'Low-dose' dopamine worsens renal perfusion in patients with acute renal failure

'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.     

The variable effect of PEEP in acute respiratory failure associated with multiple trauma.

Both short and longterm effects of positive end-expiratory pressure (PEEP) on oxygenating capacity (OC) were investigated in three groups of patients with acute respiratory failure following multiple trauma (MT). Group A consisted of six patients with "uncomplicated" MT; Group B, eight patients with MT and generalized sepsis; Group C, nine patients with MT and lung contusion. OC was evaluated in terms of PaO2/FIO2 and P(A-a)DO2 on FIO 2 = 1.0. OC was markedly and equally reduced in the three patient groups before use of PEEP. The use of a mean PEEP of 6-7 cm H2O resulted in an initial improvement in mean PaO2/FIO2 of 152.5, 36.1, and 59.2 mm Hg, and an overall improvement of 196.8, 57.5, and 107.0 mm Hg in Groups A, B, and C, respectively. There was a similar improvement in both the initial and the overall effect of PEEP on P(A-a)DO2 in the three groups. The difference in the improvement in OC due to PEEP was statistically significant between Groups A and B. It is concluded that acute respiratory failure following MT includes a wide spectrum of clinical syndromes, and that the improvement in OCT due to PEEP depends on the clinical sydrome that is responsible for the respiratory failure associated with MT.     

Leptospiral acute renal failure: effects of dopamine and furosemide

From unpublished experience of clinicians in the rural tropics, the combination of furosemide and dopamine is beneficial in the management of mild acute renal failure in tropical disease. We studied two groups of patients with leptospirosis and mild acute renal failure whose serum creatinine ranged from 2.4 to 5 mg/dL and fractional excretion of sodium varied from 1.21 to 2.08%. Group 1, consisting of 9 patients with the serum creatinine ranging from 2.4 to 5 mg/dL, served as the control. They received only penicillin G sodium and supportive treatment. Group 2, consisting of 8 patients with the serum creatinine ranging from 2.8 to 5 mg/dL, received, in addition to penicillin, dopamine (renal dose) and furosemide along with fluid and electrolyte replacement. The control group ran the usual clinical course of acute renal failure, and 3 patients required dialysis. There was profuse diuresis, and the recovery of renal function was faster in group 2 patients. Dopamine and furosemide are therefore useful in mild acute renal failure in leptospirosis. It is felt that this combination could be beneficial in the management of mild acute ischemic renal failure due to a clean single insult.     

No early respiratory benefit with CVVHDF in patients with acute renal failure and acute lung injury.

BACKGROUND: There is debate as to whether, in patients with acute lung injury, continuous renal replacement therapy has beneficial effects on pulmonary gas exchange by mechanisms other than fluid removal. Because continuous renal replacement therapy is associated with potential morbidity and mortality, it seems unethical to perform a randomized trial in patients with acute lung injury without renal failure. Therefore, the effects of continuous venovenous haemodiafiltration with zero volume balance on gas exchange were evaluated in patients with acute renal failure and acute lung injury. Because haemofilter conditions should be comparable between patients, we opted for an evaluation of the effects during a 24-h period. Results of this trial can guide future studies in non-renal patients with acute lung injury. METHODS: In all 37 patients with acute renal failure and acute lung injury, treated with continuous venovenous haemodiafiltration with zero fluid balance during a 1 year period, ventilatory and haemodynamic parameters were measured every 8 h during the 24 h preceding therapy and during the first 24 h of therapy. RESULTS: We found a slight, although not statistically significant, increase in the PaO(2)/FIO(2) ratio and the oxygenation index, in the total group of patients, and in the subgroups of patients with acute lung injury of extrapulmonary and pulmonary causes. CONCLUSIONS: During the first 24 h of treatment, continuous venovenous haemodiafiltration with zero volume balance did not result in a significant improvement of the respiratory status in patients with acute renal failure and acute lung injury, nor in the subgroups of patients with acute lung injury with extrapulmonary causes.     

Furosemide and dopamine in malarial acute renal failure

The effects of furosemide and furosemide with dopamine on renal function were studied in 23 patients with acute renal failure due to falciparum malaria whose serum creatinine ranged from 230 to 947 mumol/l. Furosemide given intravenously at the dosage of 200 mg 6 hourly for a period of 4 days did not alter the clinical course of renal failure. Intravenous administration of furosemide (200 mg 6 hourly) with dopamine (1 microgram/kg/min) for 4 days increased creatinine clearance and arrested the progress of renal failure when the serum creatinine was less than 400 mumol/l, but failed to alter the course of renal failure when the serum creatinine exceeded 600 mumol/l.     

Role of serotonin in patients with acute respiratory failure.

An early event in the evolution of acute respiratory failure (ARF) is thought to be the activation of platelets, their pulmonary entrapment and subsequent release of the smooth muscle constrictor serotonin (5HT). This study tests the thesis that inhibition of 5HT will improve lung function. The etiology of ARF in the 18 study patients was sepsis (N = 10), aspiration (N = 3), pancreatitis (N = 1), embolism (N = 2), and abdominal aortic aneurysm surgery (N = 2). Patients were divided into two groups determined by whether their period of endotracheal intubation was less than or equal to 4 days (early ARF, N = 12) or greater than 4 days (late ARF, N = 6). Transpulmonary platelet counts in the early group showed entrapment of 26,300 +/- 5900 platelets/mm3 in contrast to the late group where there was no entrapment (p less than 0.05). The platelet 5HT levels in the early group were 55 +/- 5 ng/10(9) platelets, values lower than 95 +/- 15 ng/10(9) platelets in the late ARF group (p less than 0.05), and 290 +/- 70 ng/10(9) platelets in normals. The selective 5HT receptor antagonist, ketanserin was given as an intravenous bolus over 3 minutes in a dose of 0.1 mg/kg, followed by a 30-minute infusion of 0.08 mg/kg. During this period mean arterial pressure (MAP) fell from 87 +/- 5 to 74 +/- 6 mmHg (mean +/- SEM) (p less than 0.05). One and one-half hours following the start of therapy, MAP returned to baseline. At this time, patients with early ARF showed decreases in: physiologic shunt (Qs/QT) from 26 +/- 3 to 19 +/- 3 (p less than 0.05); peak inspiratory pressure from 35 +/- 2 to 32 +/- 2 cmH2O (p less than 0.05) and in mean pulmonary arterial pressure from 32 +/- 2 to 29 +/- 1 mmHg (p less than 0.05). At 4 hours all changes returned to baseline levels. In early ARF ketanserin did not alter pretreatment values of: pulmonary arterial wedge pressure, 17 +/- 3 mmHg; cardiac index, 2.8 +/- 0.3 L/min X m2; platelet count, 219,000 +/- 45,000/mm3; platelet 5HT, 55 +/- 5 ng/10(9) platelets; plasma 5HT, 142 +/- 21 ng/ml; plasma thromboxane B2, 190 +/- 30 pg/ml; or plasma 6-keto-PGF1 alpha, 40 +/- 10 pg/ml. Ketanserin infusion in patients with late ARF yielded no benefit. In both ARF groups the decreases in QS/QT were inversely related to the duration of intubation (r = 0.70; p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

Branched-chain amino acid in chronic renal failure patients: respiratory and sleep effects.

Sleep disorders, including a high incidence of sleep apnea, have been recognized as a significant problem in chronic renal failure (CRF) patients. In a preliminary study, we examined CRF patients on maintenance hemodialysis for three nights; one control night, and thereafter randomized to infusion of saline (placebo) for one night and 4% branch-chain amino acid (BCAA) solution for one night. Polysomnographic and respiratory data [respiratory rate, oxygen saturation and end-tidal CO2 (ETCO2)] was recorded continuously throughout the nights and data from each hour compared with baseline (awake) values. The patients studied were characterized by reduced sleep quality and decreased amount of rapid eye movement (REM) sleep. The BCAA infusion was associated with a return of REM sleep to normal and a significant decrease in ETCO2 during both REM and non-REM sleep (P less than 0.05). Our findings demonstrate respiratory stimulation during sleep with infusion of BCAA; this stimulatory effect on respiration (in contrast to many respiratory stimulants) is associated with an increased amount of REM sleep.     

Fenoldopam prophylaxis of postoperative acute renal failure in high-risk cardiac surgery patients

Background

Acute renal failure requiring replacement therapy occurs in 1% to 2% of patients who have undergone cardiac surgery with cardiopulmonary bypass and is associated with a very high mortality rate. The aim of this study was to determine if prophylactic treatment with fenoldopam mesylate of patients at high risk of postoperative acute renal failure reduced the incidence of this event.

Methods

This was a multicenter, prospective, cohort study in which 108 patients at high risk of postoperative acute renal failure and undergoing cardiac surgery with cardiopulmonary bypass were treated with fenoldopam mesylate (0.08 μg · kg⁻¹ · min⁻¹) starting at the induction of anesthesia and throughout at least the next 24 hours. A homogeneous control group of 108 patients was created using a propensity-score analysis.

Results

Fenoldopam prophylaxis was significantly associated with a reduction in acute renal failure incidence (from 22% to 11%, p = 0.028), a less pronounced creatinine clearance decrease (p = 0.05), and a lower mortality rate (6.5% versus 15.7%, p = 0.03) by the univariate analysis, but these results were not confirmed by a multivariable analysis. Within the subgroup of patients who suffered a postoperative low output syndrome, fenoldopam prophylaxis was an independent protective factor for postoperative renal failure (odds ratio, 0.14; 95% confidence interval, 0.03 to 0.7; p = 0.017).

Conclusions

Given the limitations of a nonrandomized prospective trial, our results support the hypothesis that fenoldopam may reduce the risk of acute renal failure in patients in whom endogenous and exogenous cathecolamines action may induce a renal vascular constrictive condition.     

Predictors of acute renal failure requiring renal replacement therapy post cardiac surgery in patients with preoperatively normal renal function

Acute renal failure requiring continuous renal replacement therapy post cardiac surgery carries a high mortality. Most studies have focused on patients with impaired renal function preoperatively but little is known about predictors of such a complication in patients with preoperatively normal renal function. This is a retrospective review of a prospective collected database. A total of 1609 patients underwent cardiac surgery over a 4-year period. Dialysis was required in 47 patients (2.9%). Univariate analysis identified the following as significant risk factors: age, female gender, chronic obstructive pulmonary disease, congestive cardiac failure, creatinine clearance, Euro, Parsonnet and Cleveland clinic scores, body mass index, non-isolated CABG, cardiopulmonary bypass time, extubation time and pulmonary complications (P<0.05). Multivariate analysis identified EuroSCORE, congestive cardiac failure, insulin-dependent diabetes, emergency surgery, postoperative extubation time and pulmonary complications as independent risk factors (P<0.05). In-hospital mortality and length of stay (P<0.0001) were higher in dialysis group. Acute renal failure requiring dialysis post cardiac surgery is associated with a higher mortality and prolonged hospital stay. By identifying higher risk patients, early planned preventative measures should be readily available to both reduce the incidence of such a complication and improve utilisation of hospital resources.     

Improving the prognosis in acute renal and respiratory failure

We have achieved smooth homeostasis in patients with acute renal and respiratory failure by means of machine-controlled, continuous ultrafiltration and simultaneous bicarbonate hemodialysis with a polysulfone, biocompatible membrane (CUPID). No adverse effects were seen, even after 22 days of continued treatment. Mortality was reduced (7/14) when compared to that of a similar group given short conventional daily acetate hemodialysis and ultrafiltration with a cuprophane membrane (12/18).     

Exercise-induced acute renal failure in 3 patients with renal hypouricemia

Three cases of exercise-induced non-oliguric acute renal failure in patients with renal hypouricemia, an isolated defect of the renal urate transport system, are described. During acute renal failure, the serum uric acid levels were 5.6, 2.7 and 5.8 mg/dl, respectively, and were within normal limits. The values representing the fractional excretion of uric acid (FEUA) were 28.7, 60.0 and 12.7%, with accompanying serum creatinine levels of 8.1, 3.9 and 3.3 mg/dl, respectively. After recovery, the serum uric acid fell to 0.6, 0.7 and 1.0 mg/dl and the FEUA increased to 79.3, 52.8 and 43.2%, respectively. Two of the patients examined exhibited decreased reabsorption of filtered urate. These 3 examples of renal hypouricemia represented 23% of 13 cases of mild exercise-induced acute renal failure encountered within our experience.     

Dialysis adequacy in patients with acute renal failure

Measurement of dialysis adequacy in patients with end-stage renal disease involves the use of urea kinetic modeling, which is a reflection of both dietary protein intake and efficiency of small solute clearance. Different dialytic modalities are available for patients in acute renal failure, including intermittent hemodialysis, continuous renal replacement therapies and peritoneal dialysis. In recent years, there has been a growing effort to measure dialysis adequacy in patients with acute renal failure using urea kinetic modeling. This initiative has been driven by the persistently high mortality rates in patients with dialysis-requiring acute renal failure, which may partly be related to inadequate dialysis dosing. In the setting of acute renal failure, dialysis adequacy has been measured using both single-pool and double-pool urea kinetics, as well as blood-based and dialysate-based urea kinetic modeling. Unfortunately, current goals and methods of measuring dialysis adequacy have been extrapolated from the end-stage renal disease patient population. These extrapolations are problematic because of differences in total body water, protein catabolic rate, and vascular access. Continuous renal replacement therapy has theoretical advantages over intermittent hemodialysis, including a decreased tendency to induce hypotension, and improved solute clearance and fluid removal, while allowing intensive nutritional support, and a better clearance of medium- to large-size molecules. The latter may play a significant role in patients with sepsis-associated acute renal failure. To date, comparative studies are scant and equivocal in establishing the superiority of a particular dialysis dose or modality.     

Thyroid function in patients with acute renal failure

Thyroid function was evaluated in a group of 36 patients with acute renal failure (ARF) during the oliguric/anuric, polyuric and postpolyuric phase. Serum thyroxine (T₄) and triiodothyronine (T₃) concentrations were significantly decreased in the oliguric/anuric phase, as compared with the mean values obtained in the postpolyuric phase and with controls.In contrast to T₃ and T₄, the concentration of serum reverse triiodothyronine (rT₃) was elevated in the oliguric/anuric phase and normal in the polyuric phase. The sephadex-T₃-binding index (T₃I) was significantly increased in oliguric/anuric patients and in the polyuric phase. The levels of serum thyreotropin were significantly elevated during all phases of ARF as compared with the controls. From the results obtained it is concluded that abnormal peripheral metabolism of T₄ seems to be the primary cause of altered plasma concentrations of thyroid hormones in patients with ARF.