Alan Henderson

Effect of postoperative low-dose dopamine on renal function after elective major vascular surgery.

Prolonged aortic cross-clamping, hypotension, and large-volume blood transfusions are important risk factors in the development of postoperative renal failure after major vascular surgery [1-3]. Acute renal failure carries a high mortality rate, and its avoidance remains an important goal of postoperative management [1-3]. Dopamine (an endogenous catecholamine) has, since the pioneering work of Goldberg, been used in intensive care units to treat patients with renal impairment and to preserve renal function in patients at risk for renal failure. At low doses (0.5 to 3.0 g/kg per minute), dopamine stimulates type 1 and type 2 dopamine receptors [4, 5]. These receptors are widely distributed on the renal vasculature and, when stimulated, produce renal vasodilatation, increased renal blood flow, and increased glomerular filtration with natriuresis and diuresis [6]. These responses are most pronounced in euvolemic patients. In hypovolemic patients, a dopamine-induced diuresis may worsen the hypovolemia. Although low-dose dopamine is widely used in intensive care units as a renal protector in patients at risk for renal impairment, no evidence exists that it decreases the incidence of renal failure or mortality [7-9]. In dogs and humans, dopamine is ineffective as a renal protective agent [10, 11]. In liver transplant recipients, the evidence is conflicting. Early work by Polson and colleagues [9] claimed improved renal function with dopamine, but a more recent study showed no benefit [12]. In view of the uncertainty about the efficacy of routine low-dose dopamine as a renal protective agent, we did a study to assess the effect of low-dose dopamine on renal function in euvolemic patients after major elective vascular surgery. Methods After receiving approval from the ethics committee of Princess Alexandra Hospital, informed consent was obtained for this study from 37 consecutive patients presenting to the vascular surgical unit (during a 7-month period) for elective infrarenal abdominal aortic aneurysm repair or aortobifemoral grafting. The vascular surgical service is 1 of 3 major public vascular units serving about 1 million persons in the Brisbane area. On the day before surgery, plasma urea and creatinine levels were assayed. Creatinine clearance was measured using an accurately timed 2-hour collection [13]. The anesthetic technique was similar for all patients and included an opioid-local anesthetic epidural for postoperative analgesia. The hospital pharmacy randomly assigned dopamine and an equal volume of saline to identical containers using a random numbers table. The containers were identified only by a number (numbers 1 to 40), and the contents were unknown to the staff and the patients of the intensive care unit. All patients were admitted to the intensive care unit postoperatively and were started on an infusion of either dopamine (3 g/kg per minute) for 24 hours or placebo (saline), which was chosen in a double-blind manner by selecting the next number in the sequence 1 to 40. The management in the intensive care unit was otherwise usual for both groups; it included an infusion of Plasmalyte 56 (Baxter Health Care; Old Toongabbie, New South Wales, Australia), 3000 mL during 24 hours, and included bolus infusions of Plasmalyte 148 (Baxter Health Care) to maintain a urine flow of 1 to 1.5 mL/kg per hour. Mannitol and diuretic agents were not used. Postoperative fluid requirement and urine output during the first 24 hours in the intensive care unit were recorded. Plasma creatinine levels, serum urea levels, and creatinine clearance were measured at 24 hours and 5 days. Urine output and fluid requirements were indexed to body weight, whereas clearance values were indexed to the body surface area. All biochemical measurements were made using a SMAC II Autoanalyzer (Technicon Equipment, Sydney, Australia). Statistical analysis was done using SPS-PC software (SPS Australasia, Crows Nest, New South Wales, Australia), with the data presented as means and 95% confidence intervals (CIs). Results Eighteen patients received dopamine, and 19 patients received placebo. One patient from the placebo group and 3 from the dopamine group had myocardial infarctions. Two patients died during the study and both were in the dopamine group (1 patient, myocardial infarction; 1 patient, renal failure). These patients were included in the 24-hour analysis but were excluded from the 5-day analysis. The groups were similar with respect to age, preoperative morbidity, diuretic use, radionucleotide ejection fraction, urea creatinine levels, type of surgery, duration of aortic cross-clamping, and blood loss (Tables 1 and 2). The mean fluid requirements in the first 24 hours were slightly less in the dopamine group than in the placebo group (4.06 mL/kg per hour for dopamine compared with 5.29 mL/kg per hour for placebo, a difference of 1.23 [95% CI, 0.11 to 2.57]), whereas the mean urine volumes were slightly higher in the dopamine group (1.83 mL/kg per hour for dopamine compared with 1.6 mL/kg per hour for placebo, a difference of 0.23 [CI, 0.18 to 0.64]). Table 1. Patient Characteristics by Treatment Group* Table 2. Differences in Renal Function for Dopamine Compared with Placebo at Different Time Points Table 2 summarizes the differences between the groups in plasma creatinine levels, urea levels, and crude and indexed creatinine clearance; all variables were measured preoperatively and postoperatively (at 24 hours and 5 days). Table 3 summarizes the mean change in each variable from the preoperative level to the 24-hour and 5-day point in the dopamine and placebo groups. There was no statistical difference in plasma creatinine levels between groups at any of the time periods or in changes from baseline to 24 hours and 5 days. Table 3. Postoperative Renal Indices Compared with Preoperative Indices* Preoperative and 5-day plasma urea levels were not statistically different between groups. At 24 hours, a small decrease in urea levels was noted in both groups (5.71 mmol/L for dopamine compared with 4.99 mmol/L for placebo, a difference of 0.72 [CI, 0.62 to 2.06; P > 0.2]). The mean decrease in urea levels from baseline to 24 hours was small in both groups ( 1.07 mmol/L for dopamine compared with 1.84 mmol/L for placebo, a difference of 0.77 [CI, 0.12 to 1.67; P = 0.09]). The preoperative creatinine clearance in the placebo group was 18% lower than in the dopamine group (P = 0.16) (Table 2). By 24 hours, the creatinine clearance increased by 0.165 mL/s (9.89 mL/min) in the dopamine group and by 0.199 mL/s (11.98 mL/min) in the placebo group (P > 0.2). By day 5, the creatinine clearance in the dopamine group had decreased to near baseline, although the increase was sustained in the placebo group. However, the difference between the group means was 0.28 mL/s ( 0.103 mL/s compared with 0.178 mL/s [CI, 0.2 to 0.21; P > 0.2]). Indexing creatinine clearance for body surface area did not change the interrelation of the major end points in either group. Discussion In this study, minor changes in renal function were noted postoperatively in the placebo and dopamine groups. In both groups, a small decrease was noted in plasma urea levels and a small increase was noted in creatinine clearance by 24 hours; these changes were not statistically or clinically significant. No difference was noted between the groups, suggesting that generous fluid replacement alone was as effective as fluid combined with low-dose dopamine. The difference from baseline was maintained at 5 days in the placebo group (but not in the dopamine group), but it also was not statistically significant. The study was not large enough to detect any decrease in the incidence of renal failure, which is an uncommon complication of elective abdominal aortic surgery. Although the differences in urine production and fluid requirements were not statistically different, the trend suggested that the addition of dopamine might allow the production of more urine per unit of fluid infused. The mechanisms by which dopamine increases urine production are related to an increase in the glomerular filtration rate, which is largely attributable to increased cardiac output [14], and to a direct action on tubular sodium uptake mechanisms leading to natriuresis. Normal tubuloglomerular feedback (which regulates glomerular filtration rate in response to filtered sodium load) is blunted in the presence of dopamine, which further enhances its diuretic action [15]. This trend in favor of dopamine was of no clinical significance in the context of this study, although it does support the view that in euvolemic patients, dopamine has a mild diuretic effect. A similar diuretic effect might have deleterious consequences in hypovolemic patients by worsening the hypovolemia. It is therefore essential to exclude hypovolemia before resorting to dopamine in oliguric patients. When considering the use of dopamine in this context, the cost and adverse effects (such as arrhythmias, depression of respiratory drive, increased intrapulmonary shunt, myocardial ischemia in patients with obstructive coronary artery disease, and increased pulmonary wedge pressure) need to be considered. Four patients in the study had postoperative myocardial infarction. The relatively high rate of myocardial infarction may reflect the inadequate cardiac resources available locally, which severely limit the number of patients who can be investigated and treated for active ischemic heart disease before aortic surgery. Although the numbers were too small for meaningful comparison, three of the patients with myocardial infarction were from the dopamine group, which raises some questions about the safety of dopamine in such patients. Although the study was small and without the power to discriminate different rates of renal failure (an infrequent clinical end point), we did not find any compelling evidence to support the routine use of dopamine in

Use of monoethylglycinexylidide as a liver function test in the liver transplant recipient.

The hepatic conversion of lignocaine to monoethylgly-cinexylidide (MEGX) has been used as a real time monitor of liver function in liver transplant recipients. Data are reported for the first 4 weeks after transplant in 50 consecutive orthotopic liver grafts in 47 adults. The MEGX concentration was significantly depressed by approximately 50% in those patients in whom there was a complicated clinical course (excluding steroid-sensitive rejection) after transplantation, compared with patients in whom major complications did not occur. The MEGX concentration in the recipients after transplant was independent of the donor MEGX concentration, but, in addition to the patients clinical status, was strongly influenced by the recipients pretransplant biochemical profile, being inversely related to the pretransplant bilirubin concentration. MEGX concentrations < 25 μg/L in the first 36 hr after revascularization were predictive of greater morbidity and mortality.

Intestinal Pseudo-Obstruction Following the Use of Enterai Charcoal and Sorbitol and Mechanical Ventilation with Papaveretum Sedation for Theophylline Poisoning

SummaryWe report 2 cases of intestinal pseudo-obstruction, 1 fatal, which developed following the use of enterai activated charcoal with sorbitol, and mechanical ventilation with papaveretum (‘Omnopon’) sedation for the treatment of severe theophylline self-poisoning. While mechanical intestinal obstruction may rarely complicate the use of enterai activated charcoal, pseudo-obstruction has not been previously described. Causal mechanisms and prophylaxis are discussed, highlighting a possible interaction between theophylline and papaveretum, and the dangers of multidose enterai charcoal with sorbitol in this context.

The use of the lidocaine-monoethylglycinexylidide test in the liver transplant recipient.

The lidocaine-monoethylglycinexylidide (MEGX) test is used to monitor liver function in liver transplant recipients. Serial studies have been undertaken after 155 allografts. The initial MEGX concentration is significantly correlated with the donor MEGX concentration. It is also influenced by the recipients pretransplant bilirubin concentration, being lowest among patients with very high bilirubin levels. Use of segmental grafts is also accompanied by low MEGX concentrations. The flow-dependent clearance of lidocaine makes it a sensitive indicator of disturbed liver blood flow, with decreased MEGX concentrations occurring in hepatic artery thrombosis and rejection and as a result of cardiac failure and pulmonary effusions. Significant hepatic ischemia resulting in delayed initial function or cholestasis also is associated with low MEGX concentrations. The initial median MEGX concentrations were lowest among patients who required retransplantation or who died within 2 months of allografting.

Effect of postoperative low-dose dopamine on renal function after elective major vascular surgery

OBJECTIVE To determine the effect on renal function of postoperative low-dose dopamine in volume-replete patients after elective, major vascular abdominal surgery. DESIGN Randomized, double-blind, placebo-controlled trial. SETTING Intensive care unit of a referral hospital in Brisbane, Australia. PATIENTS 37 patients having elective repair of an abdominal aortic aneurysm or having aortobifemoral grafting; 18 received dopamine, and 19 received placebo. Two patients were excluded from the 5-day analysis because of perioperative death. INTERVENTIONS Patients were randomly assigned to receive either placebo or a low-dose infusion of dopamine (3 micrograms/kg per minute) in saline. Patients in both groups were given sufficient crystalloid to maintain a urine flow of more than 1 mL/kg per hour during the first 24 postoperative hours. Care in the intensive care unit was otherwise usual and was the same for each group. MEASUREMENTS Plasma creatinine levels, urea levels, and creatinine clearance were measured preoperatively and postoperatively (at 24 hours and 5 days). Urine flow and the volume of crystalloid during the first 24 hours were recorded. RESULTS Two postoperative deaths occurred in the dopamine group (from renal failure and myocardial infarction). Four patients had myocardial infarction, three of whom received dopamine. Plasma creatinine levels remained unchanged in both groups. At 24 hours, the mean plasma urea level decreased by 1.07 mmol/L in the dopamine group compared with 1.84 mmol/L in the placebo group, a difference of 0.77 (95% CI, -0.12 to 1.67). The mean 24-hour creatinine clearance increased by 0.165 mL/s (9.89 mL/min) in the dopamine group and by 0.199 mL/s (11.98 mL/min) in the placebo group (P > 0.2). Urine volumes were slightly higher in those receiving dopamine (1.83 mL/kg compared with 1.6 mL/kg, a difference of 0.23 [CI, -0.18 to 0.64]). None of these differences were statistically or clinically significant. CONCLUSIONS Within the limits of the small size of the study, low-dose dopamine appeared to offer no advantage to euvolemic patients after elective abdominal aortic surgery. However, patients with acute oliguric renal failure were not included in the study.