL/m(2), extravascular lung water index <7 mL/kg) to manage patients with an algorithm for use of mannitol and furosemide to maintain urine output >1 mL . kg(-1) . h(-1). At postoperative day 3, the median CRE increase was 0.2 mg/dL (interquartile range [IQR] -0.2-0.5) with fenoldopam and 0.5 mg/dL (IQR 0.3-0.9, P = 0.004) in the dopamine group. The BUN increase was median 2 mg/dL (IQR -2-8) versus 8.5 mg/dL (IQR 5-12, P = 0.01), respectively, with fenoldopam versus dopamine. Urine output was similar; however, significantly fewer fenoldopam patients required furosemide compared with dopamine patients (median 1 [IQR 0-3] versus 3 [IQR 2-4], respectively, P = 0.003). The hemodynamic effects of dopamine and fenoldopam were similar. Compared with dopamine, in the setting of liver transplantation, fenoldopam is associated with better CRE and BUN values.

Large quantitaties of inflammatory mediators are released during the course of endotoxaemia. These mediators in turn can stimulate the sympathetic nervous system (SNS) to release catecholamines, which ultimately regulate inflammation-associated impairment in tissue perfusion, myocardial impairment and vasodilatation. Treatment of sepsis is based on surgical and/or antibiotic therapy, appropriate fluid management and application of vasoactive catecholamines. With respect to the latter, discussions on the vasopressor of choice are still ongoing. Over the past decade dopamine has been considered the 'first line' vasopressor and is frequently used to improve organ perfusion and blood pressure. However, there is a growing body of evidence that dopamine has deleterious side effects; therefore, its clinical relevance seems to be more and more questionable. Nevertheless, it has not been convincingly demonstrated that other catecholamines are superior to dopamine in this respect. Apart from its haemodynamic action, dopamine can modulate immune responses by influencing the cytokine network. This leads to inhibition of expression of adhesion molecules, inhibition of cytokine and chemokine production, inhibition of neutrophil chemotaxis and disturbed T-cell proliferation. In the present review we summarize our knowledge of the immunomodulatory effects of dopamine, with an emphasis on the mechanisms by which these effects are mediated.

Cardiogenic shock is characterized by inadequate organ and tissue perfusion, due to cardiac dysfunction, predominantly following acute myocardial infarction. Mortality rates for patients with cardiogenic shock remain high, ranging from 50-70 % despite effective therapy. Rapid diagnostics, aggressive therapeutic approach (invasive or surgical revascularisation) and pharmacological support are currently used to improve the clinical outcome and survival. In the first line commonly sympathomimetics like dopamine, dobutamine, epinephrine and norepinephrine are used for the pharmacological treatment. They have a high affinity for alpha- and beta adrenergic receptors, leading to a positive inotropic cardiac function, an increase in heart rate, oxygen enhanced demand, and an increase in vasoconstriction. However, there are also some disadvantages in the use of sympathomimetics in patients with cardiogenic shock. Clearly, metabolic acidosis due to the increased oxygen demand can be observed. Vasoconstriction induced by sympathomimetics can lead to perfusion mismatch or even deficit within the microcirculation. Additionally, in some studies which give evidence that the use of sympathomimetics can directly lead to enhanced systemic inflammatory response due to an increased IL-6 expression. However, sympathomimetics are still first line therapeutics for treatment of cardiogenic shock -- with respect to dosage and duration of treatment.

Background: Enteral nutrition has multiple benefits for critically ill patients. However, the administration of enteral nutrition to patients requiring medications for cardiovascular support is controversial secondary to concerns of altered splanchnic perfusion. The objective of this study is to evaluate the tolerance of enteral nutrition in pediatric patients receiving cardiovascular medications., Methods: This was a retrospective chart review of patients admitted to the pediatric intensive care unit at Children's Healthcare of Atlanta at Egleston in a 1-year period. Patients were eligible for the study if they received enteral nutrition during or within 24 hours of requiring continuous infusion of dopamine, dobutamine, epinephrine, norepinephrine, or neosynephrine., Results: Fifty-five admissions (52 patients) met study criteria. Patients ranged in age from 1 month to 20 years old. Although a large number (71%) of patients experienced at least 1 feeding interruption, the majority (70%) of reasons cited for stopping or slowing feedings were not related to gastrointestinal (GI) tolerance. Only 29% of patients had feedings held for perceived intolerance. Vomiting was the most often-cited reason for these interruptions. Constipation was reported in 36% of patients but cited only 4 times as a reason for feeding interruption. Four patients exhibited evidence of GI bleeding. This bleeding was considered clinically insignificant in 2 patients and appeared unrelated to enteral feedings in the others., Conclusions: This study suggests that many pediatric patients receiving cardiovascular medications tolerate enteral nutrition without adverse events. Further prospective studies are needed to determine whether enteral nutrition can consistently benefit these critically ill pediatric patients.