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Biomedical subjects

R F Davis

Publications and source records attributed to R F Davis.

At least 37 records · Page 2Linked to original sources
PubMed1994

"Normothermic range" temperature affects myocardial infarct size.

OBJECTIVES: This study tested the hypothesis that small changes in temperature above the hypothermic range may alter myocardial infarct size after acute coronary occlusion-reperfusion. A secondary hypothesis, that a correlation between temperature and infarct size may be independent of an associated change of heart rate, was also evaluated. METHODS: Eighteen pentobarbitone-anaesthetised, open chest rabbits underwent 30 min coronary artery occlusion and 3 h reperfusion at blood temperatures ranging from 35-42 degrees C, achieved and maintained using surface methods (not paced, group NP). In a second group of 11 animals, heart rate was held constant across the same range of temperatures (paced, group P), before and throughout coronary artery occlusion-reperfusion. Infarct sizes were assessed by the tetrazolium method. RESULTS: Target temperature was effectively controlled over the duration of the experimental protocol to within +/- 0.25 degrees C. Area at risk did not vary with temperature. Infarct size, normalised to area at risk, was correlated with temperature in both groups (infarct size = 7.9 x temp-250.0, r = 0.75, p = 0.0003, group NP; infarct size = 11.7 x temp-404.5, r = 0.88, p = 0.0004, group P). There was no significant difference between the slopes of these two lines (p = 0.18), indicating that the positive correlation between infarct size and temperature is not related to changes of heart rate. CONCLUSION: Temperatures in the range of 35-42 degrees C affect myocardial infarct size significantly, independent of heart rate.

Animals↗
PubMed1994

Cardioprotection provided by adenosine receptor activation is abolished by blockade of the KATP channel.

Adenosine agonists and openers of the ATP-sensitive potassium (KATP) channel have been reported to limit infarct size (IS). We tested the hypothesis that these phenomena are interdependent. Anesthetized swine underwent 60 min of coronary artery occlusion and 90 min of reperfusion. Preconditioning was elicited by two cycles comprising 10 min of occlusion and 10 min of reperfusion (n = 7 swine). An intracoronary infusion of adenosine (Ado; n = 10) or (-)-N6-(2-phenylisopropyl)-adenosine (R-PIA; n = 7) replaced preconditioning ischemia. KATP channels were blocked with sodium 5-hydroxydecanoate (5-HD) in the absence (n = 6) or presence (n = 8) of R-PIA. Control pigs (n = 7) received saline vehicle. IS was assessed with tetrazolium and normalized as percentage of area at risk. Preconditioning resulted in a reduced IS compared with Control (3.9 +/- 1.8 vs. 43.5 +/- 6.9%, respectively; P < 0.0005). Ado and R-PIA also reduced IS [21.1 +/- 6.8 (P < 0.01) and 11.2 +/- 7.4% (P < 0.005), respectively]. 5-HD alone did not alter IS, but it abolished R-PIA-induced cardioprotection (IS 5-HD + R-PIA = 48.6 +/- 13.2%). Thus Ado A1-receptor agonists mimicked the cardioprotection of ischemic preconditioning. The Ado-induced limitation of IS was abolished by blockade of the KATP channel. We conclude that both Ado A1 receptors and KATP channels may be involved in ischemic preconditioning.

Adenosine↗
PubMed1994

Midazolam produces vasodilation by mixed endothelium-dependent and -independent mechanisms.

Aortic rings were obtained from rat thoracic aorta and studied in vitro with and without functionally intact endothelium to determine whether "the mechanism" requires endothelium [or endothelium-derived relaxing factor (EDRF)]. In aortic rings precontracted with either phenylephrine (PE, 3 x 10(-8)-3 x 10(-7) mol/L) or KCl (40 mmol/L), midazolam produced concentration-dependent relaxation, with and without endothelium. Rings without endothelium demonstrated significantly less relaxation than those with endothelium regardless of whether they were precontracted with PE or KCl. With intact endothelium, midazolam produced greater relaxation in PE-contracted aortic rings than in KCl-contracted aortic rings; the midazolam concentration producing 50% relaxation from the contracted state (RC50) was 8.8 +/- 3.6 x 10(-7) mol/L for PE-contracted rings and 3.3 +/- 1.1 x 10(-6) mol/L for KCl-contracted rings (P < 0.05). In aortic rings with intact endothelium pretreated with NG-monomethyl-L-arginine (L-NMMA, 10(-4) mol/L), an inhibitor of nitric oxide (NO) synthesis, midazolam produced relaxation of similar magnitude to that seen in the denuded aortic rings except at the highest concentration (1 x 10(-5) mol/L). Pretreatment with the cyclooxygenase inhibitor, indomethacin (2.5 x 10(-5) mol/L), did not change the midazolam-induced relaxation in rings with intact endothelium as compared to untreated control aortic rings. In contrast to the intact endothelium state, when endothelium was removed, midazolam produced greater relaxation in the KCl-contracted aortic rings than in PE-contracted rings (RC50, 1.2 +/- 0.3 x 10(-5) mol/L vs 2.3 +/- 0.4 x 10(-5) mol/L, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Propofol produces endothelium-independent vasodilation and may act as a Ca2+ channel blocker.

The mechanism of vasodilation induced by propofol was investigated using isolated rat thoracic aortic rings. Aortic rings were precontracted with potassium chloride (KCl) (40 mM) or phenylephrine (PE) (3 x 10(-8) to 3 x 10(-7) M) in the presence and absence of intact endothelium. Propofol produced similar concentration-dependent relaxation in aortic rings with and without endothelium regardless of whether they were precontracted with KCl or PE. The relaxation response to propofol was significantly greater in KCl-contracted aortic rings than in PE-contracted aortic rings. The propofol concentration producing 50% relaxation from the contracted state (RC50) was lower in aortic rings contracted with KCl than with PE, both with (5 +/- 0.6 x 10(-5) M vs 8.3 +/- 5.7 x 10(-4) M, P < 0.001) and without intact endothelium (3.9 +/- 0.5 x 10(-5) M vs 7.2 +/- 3.8 x 10(-4) M, P < 0.001). Propofol inhibited the Ca(2+)-induced contractions of aortic rings exposed to Ca(2+)-free media and depolarized with KCl (40 mM, 100 mM) in a dose-dependent manner. These effects are similar to those produced by verapamil. Propofol (5 x 10(-5) M) had minimal effect on the intracellular Ca2+ release elicited by PE (10(-5) M). We conclude that vasodilation produced by propofol is not endothelium-dependent but is likely due to blockade of voltage-gated influx of extracellular Ca2+.

Animals↗
PubMed1991

Fusion of the occiput to the upper cervical spine. A review of 37 cases.

This is the first report of a large series of patients undergoing preoperative traction to reduce spinomedullary compression from cranial settling. In all cases, an attempt was made to reduce the malalignment with Gardner-Wells or halo traction before posterior fusion. One patient required an anterior retropharyngeal decompression of the odontoid performed as a one-stage procedure at the time of the posterior operation, and two required subsequent anterior transoral-transpharyngeal resection of the odontoid. From 1974 to 1989, 37 patients underwent posterior occipital cervical arthrodesis. All cases presented with neurologic deficit, and most had signs of brain stem compression, such as L'hermitte's sign or Ondine's curse. The most common cause of basilar impression was rheumatoid arthritis, neoplastic destruction, previously failed C1-C2 fusion, or Down's syndrome. Mean postoperative follow-up was 2 years and 10 months; the patients with less than 2 years' follow-up were followed until successful fusion. Eight of 9 patients with L'hermitte's sign or Ondine's curse and 10 of 12 patients with intractable occipital pain were relieved of their symptoms after reduction and triple-wire stabilization-fusion. Eighteen of 25 patients with long tract signs improved after surgery. Interestingly, 14 (93.3%) of 15 patients with myelopathy improved when successful preoperative reduction of their deformity occurred, whereas only 4 (40%) of 10 patients with fixed basilar impression improved (chi 2 = 8.57, P = .014). Symptoms such as Ondine's curse, L'hermitte's sign, intractable occipital headache, and myelopathy are usually relieved by skeletal traction and posterior fusion without need of an additional transmucosal anterior procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Prolonged neuromuscular blockade and ventilatory failure after renal transplantation and cyclosporine.

In a retrospective one-year study, we documented respiratory failure or prolonged neuromuscular blockade in eight of 65 patients with chronic renal failure who had received either vecuronium (four of 29 patients) or atracurium (four of 36 patients) during anaesthesia for kidney transplantation. We reviewed the charts of the patients and recorded all aspects of medication and anaesthesia to try to determine whether there might be a single factor associated with this high incidence (12 per cent) of respiratory failure. Anaesthesia for all patients was induced with thiopentone, isoflurane, and N2O/O2. Tracheal intubation was facilitated with muscle relaxants in a single bolus of vecuronium, 0.07 to 0.1 mg.kg-1, or atracurium, 0.3 to 0.5 mg.kg-1. Additional doses were given according to neuromuscular activity, which was monitored visually by response to train-of-four and tetanic stimulation. Anaesthesia was maintained with fentanyl/isoflurane and N2O/O2. After induction of anaesthesia, each patient received methylprednisolone, cefazolin, mannitol infusion for 24 hr beginning at the start of renal artery anatomosis, and either azathioprine (n = 57) or cyclosporine (n = 8). Relaxation was evaluated toward the end of the operation by train-of-four stimulation. Neuromuscular blockade was reversed with edrophonium (0.75-1 mg.kg-1) or neostigmine (0.06-0.08 mg.kg-1). The eight patients with prolonged neuromuscular blockade received ventilatory support for one to three hours after operation. Respiratory failure was significantly more frequent in patients who received cyclosporine (P less than 0.05).

Adult↗
PubMed1990

Pseudarthrosis of the cervical spine after anterior arthrodesis. Treatment by posterior nerve-root decompression, stabilization, and arthrodesis.

Nineteen consecutive patients who had a symptomatic pseudarthrosis after a failed anterior cervical arthrodesis were treated by a posterior nerve-root decompression and arthrodesis. The indications for the operation were radiculopathy in the absence of myelopathy and evidence of a pseudarthrosis on lateral flexion and extension radiographs. The average duration of follow-up was forty-four months (range, twenty-four to fifty-four months). A solid fusion was achieved in all patients, and the radiculopathy was relieved in all but one. The motor weakness that had been present in four patients preoperatively resolved completely.

Adult↗
PubMed1989

Direct cannulation of myocardial blood vessels without interfering with regional blood flow distribution, resting blood flow, or reactive hyperemia.

An in vivo technique of directly cannulating coronary arteries and veins for sampling blood and measuring hemodynamic parameters is described. The cannulation procedure was evaluated for its effects on regional myocardial blood flow (RMBF), transmural RMBF distribution, and reactive hyperemia. In a group of ten dogs, RMBF was measured by using radionuclide microspheres. Values for left anterior descending (LAD) perfusion zone (with catheter) and circumflex (CX) zone (no catheter) did not differ significantly (119 +/- 14 mL/min/100 g v 123 +/- 14 mL/min/100 g, respectively). Likewise, endocardial-to-epicardial RMBF ratio was similar for the two areas (0.99 +/- 0.06 and 1.04 +/- 0.06, respectively). In five dogs, aortic and left ventricular pressures agreed closely with the LAD coronary artery pressure measured with the described catheter system. Arterial flow during rest and reactive hyperemia was measured in five additional dogs by using electromagnetic flow probes placed around the LAD and CX coronary arteries. During both rest and reactive hyperemia, flow was greater in the CX than in the LAD (65.46 +/- 4.12 and 169.62 +/- 9.04 in the CX v 30.24 +/- 0.78 and 102.28 +/- 5.38 in the LAD; P less than 0.05 for both); however, the percentage change from rest to reactive hyperemia was similar for both vessels. In each perfusion zone, flow during rest and reactive hyperemia and the percentage change were not affected by cannulation. The effects of an infusion of adenosine (20 to 40 micrograms/min) into the pulmonary artery with and without the LAD coronary catheters (artery and vein) were tested in six other dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1989

Lactate extraction fails to accurately reflect regional lactate production in ischemic myocardium.

Lactate extraction (defined as arteriovenous lactate concentration difference divided by arterial concentration and expressed as a percent) is often reported as the indicator of anaerobic cardiac metabolism in studies dealing with myocardial ischemia. However, lactate extraction ignores the effect of regional blood flow and, therefore, fails to consider the total mass of lactate consumed or produced (lactate flux). This study examined the relationship between lactate flux and calculated lactate extraction. Fourteen anesthetized dogs were instrumented to allow sampling of blood from the left anterior descending coronary artery (LADa) and vein (LADv) and a circumflex coronary vein (CFXv), as well as measurement of regional myocardial blood flow (RMBF) using microspheres, and measurement of systemic hemodynamic variables. Complete data sets (before LADa occlusion, after 15 minutes of LAD occlusion, and after 1 hour of reperfusion) were obtained in nine dogs. Only minor systemic hemodynamic changes occurred during LADa occlusion when compared with "before" and "after" values. Likewise, LADa occlusion produced only minor alterations in blood gas tensions, pH, concentrations of glucose, lactate, and RMBF in samples from the CFX perfusion zone. In contrast, LAD occlusion decreased RMBF in the LADa perfusion zone and produced significant hypercarbia and acidemia, as well as an increased LADv lactate concentration. In the LAD zone, lactate extraction decreased significantly from 15.9% +/- 7.0% before LAD occlusion to -77.4% +/- 21.8% during LAD occlusion (P less than 0.05). However, lactate flux (arteriovenous concentration difference x RMBF) in the LAD zone before and during LAD occlusion was not statistically significantly different (1.3 +/- 0.8 mg/min/100 g and -1.5 +/- 0.8 mg/min/100 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effect of isoflurane on the extent of myocardial necrosis and on systemic hemodynamics, regional myocardial blood flow, and regional myocardial metabolism in dogs after coronary artery occlusion.

Anesthetized dogs were studied in two protocols to determine the effect of isoflurane on the extent of myocardial injury resulting from left anterior descending coronary artery (LAD) occlusion. In 22 dogs (11 treated with isoflurane 1% inspired, beginning 1 hr after LAD occlusion, and 11 control) myocardial infarct size measured postmortem after 6 hr of LAD occlusion was significantly less with isoflurane than without it, 23.4 +/- 3.8% vs 36.2 +/- 2.4% of left ventricle; regional myocardial blood flow (RMBF) did not differ between groups and hemodynamic differences were slight. Fifty-two other dogs underwent two 15-min periods of LAD occlusion separated by 1 hr of reperfusion. Without isoflurane (n = 12), hemodynamic, RMBF, and regional metabolic data did not differ between the two occlusion periods. When isoflurane 1.3% inspired was administered during one of the two occlusion periods by random assignment, coronary perfusion pressure, left ventricular stroke work index, and systolic left ventricular pressure decreased more than when isoflurane was not administered. Both oxygen (O2) consumption and supply in ischemic myocardium decreased proportionately during LAD occlusion, but more so with isoflurane. Neither lactate production, potassium release, glucose extraction, nor coronary venous carbon dioxide (CO2) or O2 content differed between LAD occlusion periods with and without isoflurane. Thus, isoflurane decreased the extent of myocardial necrosis produced by LAD occlusion but neither RMBF nor metabolic indications were improved during transitory ischemia.

Animals↗
PubMed1988

Regional myocardial metabolism and electrolyte balance during acute ischemia in dogs.

The relationships among regional (ischemic and nonischemic) myocardial extracellular (coronary venous) potassium concentration, potassium-sodium concentration ratio, acid-base balance, and metabolism of glucose and lactate were evaluated in 14 anesthetized dogs in which ischemia was produced by transitory left anterior descending coronary artery (LAD) occlusion. Coronary blood samples were obtained from the specific regions by using coronary arterial and venous catheters placed directly into the vessel supplying (or draining) that region. During ischemia, in coronary venous blood sampled from the ischemic area, pH decreased, and PCO2, base deficit, potassium concentration, and the potassium-sodium ratio increased. In LAD venous blood samples obtained during LAD occlusion, the percentage change in potassium concentration was inversely related to the percentage change in PCO2 (r = -0.634, P < 0.05), but not to the percentage change in hydrogen ion concentration (r = -0.339, P > 0.05). During ischemia, arteriovenous O2 content difference in the LAD region increased from 8.54 +/- 0.73 vol % to 10.71 +/- 0.73 vol %; lactate extraction became negative (indicating net production), values decreasing from 27.76 +/- 4.49% to -138.10 +/- 16.81% (P < 0.05); and glucose extraction increased from 14.57 +/- 2.88% to 19.01 +/- 6.06% (0.05 < P < 0.1). These observations indicate that efflux of potassium from the myocardium during ischemia is linked to tissue hypoxia, increased glucose extraction, lactate production, and extracellular acidosis. A further contributor to potassium release, failure of the normal membrane-bound, energy-requiring ion pump, cannot be excluded by these data. With the model used in this study, blood can be sampled from discrete regions of the heart, which enables the study of interactions between pharmacologic agents, such as anesthetics, and the metabolic abnormalities produced by acute ischemia.

Acid-Base Equilibrium↗
PubMed1988

Esmolol decreases the adverse effects of acute coronary artery occlusion on myocardial metabolism and regional myocardial blood flow in dogs.

This study was designed to test the hypothesis that beta-adrenergic receptor blockade with esmolol would decrease the hemodynamic and myocardial metabolic impairment produced by left anterior descending coronary artery (LADa) occlusion. Twenty-three anesthetized open-chest dogs underwent direct cannulation of the LADa, its companion vein (LADv), and a distal circumflex vein (CFXv) for blood sampling. All dogs were subjected to two consecutive 15-minute periods of total LADa occlusion; group 1 (n = 11) received an infusion of esmolol (150 micrograms.kg-1.min-1) during either occlusion period (randomly assigned) and group 2 (n = 12) received no intervention during either occlusion period. One hour of reperfusion was interposed between the two periods of LADa occlusion. Hemodynamic measurements were made and blood was sampled from the aorta, CFXv, LADa, and LADv before and during both periods of LADa occlusion. Without esmolol infusion, LADa occlusion was associated with decreases in stroke index, coronary perfusion pressure, and left ventricular stroke work index; with esmolol infusion these hemodynamic decrements did not occur. During both LADa occlusion periods in both groups, lactate extraction became negative, i.e., there was net lactate production. Despite this, the magnitude of lactate production was less with esmolol than without it. Finally, average endocardial-to-epicardial blood flow ratio in the LAD perfusion area was decreased during each LAD occlusion period except when esmolol was infused, during which the baseline value was maintained. Thus, infusion of esmolol during temporary LADa occlusion preserved certain hemodynamic variables, preserved the ratio of endocardial-to-epicardial blood flow, and decreased the apparent magnitude of lactate production.

Analysis of Variance↗
PubMed1988

Differences in serum glucose determinations in infants with umbilical artery catheters.

Differences in serum glucose values obtained from different extremities in newborns with umbilical artery catheters (UAC) through which a dextrose solution was administered were studied. Control infants (n = 20) had no difference in simultaneous capillary glucose values obtained from both lower extremities. Infants with a low UAC had a significant difference between two (both lower extremities) or three (both lower and one upper extremity) simultaneous capillary glucose values. Infants with a high UAC did not. In the low UAC group, the serum glucose value was highest in the lower extremity through which the UAC entered the aorta and lowest in the upper extremity. The elevation in glucose value was related to the glucose infusion rate corrected for infant size (mg/kg/min). Clinicians caring for infants with low UACs should be aware of this potential error in order to prevent erroneous decision-making.

Blood Flow Velocity↗
PubMed1987

Methylene blue and indocyanine green artifactually lower pulse oximetry readings of oxygen saturation. Studies in dogs.

The effects of fluorescein, methylene blue, and indocyanine green on hemodynamic variables and on pulse oximetry and co-oximetry measurements of arterial hemoglobin oxygen saturation (SaO2) and oxyhemoglobin percentage (% HbO2) were evaluated in 16 anesthetized dogs in vitro by co-oximetry (% HbO2) and in vivo by pulse oximetry (SaO2). The light absorbance (optical density) in plasma (range 500 to 800 nm) was measured by a spectrophotometer. Fluorescein did not affect oximetry measurements, plasma light absorbance in the range measured, or hemodynamic variables. Methylene blue caused dose-dependent decreases in measurements made with both forms of oximetry for up to 30 minutes, the decrease being greater and longer lasting with pulse oximetry (P less than 0.05). Hemodynamic measurements in 5 dogs showed that methylene blue (1 to 5 mg/kg) increased arterial pressure transiently, after which cardiac output, stroke index, and left ventricular stroke work index decreased and left ventricular end-diastolic pressure and systemic and pulmonary vascular resistances increased (P less than 0.05 with 5 mg/kg). Methemoglobin concentration measured by co-oximetry increased significantly (to 19.9 +/- 1.4%, P less than 0.05) 1 minute after 5 mg/kg of methylene blue was injected. Methylene blue had a dose- and time-dependent effect on plasma light absorbance, and this effect peaked in the 660- to 670-nm range. The data do not distinguish the relative contributions of physiology (hemodynamic change), chemistry (methemoglobin production), and physics (optical properties) to the decrease in pulse oximetry and co-oximetry measurements that follows injection of methylene blue. Indocyanine green affected neither hemodynamic variables nor co-oximetry readings but decreased pulse oximetry readings for up to 10 minutes dose dependently.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Pulse oximetry fails to accurately detect low levels of arterial hemoglobin oxygen saturation in dogs.

The accuracy of two commercially available pulse oximeters (the Ohmeda Biox 3700, software version "J," and the Nellcor N-100) in detecting low levels of arterial hemoglobin oxygen saturation (SaO2) was evaluated in 10 dogs in which hypoxia was induced by stopping the fresh gas flow into the anesthesia machine circle system. Measurements made in vivo with the pulse oximeters, with detectors placed on the tongue, were compared with measurements made in vitro using an IL 282 CO-Oximeter as SaO2 decreased toward zero. Measurements from the two oximeters correlated poorly over the range from 0 to 100% SaO2 (r = 0.69). In this range, the correlation between Nellcor N-100 measurements and those of the CO-Oximeter had an r of 0.82, a regression line slope of 0.82, and a y intercept of 14.8; the correlation between the Ohmeda Biox 3700 and the CO-Oximeter had an r of 0.83, a regression line slope of 0.66, and a y intercept of 32.7. The correlation with the CO-Oximeter was similar for both the Ohmeda and the Nellcor pulse oximeters at an SaO2 of 80% or more. However, when SaO2 was less than 80%, measurements by pulse oximetry correlated less well with CO-Oximeter measurements (r = 0.62, slope = 0.64, and y intercept = 21.0 for Nellcor; r = 0.71, slope = 0.67, and y intercept = 32.4 for Ohmeda). When SaO2 was less than 60%, both oximeters inaccurately indicated the co-oximetry values (r = 0.36 and y intercept = 26.1 for the Nellcor; r = 0.48 and y intercept = 33.2 for the Ohmeda).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Influence of sterile protective sleeves on the sterility of pulmonary artery catheters.

Eighty-seven pulmonary artery catheters (PACs) with sterile protective sleeves were placed into 69 surgical ICU patients by one of the following two methods: through an introducer placed in a new, percutaneous site or by exchanging an indwelling catheter for an introducer. On removal, 5-cm catheter segments from the catheter tip and from within the introducer and sleeve, peripheral blood, and blood drawn from the PAC distal port were cultured quantitatively. Sleeve segment cultures were sterile if catheterization was less than 48 h and had been accomplished through a new percutaneous site. The risk of growing greater than 10(3) colonies on the tip and introducer segment increased to greater than 30% when PACs were left in over 96 h. The incidence of catheter-related bacteremia (CRB), defined as the simultaneous growth of identical organisms from the blood and the PAC tip, was 5.3% but may have been underestimated. CRB was associated with the use of corticosteroids (p = .009) and with cultures from any PAC segment growing more than 10(3) colonies (p less than .01). Although our data suggest that the use of the sterile protective sleeve is associated with a low risk of colonization, further study will be required to delineate the relationship between the use of protective sleeves and CRB.

Bacterial Infections↗
PubMed1987

Acute renal failure following traumatic injury or major operation.

Acute oliguria in the critically ill postoperative patient, or in the trauma victim after resuscitation, is a substantial clinical problem. The mortality associated with ARF in these settings remains unacceptably high. Evaluation of the oliguric patient must include thorough monitoring for, and correction of, prerenal and postrenal causes of oliguria. In this sense, diagnosis of ARF is one of exclusion. Differential diagnosis is facilitated by microscopic examination of urine and by biochemical analyses of blood and urine for calculating indices of tubular function (urinary-to-plasma ratios of blood urea nitrogen and creatinine, sodium excretion, and clearances of sodium, creatinine, solute, and water). The early detection of an intrarenal defect, as accomplished by using serial measurements of free water clearance, may allow interruption of the process and prevention of ARF. Preventive measures include optimization of hemodynamic status and the use of osmotic diuretic agents (mannitol) and loop diuretics (furosemide, ethacrynic acid, and bumetanide). Dopamine is useful for increasing both renal blood flow and urine flow and may be useful for preventing ARF, but this is not firmly established. Experimentally, other approaches such as modulating the renin-angiotensin system, prostaglandin system, and cellular calcium fluxes have been attempted, but the clinical applicability of these measures is not established. The best approach to ARF is preventing it by knowing which patients are at high risk, by studiously preventing renal insults, and by aggressively treating early indications of renal malfunction using established therapies.

Acute Kidney Injury↗