Rationing health care: the choice before us.

Rapid technological advances and upward pressure on wages of hospital personnel are leading to a steady increase in health care spending that is absorbing an ever-larger fraction of gross national product. Eliminating inefficiencies in the system can provide brief fiscal relief, but rationing of beneficial services, even to the well-insured, offers the only prospect for sustained reduction in the growth of health care spending. The United States, which has negligible direct experience with rationing, can learn about choices it will face from the experience of Great Britain where health care has been rationed explicitly for many years.

The influence of graded degrees of chronic hypercapnia on the acute carbon dioxide titration curve.

Studies were carried out to determine the influence of the chronic level of arterial carbon dioxide tension upon the buffering response to acute changes in arterial carbon dioxide tension. After chronic adaptation to six levels of arterial CO(2) tension, ranging between 35 and 110 mm Hg, unanesthetized dogs underwent acute whole body CO(2) titrations. In each instance a linear relationship was observed between the plasma hydrogen ion concentration and the arterial carbon dioxide tension. Because of this linear relationship, it has been convenient to compare the acute buffering responses among dogs in terms of the slope, dH(+)/dPaco(2). With increasing chronic hypercapnia there was a decrease in this slope, i.e. an improvement in buffer capacity, which is expressed by the equation dH(+)/dPaco(2)=-0.005 (Paco(2))(chronic) + 0.95. In effect, the ability to defend pH during acute titration virtually doubled as chronic Paco(2) increased from 35 to 110 mm Hg. The change in slope, dH(+)/dPaco(2), was the consequence of the following two factors: the rise in plasma bicarbonate concentration which occurs with chronic hypercapnia of increasing severity, and the greater change in bicarbonate concentration which occurred during the acute CO(2) titration in the animals with more severe chronic hypercapnia. These findings demonstrate the importance of the acid-base status before acute titration in determining the character of the carbon dioxide titration curve. They also suggest that a quantitative definition of the interplay between acute and chronic hypercapnia in man should assist in the rational analysis of acid-base disorders in chronic pulmonary insufficiency.

The nature of the renal adaptation to chronic hypocapnia.

Metabolic balance studies were carried out in normal dogs to define the renal mechanisms responsible for the adaptation to, and recovery from, chronic hypocapnia. A chronic reduction in arterial CO(2) tension (Pa(CO2)) of some 15 mm Hg was achieved by means of chronic exposure of the animals to 9% oxygen in an environmental chamber. The development of hypocapnia was associated with a marked suppression of net acid excretion which, together with a slight accumulation of organic acids, produced a reduction in plasma bicarbonate concentration (8 mEq/liter) that led to nearly full protection of extracellular pH (DeltaH(+) = - 2.5 nmoles/liter). When Pa(CO2) was returned to control levels, an augmentation of acid excretion restored plasma composition to normal after a brief period of "posthypocapneic metabolic acidosis."The changes in renal acid excretion during both adaptation and recovery were accomplished in a fashion notably different from that previously observed in chronic hypercapnia, being linked to changes in cation rather than chloride excretion. Thus, in dogs ingesting a normal NaCl diet, suppression of hydrogen ion excretion during adaptation to hypocapnia was associated with an increased excretion of sodium rather than with a retention of chloride. The fact that this loss of sodium occurred without a concomitant loss of potassium strongly suggests that the hypocapneic state specifically depressed distal sodium reabsorption; if distal sodium reabsorption had not been depressed, a reduction in proximal sodium reabsorption or a diminution in distal hydrogen ion secretion (or both) should have produced an increase in potassium excretion. The interpretation that chronic hypocapnia diminished sodium reabsorption was supported by the finding that when renal sodium avidity was enhanced by restriction of sodium intake, acid retention was accomplished by a loss of potassium rather than of sodium. The accompanying reduction in plasma bicarbonate concentration was slightly less than that observed in dogs ingesting a normal NaCl diet, a finding probably accounted for by a slight difference in the availability of cation for excretion under the two experimental circumstances. These findings, taken together with the observation that augmented acid excretion during recovery from hypocapnia is linked to cation retention, suggest that an adequate intake of cation during both adaptation and recovery from chronic hypocapnia may be critical to the physiologic regulation of acid-base equilibrium.

The effects of chronic hypoxemia on electrolyte and acid-base equilibrium: an examination of normocapneic hypoxemia and of the influence of hypoxemia on the adaptation to chronic hypercapnia.

We have carried out balance studies in normal dogs in order to appraise the effects of chronic hypoxemia on acid-base and electrolyte equilibrium. During the first phase of observation we produced a state of "pure" hypoxemia by reducing the oxygen concentration (utilizing nitrogen as a diluent) and by adding carbon dioxide to the environment in a concentration sufficient to keep arterial CO(2) tension (PCO(2)) within normal limits. The data demonstrate that such a 9-day period of normocapneic hypoxemia has no effect on electrolyte excretion and is virtually without effect on plasma composition. During the second phase of observation we subjected the hypoxemic dogs to stepwise increments in arterial carbon dioxide tension in order to evaluate the effects of the low oxygen tension on the acid-base adjustments to a chronic state of hypercapnia. At least 6 days was allowed for extracellular composition to reach a new steady state at each level of inspired carbon dioxide. The data demonstrate a rise in both plasma bicarbonate concentration and renal acid excretion that was not significantly different from that which has been described previously for hypercapnia without hypoxemia. Just as in these earlier studies, plasma hydrogen ion concentration rose with each increment in carbon dioxide tension, each millimeter Hg increment in PCO(2) leading to an increase in hydrogen ion concentration of 0.32 nmole per L. It thus appears that the chronic"carbon dioxide response curve" is not significantly influenced by moderately severe hypoxemia.

The maladaptive renal response to secondary hypocapnia during chronic HCl acidosis in the dog.

It has generally been thought that homeostatic mechanisms of renal origin are responsible for minimizing the alkalemia produced by chronic hypocapnia. Recent observations from this laboratory have demonstrated, however, that the decrement in [HCO(-) (3)], which "protects" extracellular pH in normal dogs, is simply the by-product of a nonspecific effect of Paco(2) on renal hydrogen ion secretion; chronic primary hypocapnia produces virtually the same decrement in plasma [HCO(-) (3)] in dogs with chronic HCl acidosis as in normal dogs (Delta[HCO(-) (3)]/DeltaPaco(2) = 0.5), with the result that plasma [H(+)] in animals with severe acidosis rises rather than falls during superimposed forced hyperventilation. This observation raised the possibility that the secondary hypocapnia which normally accompanies metabolic acidosis, if persistent, might induce an analogous renal response and thereby contribute to the steady-state decrement in plasma [HCO(-) (3)] observed during HCl feeding. We reasoned that if sustained secondary hypocapnia provoked the kidney to depress renal bicarbonate reabsorption, the acute salutary effect of hypocapnia on plasma acidity might be seriously undermined. To isolate the possible effects of secondary hypocapnia from those of the hydrogen ion load, per se, animals were maintained in an atmosphere of 2.6% CO(2) during an initial 8-day period of acid feeding (7 mmol/kg per day); this maneuver allowed Paco(2) to be held constant at the control level of 36 mm Hg despite the hyperventilation induced by the acidemia. Steady-state bicarbonate concentration during the period of eucapnia fell from 20.8 to 16.0 meq/liter, while [H(+)] rose from 42 to 55 neq/liter. During the second phase of the study, acid feeding was continued but CO(2) was removed from the inspired air, permitting Paco(2) to fall by 6 mm Hg. In response to this secondary hypocapnia, bicarbonate concentration fell by an additional 3.0 meq/liter to a new steady-state level of 13.0 meq/liter. This reduction in bicarbonate was of sufficient magnitude to more than offset the acute salutary effect of the hypocapnia on plasma hydrogen ion concentration; in fact, steady-state [H(+)] rose as a function of the adaptive fall in Paco(2), Delta[H(+)]/Delta Paco(2) = -0.44. That the fall in bicarbonate observed in response to chronic secondary hypocapnia was the result of the change in Paco(2) was confirmed by the observation that plasma bicarbonate returned to its eucapnic level in a subgroup of animals re-exposed to 2.6% CO(2). These data indicate that the decrement in plasma [HCO(-) (3)] seen in chronic HCl acidosis is a composite function of (a) the acid load itself and (b) the renal response to the associated hyperventilation. We conclude that this renal response is maladaptive because it clearly diminishes the degree to which plasma acidity is protected by secondary hypocapnia acutely. Moreover, under some circumstances, this maladaptation actually results in more severe acidemia than would occur in the complete absence of secondary hypocapnia.

Aldosterone in metabolic alkalosis.

Studies have been carried out in human volunteer subjects to evaluate the role of aldosterone in the development, maintenance, and correction of metabolic alkalosis induced by selective depletion of hydrochloric acid. During the first phase of our study the rate of aldosterone secretion was measured before the induction of alkalosis (while the subjects were on a low salt diet) and again after a steady state of metabolic alkalosis had been established. The data demonstrate a fall in aldosterone secretion from a value of approximately 500 mug/day to a value of approximately 200 mug/day. Thus, it appears that an increased rate of aldosterone secretion is not a prerequisite to the elevation of the renal bicarbonate threshold. During the second phase of our study, aldosterone was administered to the alkalotic subjects in doses of 1000 mug/day (or deoxycorticosterone acetate in doses of 40 mg/day) in order to determine the effects of a persistent steroid excess on the ability of sodium chloride to correct the acid-base disturbance. The data demonstrate that despite the administration of steroid, the ingestion of sodium chloride led to a reduction in plasma bicarbonate concentration from 39 to 29 mEq/liter, accompanied by a suppression of renal acid excretion. This reduction in plasma bicarbonate concentration occurred without a concomitant retention of potassium, a deficit of as much as 400-500 mEq of potassium persisting during repair of the acid-base disturbance. Our findings suggest that "saline-resistant" alkalosis, when it occurs in the absence of primary hyperadrenalism, cannot be attributed to aldosterone excess and/or potassium depletion of the magnitude seen in our study. We also suggest the need for a reappraisal of the way in which aldosterone excess contributes to the genesis and maintenance of alkalosis in primary aldosteronism.

A definition of proximal and distal tubular compliance. Practical and theoretical implications.

Micropuncture studies were carried out in the rat to evaluate the in situ distensibility characteristics of the proximal and distal tubules under a variety of experimental conditions. In the first phase, we determined the response of tubular diameter (D) to changes in tubular pressure (P) induced by partially obstructing single tubules. The response observed under these conditions (i.e., when interstitial pressure is presumed to be constant) has been defined as the compliance of the tubule. Over the range of tubular pressures studied (10-35 mm Hg for the proximal tubule, 5-25 mm Hg for the distal tubule) the compliance characteristics of the proximal and distal tubule were found to be markedly different; the proximal tubular pressure-diameter relationship was linear, DeltaD/DeltaP = 0.45 mum/mm Hg, whereas the distal pressure-diameter relationship was curvilinear, DeltaD/DeltaP = c(-0.1xP+2.2). In the second phase we used the compliance data to construct a series of theoretical pressure-diameter curves that define the response of the tubule to increments in interstitial as well as intratubular pressure. These curves indicate that changes in distal diameter should provide a sensitive index of a rise in interstitial pressure under conditions in which the transtubular pressure gradient is increased by a small amount, but that proximal diameter should provide a more sensitive index of changes in interstitial pressure when the transtubular pressure gradient is increased by a large amount. In subsequent experiments in which furosemide was administered, we observed that the pressure-diameter relationships for both the proximal and distal tubule were indistinguishable from the compliance curves, a finding consistent with the interpretation that interstitial pressure was not appreciably changed from control. By contrast, when mannitol was administered, both proximal and distal tubular pressure-diameter relationships were significantly altered in a fashion consistent with a large increase in interstitial pressure. Neither with furosemide nor mannitol administration did it appear likely that significant changes in tubular compliance could account for the observed behavior of the tubule.Finally, we propose that a knowledge of tubular compliance will be useful in exploring the interrelationships between tubular and peritubular pressures, tubular anatomy, and transtubular ionic permeability. Recent studies linking changes in the geometry of lateral intercellular spaces of the tubule to changes in passive ion movement suggest that an investigation of such anatomical-functional correlates should be productive.

The effect of chronic hypotonic volume expansion on the renal regulation of acid-base equilibrium.

Balance studies have been carried out to evaluate the influence of vasopressin-induced volume expansion on acid-base equilibrium in normal dogs and in dogs with steady-state metabolic acidosis induced by the administration of 5-7 mmoles/kg per day of hydrochloric acid.Hypotonic expansion in dogs with metabolic acidosis (mean plasma bicarbonate concentration 14 mEq/liter) produced a marked increase in renal acid excretion that restored plasma bicarbonate concentration to normal (20-21 mEq/liter) despite continued ingestion of acid. When water was restricted during the vasopressin period, and fluid retention thus prevented, no increase in acid excretion or plasma bicarbonate concentration occurred. From these findings we conclude that hypotonic expansion is a potent stimulus to renal hydrogen ion secretion and greatly facilitates the renal removal of an acid load. Normal dogs subjected to expansion demonstrated no change in net acid excretion or in plasma bicarbonate concentration even in the face of a marked diuresis of sodium and chloride and a reduction in plasma sodium concentration to approximately 110 mEq/liter. The animals did, however, regularly lose potassium, a finding that clearly indicates an acceleration of distal sodiumcation exchange. On the basis of these observations, and the findings in the expanded acidotic dogs, we suggest that in the expanded normal dogs acceleration of sodium-hydrogen exchange was responsible for preventing a bicarbonate diuresis and for stabilizing plasma bicarbonate concentration. These studies clearly demonstrate that chronic hypotonic expansion exerts a major influence on the renal regulation of acid-base equilibrium. The exact nature of the mechanism responsible for the increase in sodium-hydrogen exchange during hypotonic expansion remains to be determined.

Regulation of acid-base equilibrium in chronic hypocapnia. Evidence that the response of the kidney is not geared to the defense of extracellular (H+).

It is generally believed that the reduction in plasma [HCO3] characteristic of chronic hypocapnia results from renal homeostatic mechanisms designed to minimize the alkalemia produced by.the hypocapneic state. To test this hypothesis, we have induced chronic hypocapnia in dogs in which plasma [HCO3] had previously been markedly reduced (from 21 to 15 meq/liter) by the prolonged feeding of HCl. The PaCO2 of chronically acid-fed animals was reduced from 32 to 15 mm Hg by placing the animials in a large environmental chamber containing 9% oxygen. In response to this reduction in PaCO2, mean plasma [HCO3] fell by 8.6 meq/liter, reaching a new steady-state level of 6.4 meq/liter. This decrement in plasma [HCO3] is almost identical to the 8.1 meq/liter decrement previously observed in normal (nonacid-fed) animals in which the same degree of chronic hypocapnia had been induced. Thus, in both normal and HCl-fed animals, the renal response to chronic hypocapnia causes plasma [HCO3] to fall by approximately 0.5 meq/liter for each millimeter of Hg reduction in CO2 tension. By contrast, the response of plasma [H+] in the two groups was markedly different. Instead of the fall in [H+] which is seen during chronic hypocapnia in normal animals, [H+] in HCl-fed animals rose significantly from 53 to 59 neq/liter (pH 7.28-7.23). This seemingly paradoxical response is, of course, an expression of the constraints imposed by the Henderson equation and reflects the fact that the percent fall in [HCO3] in the HCl-fed animals was greater than the percent fall in PaCO2. These findings clearly indicate that in chronic hypocapnia the kidney cannot be regarded as the effector limb in a homeostatic feedback system geared to the defense of systemic acidity.

Renal regulation of acid-base equilibrium during chronic administration of mineral acid.

Previous studies in metabolic alkalosis have demonstrated that two factors are the prime determinants of acid excretion and bicarbonate reabsorption; first, the diversion to distal exchange sites of sodium previously reabsorbed in the proximal tubule and loop of Henle; and, second, a stimulus to sodium-cation exchange greater than that produced by a low-salt diet alone. In the present study we have examined the hypothesis that these two factors are also the prime determinants of acid excretion during the administration of mineral acid loads. To test this hypothesis, we have administered to dogs ingesting a low NaCl diet a daily dose of 7 meq/kg of H+ with anions (chloride, sulfate, or nitrate) whose differing degrees of reabsorbability influence the speed and completeness with which each is delivered to the distal nephron with its accompanying Na+. After 2-3 wk of acid administration, and after an initial urinary loss of Na+ and K+, the steady-state value for plasma [HCO3-] was 8.6 meq/liter below control in the HCl group, 3.7 meq/liter below control in the H2SO4 group, and unchanged from control in the HNO3 group; all of these values were significantly different from each other. We would propose the following explanation for our findings: when HCl is administered chronically, marked acidosis occurs because distal delivery of Cl- is restricted by the ease with which the Cl- can be reabsorbed in the proximal portions of the nephron. Only when Cl- retention produces sufficient hyperchloremia to insure delivery of Na+ (previously reabsorbed in proximal tubule and loop of Henle) to the distal nephron in quantities equal to ingested Cl is this primary constraint removed. In the case of sulfuric and nitric acids, there is no constraint on distal delivery, the nonreabsorbability of the administered anion causing prompt, total delivery of Na+ to exchange sites in quantities equal to administered hydrogen. Thus, with H2SO4 and HNO3 the sole constraint on removal of the acid load is the inability of the distal exchange mechanism to conserve the Na+ increment fully by means of H+ exchange. Escape of Na+ and K+ into the urine and the resulting stimulus to Na(+)-H+ exchange remove this constraint and are responsible for establishment of a new steady-state of acid-base equilibrium at plasma [HCO3-] levels significantly higher than those seen with HCl. The feeding of HCl in the presence of a normal salt intake led to a degree of metabolic acidosis not significantly different from that seen in dogs ingesting a low-salt diet. We suggest that the presence of dietary sodium at distal exchange sites did not enhance acid excretion because it is only after a loss of body sodium stores that sodium avidity is increased sufficiently to allow full removal of the acid load. The present findings indicate that the fundamental factors controlling acid excretion and bicarbonate reabsorption in metabolic acidosis are closely similar to those operative in metabolic alkalosis.

The critical role of the adrenal gland in the renal regulation of acid-base equilibrium during chronic hypotonic expansion. Evidence that chronic hyponatremia is a potent stimulus to aldosterone secretion.

Recent studies have shown that chronic hypotonic volume expansion (HVE) induced by administration of vasopressin and water stimulates distal hydrogen ion secretion and thereby (a) permits dogs with HCl-acidosis to restore acid-base equilibrium to normal despite continued acid feeding and (b) permits normal dogs to conserve filtered bicarbonate quantitatively despite the natriuresis induced by water retention. To examine whether these effects of chronic HVE are mediated by augmented mineralocorticoid secretion, urinary and plasma aldosterone levels were monitored during prolonged administration of vasopressin. In HCl-fed animals, the HVE-induced rise in plasma [HCO3] (from 13.8 to 21.3 meq/liter) was associated with a rise in aldosterone excretion from 0.45 to 0.88 mug/day (P less than 0.02). In normal animals, in which plasma [HCO3] remained stable during HVE (21.9 vs. 20.0 meq/liter), aldosterone excretion rose from 0.51 to 2.28 mug/day (P less than 0.02) and plasma aldosterone concentration rose from 8.1 to 39.8 ng/100 ml (P less than 0.01). Vasopressin and water were also administered to adrenalectomized animals maintained on glucocorticoids and a slightly subphysiologic replacement schedule of mineralocorticoids. In the HCl-fed adrenalectomized group, plasma [HCO3], instead of rising to normal, showed no significant change (16.9 vs. 15.0 meq/liter). In the non-HCl-fed adrenalectomized group, plasma [HCO3], rather than remaining stable, fell significantly (20.3 vs 16.5 meq/liter, P less than 0.1). Two conclusions can be drawn from this study: (a) the well-known inhibitory effect of volume expansion on aldosterone secretion can be overridden by a potent stimulatory effect on the adrenal produced by severe chronic hypotonicity, and (b) the response of plasma [HCO3] observed during severe chronic HVE is mediated by augmented mineralocorticoid secretion. These findings, furthermore, offer a possible explanation for the puzzling observation that plasma [HCO3] in patients with the syndrome of inappropriate antidiuretic hormone secretion is maintained at normal levels even in the face of severe hyponatremia.

The nature of the renal response to chronic disorders of acid-base equilibrium.

The rate of acid excretion by the kidney appears to be determined by factors regulating the site and the rate of sodium reabsorption, rather than by a homeostatic mechanism that responds to systemic pH. This hypothesis, although unconventional, is supported by much experimental evidence, and it accounts for a wide variety of clinical and physiologic findings that heretofore have been difficult or impossible to explain.

Towards the simulation of clinical cognition. Taking a present illness by computer.

Remarkably little is known about the cognitive processes which are employed in the solution of clinical problems. This paucity of information is probably accounted for in large part by the lack of suitable analytic tools for the study of the physician's thought processes. Here we report on the use of the computer as a laboratory for the study of clinical cognition. Our experimental approach has consisted of several elements. First, cognitive insights gained from the study of clinicians' behavior were used to develop a computer program designed to take the present illness of a patient with edema. The program was then tested with a series of prototypical cases, and the present illnesses generated by the computer were compared to those taken by the clinicians in our group. Discrepant behavior on the part of the program was taken as a stimulus for further refinement of the evolving cognitive theory of the present illness. Corresponding refinements were made in the program, and the process of testing and revision was continued until the program's behavior closely resembled that of the clinicians. The advances in computer science that made this effort possible include "goal-directed" programming, pattern-matching and a large associative memory, all of which are products of research in the field known as "artificial intelligence". The information used by the program is organized in a highly connected set of associations which is used to guide such activities as checking the validity of facts, generating and testing hypotheses, and constructing a coherent picture of the patient. As the program pursues its interrelated goals of information gathering and diagnosis, it uses knowledge of diseases and pathophysiology, as well as "common sense", to dynamically assemble many small problem-solving strategies into an integrated history-taking process. We suggest that the present experimental approach will facilitate accomplishment of the long-term goal of disseminating clinical expertise via the computer.

In the pipeline: a wave of valuable medical technology.

Technologic change has proceeded at a rapid pace during the past twenty years, and advances that are even more remarkable are in sight over the next decade. These changes will be driven largely by advances in molecular and cell biology, imaging techniques, and tissue engineering. Therapies directed toward causes rather than consequences of disease could conceivably produce inexpensive cures and thus slow the rise in medical costs. A more likely scenario envisions a continued rise in costs as advances in technology produce many expensive interventions that extend life but are not curative.

Eliminating waste and inefficiency can do little to contain costs.

This study estimates potential savings from eliminating waste and inefficiency in the acute care sector (hospital, physician, and pharmaceutical). Our analysis indicates that in the unlikely event that all potential savings are achieved between 1994 and 2000, the rise in costs would be reduced by about 1.5 percentage points annually. This would slow the real rise in costs from a projected rate of 6.5 percent to 5 percent annually. Covering the uninsured would partially offset these savings and bring the rise in costs to more than 5.5 percent annually. If our estimate of potential efficiency savings is in error by plus or minus 50 percent, the projected rise in costs would be altered by about one percentage point. We conclude that savings from eliminating inefficiency are likely to fall far short of the Clinton administration's cost containment goals.

The effects of aging and population growth on health care costs.

Aging and population growth both contribute importantly to the rise in health care costs. However, the percentage contribution of these factors declined between 1970 and 1990, and we expect a continued decline through 2005. Data indicate that the relative costs of treating patients age sixty-five and over grew more rapidly than did the costs of treating other patients. Sensitivity analyses indicate that regardless of whether these trends persist, the percentage contribution of aging and demography is likely to decline between 1990 and 2005. Application of our model through 2030 suggests that if current trends persist, aging will cause a major acceleration in the rise in costs.

Hospital cost control: a bitter pill to swallow.

Americans delude themselves if they think that the rising tide of medical costs can be stemmed for long without sacrificing some beneficial care. Elimination of waste from the medical system can achieve large savings. But these savings cannot offset for more than a few years the cost-increasing effects of new medical technology and an aging population. Comparing the American experience with the rationing of health care in Britain, these authors conclude that though the differences are substantial between the two countries, the United States may well need to apply similar constraints, and that Americans will no longer be willing to support a system of unlimited medical care.