Preferences for CPR and life-sustaining treatment among nursing home residents.
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Aged↗
Biomedical subjects
M Hilberman
Publications and source records attributed to M Hilberman.
Cost savings at the end of life.
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Cost Savings↗
Capnometer readings at high altitude.
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Altitude↗
Recovery of cardiopulmonary reflexes in monkeys undergoing heart-lung transplantation.
After heart-lung transplantation in primates, cardiopulmonary reflexes were tested and shown to be present. The Hering-Breuer and cough reflexes were tested, as well as responses to an inhaled respiratory stimulant, vasodilator, and an intravenous anticholinesterase and antimuscarinic agent. Recovery of these responses, except to the anticholinesterase agent, suggests that reinervation occurs in autotransplanted organs in primates. The Hering-Breuer reflex was present at 1.9 and 2.2 months after the operation in two animals subjected to autotransplantation. These cardiopulmonary reflex responses were also demonstrated in two allograft recipients studied at 15 and 16.9 months after the operation. Return of protective reflexes such as coughing may be an important mechanism to prevent aspiration pneumonitis and other complications in humans.
Ammonia↗
Relationship between intracellular pH and energy metabolism in dog brain as measured by 31P-NMR.
The relationships between pHi (intracellular pH) and phosphate compounds were evaluated by nuclear magnetic resonance (NMR) in normo-, hypo-, and hypercapnia, obtained by changing fractional inspired concentration of CO2 in dogs anesthetized with 0.75% isoflurane and 66% N2O. Phosphocreatine (PCr) fell by 2.02 mM and Pi (inorganic phosphate) rose by 1.92 mM due to pHi shift from 7.10 to 6.83 during hypercapnia. The stoichiometric coefficient was 1.05 (r2 = 0.78) on log PCr/Cr against pHi, showing minimum change of ADP/ATP and equilibrium of creatine kinase in the pH range of 6.7 to 7.25. [ADP] varied from 21.6 +/- 4.1 microM in control (pHi = 7.10) to 26.8 +/- 6.3 microM in hypercapnia (pHi = 6.83) and 24.0 +/- 6.8 microM in hypocapnia (pHi = 7.17). ATP/ADP X Pi decreased from 66.4 +/- 17.1 mM-1 during normocapnia to 25.8 +/- 6.3 mM-1 in hypercapnia. The ADP values are near the in vitro Km; thus ADP is the main controller. The velocity of oxidative metabolism (V) in relation to its maximum (Vmax) as calculated by a steady-state Michaelis-Menten formulation is approximately 50% in normocapnia. In acidosis (pH 6.7) and alkalosis (pH 7.25), V/Vmax is 10% higher than the normocapnic brain. This increase of V/Vmax is required to maintain cellular homeostasis of energy metabolism in the face of either inhibition at extremes of pH or higher ATPase activity.
Adenine Nucleotides↗
A prospective, randomized study of the effects of prostacyclin on neuropsychologic dysfunction after coronary artery operation.
This randomized, double-blind study was designed to evaluate the effect of prostacyclin (epoprostenol) on the incidence and severity of postoperative neuropsychologic dysfunction in patients undergoing coronary artery operation. Four days before operation and 1 week after operation, 100 patients having coronary artery bypass grafting underwent detailed neurologic and psychologic examinations and computed tomographic scans of the brain. The psychologic examination was repeated 2 months after operation. During cardiopulmonary bypass, all patients received 300 U/kg of heparin and then either buffer-diluent or prostacyclin (12.5 ng/kg/min from the time of heparinization until onset of cardiopulmonary bypass and 25 ng/kg/min during cardiopulmonary bypass). No deaths or major neurologic complications occurred in this series. Ninety-six patients completed the psychologic and neurologic evaluations 1 week after operation; 74 of these patients were evaluated psychologically 2 months after operation. Psychologic testing demonstrated similar declines in postoperative performance in both the prostacyclin-treated and the control groups; these changes were no longer present in either group 2 months after operation. Results of neurologic examinations and computed tomographic scans of the brain were unchanged. We conclude that the administration of prostacyclin during cardiopulmonary bypass in patients undergoing routine coronary artery operation has no effect on perioperative cognitive changes.
Adult↗
31P NMR detection of mobile dog brain phospholipids.
The in vivo dog brain 31P NMR spectrum has a large peak in the phosphodiester region accounting for more than 35% of the total observable phosphorus metabolites. It is possible to reduce the intensity of this peak by off-resonance saturation. To characterize the nature of this peak, extracts of dog brain frozen in situ were analyzed by high resolution 31P NMR. ATP, phosphocreatine, inorganic phosphate, and phosphomonoesters were recovered in appropriate amounts in the methanol:HCl extract. However, acid soluble phosphodiesters accounted for only 8% of the observable phosphorus. More NMR observable phosphodiesters were selectively recovered following CHCl3:methanol extraction of phospholipids. These results suggest that the in vivo phosphodiester resonance has substantial contributions from a fraction of mobile brain phospholipids.
Animals↗
A prospective, randomized study of the effects of prostacyclin on platelets and blood loss during coronary bypass operations.
A randomized, double-blind study was designed to evaluate the therapeutic effect and safety of prostacyclin (epoprostenol) in patients undergoing cardiopulmonary bypass. One hundred patients having isolated coronary bypass grafting received 300 units/kg of heparin and then either prostacyclin (12.5 ng/kg/min from heparinization until cardiopulmonary bypass, 25 ng/kg/min during bypass) or buffer/diluent in a similar manner. Standardized anesthetic, perfusion, and surgical techniques were used. Drug and placebo groups were similar in demographic data and bypass times, and there were no deaths. Activated coagulation time and platelet count were significantly higher during cardiopulmonary bypass in patients receiving prostacyclin. Platelet count remained significantly higher 24 hours after bypass in the active drug group. Immediately after operation, there was significantly less prolongation of bleeding time (1.3 versus 2.9 minutes; p = 0.009) in the patients receiving prostacyclin. Blood loss was significantly reduced during the first 4 hours postoperatively in the prostacyclin group (261 +/- 159 versus 347 +/- 197 ml; p = 0.02). There was no significant difference between the groups when total blood loss was compared (710 +/- 351 versus 869 +/- 498 ml; p = 0.07). Patients receiving prostacyclin required an average of 257 ml less blood transfused in the intensive care unit (p = 0.02). We conclude that the clinical impact of prostacyclin in patients undergoing coronary artery operations was demonstrable, but small. Prostacyclin may provide clinical benefits in patients undergoing cardiopulmonary bypass when there are contraindications to or other difficulties with blood transfusion. With prostacyclin, reduced heparin dose is possible and therefore reduced protamine requirement would offer a potential benefit of less cardiovascular depression immediately after bypass. However, the advantages offered by prostacyclin are not sufficient to recommend its routine use during cardiopulmonary bypass.
Adult↗
In vivo time-resolved brain phosphorus nuclear magnetic resonance.
Methods used to obtain and quantify high-quality time-resolved dog brain phosphorus nuclear magnetic resonance (31P NMR) spectra are described. In eight animals the normoxic dog brain spectra showed 10% of total phosphorus in ATP, 14% in phosphocreatine (PCr), and 38% in brain phospholipids containing phosphodiesters. The chemical shift between PCr and inorganic phosphate, 5.09, corresponded to an intracellular brain pH of 7.2. During hypoxia, PCr declined to 0.5 +/- 0.3 (n = 8) of starting levels, prior to any changes in brain ATP. Simultaneous recording of the EEG was obtained in two animals. During hypoxia, progressive PCr depletion was associated with progressive slowing of the EEG, which was essentially silent before significant changes occurred in brain ATP. Finally, the brain 31P NMR spectrum and pH were measured at 90-s intervals, and the sequential changes that followed respiratory arrest were monitored in one dog until high-energy phosphate depletion was complete.
Adenosine Triphosphate↗
The diuretic properties of dopamine in patients after open-heart operation.
Dopamine and dobutamine were administered to 12 patients who had undergone open cardiac operations. To eliminate the effects of variation in systemic blood flow upon renal function the drug infusion rates were adjusted to achieve equal cardiac outputs. Under conditions of equivalent systemic pressure and flow, dopamine (5.0 +/- 1 micrograms X kg-1 X min-1) and dobutamine (3.5 +/- 1.8 micrograms X kg-1 X min-1) had similar effects upon glomerular filtration rate (90 +/- 29 vs. 83 +/- 27 ml X min-1 X 1.73 m-2) and effective renal plasma flow (375 +/- 119 vs. 357 +/- 126 ml X min-1 X 1.73 m-2). However, dopamine administration resulted in a significantly greater diuresis (2.8 +/- 2.7 vs. 1.0 +/- 0.3 ml/min), natriuresis (0.32 +/- 0.39 vs. 0.07 +/- 0.10 mEq Na+/min), and kaliuresis (0.15 +/- 0.06 vs. 0.10 +/- 0.03 mEq K+/min) (P less than 0.05). In patients with modest depression of cardiac performance and renal vasoconstriction, dopamine's selective renal vasodilator effects were not evident. Furthermore, these data suggest that dopamine inhibits tubular solute reabsorption directly. Thus, the diuresis and natriuresis that frequently accompany dopamine administration may occur independently of any effects of dopamine upon renal blood flow.
Adult↗
Glomerular and tubular function in non-oliguric acute renal failure.
Glomerular and tubular function were evaluated in 30 non-oliguric patients with increasing azotemia following open heart surgery. Fractional clearances (theta) of test solutes relative to that of inulin were determined. In 16 patients, theta dextran (radius 22 to 30 A) exceeded unity, a finding attributed to inulin backleak through necrotic tubules. These patients were classified as having acute renal failure; 14 subsequently required dialysis. In the remaining patients (N = 14), theta dextran was normal. These patients were considered to have prerenal failure; all recovered spontaneously. clearance of inulin (Cin) was lower in acute renal failure than in prerenal failure (12 +/- 2 versus 18 +/- 2 ml/min/1.73 m2; p less than 0.025). The apparent difference in glomerular filtration rate when Cin is used as an index was abolished, however, when Cin in acute renal failure was corrected for tubule backleak of inulin. In acute renal failure, fractional clearance of p-aminohippurate (theta PAH) was 7.1 +/- 1.0, and fractional excretion of potassium (FEk) was 160 +/- 18 percent. These findings strongly suggest that secretory ability in both proximal and terminal tubule augments, respectively, is preserved in acute renal failure. Compared with prerenal failure, the urine-to-plasma inulin ratio was lower (U/Pin = 10 +/- 1 versus 25 +/- 4; p less than 0.005) and FENa was higher (FENa = 5.1 +/- 1.5 versus 0.5 +/- 1.0 percent; p less than 0.01) in acute renal failure.
Acute Kidney Injury↗
Dynamics of glomerular ultrafiltration following open-heart surgery.
To elucidate how individual determinants might lower the rate of glomerular ultrafiltration (GFR) in some patients following cardiac surgery, we performed hemodynamic measurements and clearance of inulin (as a measure of GFR), PAH (as a measure of effective renal plasma flow [ERPF]), and dextran-40. Two groups of 17 patients each were distinguished by the presence or absence of prerenal azotemia. Glomerular hypofiltration (GFR = 21 +/- 2 vs. 76 +/- 6 ml/min/1.73 m2, P less than 0.001) in the former was accompanied by depressed left ventricular function, arterial pressure, and ERPF (152 +/- 26 vs. 317 +/- 32 ml/min/1.73 m2, P less than 0.001). To determine if factors beside ERPF play a role in lowering GFR, we calculated the efferent oncotic pressure (pie). Failure of GFR to change over a 24-hour period despite increases in ERPF suggested that both patient groups were at filtration pressure disequilibrium (FPD). This condition permits calculation of a unique glomerular ultrafiltration coefficient (Kf). Over a range of pressures for transcapillary hydraulic pressure (deltaP), such that 3 less than or equal to (deltaP - pie) less than or equal to 10 mm Hg (to simulate FPD), Kf was less than 0.08 ml . sec-1 . mm Hg-1 . 1.73 m-2 in azotemic, but exceeded this value in nonazotemic patients. Although a selective reduction of Kf is predicted to lower the fractional clearance of dextrans, these were significant elevated in azotemic relative to nonazotemic patients (molecular radii 30 - 40 A). A theoretical analysis of the latter data suggests that over the foregoing range of FPD, a 15 to 30% decline in deltaP combined with a 30 to 0% reduction in Kf from values in nonazotemic patients best explains the experimental findings in azotemic patients.
Cardiac Surgical Procedures↗
The renal effects of sodium nitroprusside in postoperative cardiac surgical patients.
Sodium nitroprusside (SNP) is frequently used to control hypertension and/or improve systemic blood flow following cardiac operations. Although SNP causes renal vasodilation when infused into isolated kidneys, the reported effects of SNP on renal vascular resistance and blood flow in intact animals and humans have varied. To define the effects of SNP in postoperative cardiac surgical patients, renal clearances and hemodynamics were measured in seven patients within 24 hours of coronary bypass grafting. Studies were delayed until patients were stabilized and had rewarmed following operation. Following baseline measurements (off SNP), SNP infusion was used to lower mean arterial pressure to 85 torr. Pulmonary wedge pressure was maintained by appropriate fluid therapy, and the measurements repeated 1 h later. SNP administration resulted in equivalent decreases in renal (-31 per cent), pulmonic (-29 per cent) and systemic (-33 percent) vascular resistance. Notwithstanding the decrease in arterial pressure (109 +/- 14 to 91 +/- 9 torr, P less than 0.01), renal blood flow increased by 20 per cent (653 +/- 193 to 792 +/- 210 ml . min-1 . 1.73 m-2, P less than 0.02), in direct proportion to the increase in cardiac index (2.5 +/- 0.4 to 3.0 +/- 0.3 1 . min-1 . m-2, P less than 0.01). Thus, in postoperative cardiac surgical patients, SNP administration can be expected to improve renal blood flow, so long as left atrial hypotension is avoided, and the decline in systemic arterial pressure is not excessive. The improvement in renal blood flow achievable with SNP may be critical for patients with severely depressed left ventricular function in whom severe depression of renal blood flow may occur as an antecedent to acute renal failure.
Acute Kidney Injury↗
Effect of the intra-aortic balloon pump upon postoperative renal function in man.
Fifty-seven postoperative cardiac surgical patients receiving intra-aortic balloon pump (IABP) support were selected for detailed hemodynamic and renal function measurements on the basis of depressed cardiac and/or renal function. Eleven patients developed acute renal failure while receiving maximal IABP support and 10 during, or after withdrawal of IABP support. To define further the relationship between IABP support and renal function, 17 patients underwent simultaneous assessment of hemodynamic and renal function under varying conditions of IABP support. These studies, performed just before IABP withdrawal, demonstrated slight, clinically insignificant, improvement in hemodynamic and renal function with increased IABP support. Arterial pressure recordings, performed above and below the intra-aortic balloon in 8 patients, revealed no significant pressure gradient across the balloon whether single- or double-chambered. In addition, the balloon pulse waveform was always evident in the femoral artery. Importantly, the intra-aortic balloon did not interfere demonstrably with renal function, nor did it decrease renal perfusion pressure, in spite of its suprarenal position. Therefore, improvement in systemic perfusion from IABP support in the early postoperative period will result in improved renal perfusion.
Acute Kidney Injury↗
Pathophysiology of hemodynamically mediated acute renal failure in man.
A tubular injury characterized by intraluminal obstruction and transtubular backleak of glomerular filtrate occurs in experimental acute renal failure (ARF) in animals. To determine whether these alterations also occur in human ARF, we studied 44 patients developing nonoliguric ARF following cardiac surgery. The delay in appearance of i.v. administered inulin in urine (Tu) was used as a measure of tubular fluid flow rate. Tu was not longer in 13 ARF patients than it was in control subjects (7.2 vs 9.0 min), suggesting that at least a subpopulation of tubules was widely patent. The fractional urinary dextran clearance profile (thetaD; radii, 20 to 40 A) was then determined in 20 patients with sustained ARF in whom inulin clearance averaged 11 +/- 1 ml/min/1.73 m2. A mass conservation model, which assumes that thetaD in Bowman's space in ARF is the same as that measured in controls, when applied to the experimental observations revealed that, on the average, 42% of filtered inulin was lost by transtubular backleak. A similar fractional inulin backleak (38%) persisted in 11 additional patients in whom ARF had begun to recover and in whom inulin clearance averaged 26 +/- 3 ml/min/1.73 m2. These findings suggest that in hemodynamically-mediated and nonoliguric ARF, (1) tubular obstruction is not homogeneous, and (2) backleak of glomerular filtrate contributes to but does not fully account for depression of inulin clearance.
Acute Kidney Injury↗
Albuminuria and the permselective properties of the glomerulus in cardiac failure.
Fractional dextran clearances (theta D) were used to ascertain whether the albuminuria accompanying cardiac failure (CF) has a hemodynamic basis. In 17 patients with grade-IV CF in whom GFR and effective renal plasma flow (ERPF) were depressed to 58 +/- 7 and 215 +/- 20 ml/min/1.73 m2, respectively, theta D was elevated relative to normal control subjects over the Stokes-Einstein radius (r) interval of 28 to 46 Angstrom. For dextran of equivalent size to albumin (r = 36 Angstrom), the rate of urinary excretion (UD36V) was not increased because elevated theta D36 was offset by the depressed GFR. In contrast, urinary albumin excretion (UalbV) was increased to 82 +/- 35 microgram/min. Thus, for albuminuria in CF to have the hemodynamic basis suggested by elevation of theta D requires that (I) the fractional clearance for anionic albumin be disproportionately enhanced relative to uncharged dextran by reduced glomerular plasma flow and/or (2) that glomerular electrostatic barrier function be impaired in CF. In seven patients with minimal change nephropathy, UD36V was similar to that in CF, but UalbV was 40 times greater than that in CF. Thus, if glomerular electrostatic barrier function is impaired in CF, such dysfunction is trivial by comparison with minimal change nephropathy.
Adolescent↗
Neurologic dysfunction following cardiac operation with low-flow, low-pressure cardiopulmonary bypass.
A prospective 6 month study of all patients undergoing cardiac operation with cardiopulmonary bypass (CPB) was undertaken to determine the incidence of neurologic and neuropsychological dysfunction following low-flow, low-pressure CPB. Among 204 patients who underwent cardiac operation with CPB, there were seven deaths (3.4%), six who developed new motor deficits (2.9%), and 35 (17.2%) who exhibited some neurologic or neuropsychological dysfunction at discharge. When compared to the 169 patients with no evidence of neurlogic or neuropsychological dysfunction at discharge, these 35 were older (65 +/- 10 versus 55 +/- 12 years), had a lower incidence of coronary artery bypass grafting as the sole surgical procedure (29% versus 55%), a higher mortality rate (11.4% versus 1.8%), and prolonged CPB (140 +/- 45 versus 107 +/- 38 minutes). The mean arterial pressure (MAP) during CPB was similar in the two groups (51 +/- 7 versus 49 +/- 7 torr), and an index of time at low pressure, torr x minutes below 50 (TM less than 50), was also similar in the two groups (589 +/- 591 versus 554 +/- 478 TM less than 50). The incidence of postoperative neurologic and neuropsychological complications appears comparable to that in reports from institutions employing high CPB flow and maintaining high CPB MAP. Our results suggest that CPB pressure, per se, is not the major determinant of postoperative neurologic and neuropsychological dysfunction.
Amnesia↗