The impact of longer-than-average anesthesia times on the billing of academic anesthesiology departments.

UNLABELLED: Academic anesthesiology departments provide clinical services for surgical procedures that have longer-than-average surgical times and correspondingly increased anesthesia times. We examined the financial impact of these longer times in three ways: 1) the estimated loss in revenue if billing were done on a flat-fee system by using industry-averaged anesthesia times; 2) the estimation of incremental operating room (OR) sites necessitated by longer anesthesia times; and 3) the estimated potential gain in billed units if the hours of productivity of current anesthesia time were applied to surgical cases of average duration. Health Care Financing Administration average times per anesthesia procedure code were used as industry averages. Billing data were collected from four academic anesthesiology departments for 1 yr. Each claim billed with ASA units was included except for obstetric anesthesia care. All clinical sites that do not bill with ASA units were excluded. Base units were determined for each anesthesia procedure code. The mean commercial conversion factor (US$45 per ASA unit) for reimbursement was used to estimate the impact in dollar amounts. In all four groups, anesthesia times exceeded the Health Care Financing Administration average. The loss per group in billed ASA units if a flat-fee billing system were used ranged from 18,194 to 31,079 units per group, representing a 5% to 15% decrease (estimated billing decrease of US$818,719 to US$1,398,536 per group). The number of excess OR sites necessitated by longer surgical and anesthesia times ranged from 1.95 to 4.57 OR sites per group. The potential gain in billed units if the hours of productivity of current anesthesia time were applied to surgical cases of average duration was estimated to be from 13,273 to 21,368 ASA units. Longer-than-average anesthesia and surgical times result in extra hours or additional OR sites to be staffed and loss of potential reimbursement for the four academic anesthesiology departments. A flat-fee system would adversely affect academic anesthesiology departments. IMPLICATIONS: We examined the economic impact of longer-than-average anesthesia times on four academic anesthesiology departments in three ways: the estimated loss in revenue under a flat-fee system, the excess operating room sites staffed, and the potential gain in revenue if the surgeries were of average length. These results should be considered both in productivity measurements and strategies for operating room management.

[Propofol suppresses sympathetic activity and inhibits the baroreceptor reflex in waking rats]. / Propofol podavliaet simpaticheskuiu aktivnost' i ingibiruet baroretseptornyi refleks u bodrstvuiushchikh krys.

The effects of propofol on sympathetic nerve activity and on the baroreceptor reflexes were examined in male Wistar rats. Sympathetic nerve activity was recorded directly from a renal nerve electrode placed earlier; baroreceptor reflex activity was estimated by changes in blood pressure (BP) and heart rate (HR) induced by the vasopressor phenylephrine, or the vasodilator, nitroprusside. Awake animals were anesthetized with propofol (10 mg/kg iv bolus, followed by approximately 35 mg/kg/hr by infusion) for 30 min. During the first 3 minutes, propofol increased sympathetic nerve activity by 113%, while mean arterial pressure was lowered to 85% of control. After 20 minutes, both sympathetic nerve activity and blood pressure had declined by 14% below baseline. Heart rate was stable at the level of approximately 110% throughout. Propofol also attenuated the sensitivity of chronotropic and sympathetic components of the baroreceptor reflex (i.e., to 23-43% and 25-34%, respectively). Thus, propofol lowers blood pressure by a central mechanism attenuating sympathetic nerve activity and sensitivity of baroreceptor reflex.

Exercise and neuromodulators: choline and acetylcholine in marathon runners.

Certain neurotransmitters (i.e., acetylcholine, catecholamines, and serotonin) are formed from dietary constituents (i.e., choline, tyrosine and tryptophan). Changing the consumption of these precursors alters release of their respective neurotransmitter products. The neurotransmitter acetylcholine is released from the neuromuscular junction and from brain. It is formed from choline, a common constituent in fish, liver, and eggs. Choline is also incorporated into cell membranes; membranes may likewise serve as an alternative choline source for acetylcholine synthesis. In trained athletes, running a 26 km marathon reduced plasma choline by approximately 40%, from 14.1 to 8.4 uM. Changes of similar magnitude have been shown to reduce acetylcholine release from the neuromuscular junction in vivo. Thus, the reductions in plasma choline associated with strenuous exercise may reduce acetylcholine release, and could thereby affect endurance or performance.

Effects of running the Boston marathon on plasma concentrations of large neutral amino acids.

Plasma large neutral amino acid concentrations were measured in thirty-seven subjects before and after completing the Boston Marathon. Concentrations of tyrosine, phenylalanine, and methionine increased, as did their "plasma ratios" (i.e., the ratio of each amino acid's concentration to the summed plasma concentrations of the other large neutral amino acids which compete with it for brain uptake). No changes were noted in the plasma concentrations of tryptophan, leucine, isoleucine, nor valine; however, the "plasma ratios" of acid patterns may influence neurotransmitter synthesis.

Endogenous adenosine and hemorrhagic shock: effects of caffeine administration or caffeine withdrawal.

Plasma adenosine concentrations doubled when rats were subjected to 90 min of profound hemorrhagic shock. Administration of caffeine (20 mg per kg of body weight), an adenosine-receptor antagonist, attenuated the hemorrhage-induced decrease in blood pressure. In contrast, chronic caffeine consumption (0.1% in drinking water), followed by a brief period of caffeine withdrawal, amplified the hypotensive response to hemorrhage. These data suggest that endogenous adenosine participates in the hypotensive response to hemorrhage and that caffeine may protect against, and caffeine withdrawal may exacerbate, this response.

Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma.

Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, we examined the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial [3H]tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of [3H]tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

Spinal cord noradrenergic neurons are activated in hypotension.

Although norepinephrine-containing nerve terminals in the spinal cord synapse in the vicinity of sympathetic preganglionic cells, their effect on sympathetic outflow has remained unclear. Since survival during hypotension necessitates sustaining maximal sympathetic activity, we used experimental hypotension as a physiological stimulus to determine whether such activity is associated with an increase or a decrease in spinal cord norepinephrine turnover. Male Sprague-Dawley rats (500 g) were anesthetized with chloralose and urethane and their left carotid arteries were cannulated for blood pressure measurements and blood removal. Control animals remained normotensive during the 1-h study period; hypotensive animals were bled to a 50 mm Hg systolic pressure. Catecholamine release, as indicated by methoxyhydroxyphenylethyleneglycol sulfate (MHPG-SO4) concentrations, was greater in spinal cords of hypotensive rats than in normotensive controls. Apparent catecholamine synthesis also increased: norepinephrine concentrations did not change even though those of MHPG-SO4 doubled and the accumulation of dihydroxyphenylalanine (in other animals pretreated with NSD 1015) also doubled. These studies show that catecholamine-containing neurons in the spinal cord are stimulated in hypotension, and suggest that they may function physiologically to increase sympathetic outflow and thus blood pressure.

Tyrosine accelerates catecholamine synthesis in hemorrhaged hypotensive rats.

Tyrosine, the amino acid precursor of catecholamines, increases blood pressure (BP) in rats made hypotensive by hemorrhage. Since this amino acid also accelerates catecholamine synthesis in and release from frequently-firing neurons, we tested the hypothesis that tyrosine's pressor action resulted from this mechanism. Male Sprague-Dawley rats (500 g) were anesthetized with chloralose (50 mg/kg) and urethane (500 mg/kg) and tracheostomized. The carotid artery was cannulated allowing BP to be recorded continuously. Blood was removed until systolic BP fell to half of each animal's starting value; 45 min later, animals received tyrosine or other treatments in volumes of 1 ml/kg. Tyrosine (100 mg/kg) increased BP by 58%, while saline caused an insignificant increase. Pretreatment with carbidopa, which inhibits tyrosine's conversion to catecholamines, blocked the amino acid's effect. Tyrosine also failed to increase BP in rats made hypotensive with phentolamine, suggesting that it acts via catecholamine receptors. Adrenal epinephrine significantly (P less than 0.02) and splenic norepinephrine slightly (P less than 0.07) increased in rats receiving tyrosine after 1 h of hypotension when compared with tissue-catecholamine contents in similar rats. These observations show that tyrosine increases BP during hemorrhagic hypotension by accelerating catecholamine synthesis.

Tyrosine's pressor effect in hypotensive rats is not mediated by tyramine.

Tyrosine, the amino acid precursor of catecholamines, increases blood pressure (BP) in hemorrhaged hypotensive rats. Since tyrosine may also be decarboxylated to form tyramine, which releases norepinephrine from sympathetic terminals, we tested the hypothesis that tyramine formation might mediate tyrosine's ability to increase BP. Three lines of evidence indicate that tyrosine does not act via this mechanism: pretreatment with reserpine blocked tyramine's but not tyrosine's pressor activity; pretreatment with hexamethonium left tyramine's effect intact but blocked the pressor response to tyrosine; and plasma tyramine did not increase after an hemodynamically-active dose of tyrosine (100 mg/kg).

Chronic caffeine consumption potentiates the hypotensive action of circulating adenosine.

Mean arterial blood pressure was correlated with arterial plasma adenosine levels during intravenous adenosine infusion in unanesthetized, unrestrained rats. Elevation of plasma adenosine to 5 to 6 microM (normal range 1.6 to 4.6 microM) depressed mean arterial pressure by 20 to 30 percent: this was blocked by a single caffeine injection (15 mg/kg). In contrast, caffeine consumption for 3 weeks, followed by a 1-day washout, markedly potentiated responses to adenosine, plasma levels in the 2 to 4 microM range causing 30 to 40 percent reductions in mean arterial pressure. These observations suggest that chronic occupancy of cardiovascular adenosine receptors by caffeine can enhance tissue responsiveness to adenosine, and that endogenous adenosine might act as a circulating hormone.

Tyrosine's vasoactive effect in the dog shock model depends on the animal's starting blood pressure.

We examined the effect of tyrosine (10-200 mg/kg given intravenously) or placebo on blood pressure (BP) in dogs made hypotensive (systolic BP = 50 mm Hg) by bleeding one hour previously. Animals which, prior to induction of hypotension, had been normotensive (mean arterial pressures, [MAP] less than or equal to 145 mm Hg) subsequently exhibited a dose-related increase in BP after tyrosine administration. In contrast, dogs which had been hypertensive prior to bleeding exhibited a fall in BP after tyrosine. These observations indicated that prior cardiovascular status may be an important factor influencing responses to exogenous tyrosine, and to endogenous catecholamines produced from the tyrosine.

Neurotransmitter precursors and brain function.

Brain function can be affected by the availability of dietary precursors of neurotransmitters. This occurs because the rate-limiting synthetic enzymes are not "saturated" with substrate under normal circumstances. Tyrosine affects catecholaminergic neurons that fire rapidly, whether in the brain stem to decrease blood pressure in hypertension or in the adrenal gland to increase blood pressure in hypotension, and has been used in the treatment of Parkinson's disease and depression. Choline forms acetylcholine and has been used successfully in the treatment of tardive dyskinesia and memory disorders. Tryptophan, which forms serotonin, has been used for chronic pain therapy, sleep disorders, depression, and appetite control. Although these substances may lack the potency of traditionally used agonists, they offer an increase in specificity because the enzymes necessary to convert them to neurotransmitters are found only in neurons. Precursors are also "physiological"; they are consumed as foods and, therefore, should be relatively safe therapeutic agents.

Tyrosine increases blood pressure in hypotensive rats.

Administration of tyrosine, the amino acid precursor of catecholamines, increased blood pressure 38 to 49 percent in rats made acutely hypotensive by hemorrhage; other large neutral amino acids were ineffective. Tyrosine's effect was abolished by adrenalectomy, suggesting that, in hypotensive animals, it acts by accelerating the peripheral synthesis and release of catecholamines.

Phenformin and hyperamylasemia in lactic acidosis.

All cases of lactic acidosis occurring during a 23-month period in a metropolitan teaching hospital were reviewed to ascertain the frequency of hyperamylasemia. Serum amylase activity had been measured in 12 of 26 patients and was elevated in eight (67%). Hyperamylasemia was not significantly more frequent in patients with phenformin-associated lactic acidosis than in patients with lactic acidosis who had not received phenformin. Serum amylase activity did not correlate with the severity of acidosis (arterial pH) or with renal function (serum creatinine).

Serum phenformin concentrations in patients with phenformin-associated lactic acidosis.

Phenformin concentrations were measured in serum from seven patients with phenformin-associated lactic acidosis, and initial values ranging from 20 to 625 ng./ml. were obtained. Five of the seven patients had serum concentrations within the usual therapeutic range of up to 241 ng./ml. Serum phenformin concentrations were measured serially, and apparent half-lives of 5, 25, and 30 hours were obtained in three patients with serum creatinine concentrations of 1.7, 7.6, and 6.0 mg./dl., respectively. Although the half-life of phenformin was prolonged in azotemic patients, no correlation between serum creatinine concentration and serum phenformin could be demonstrated; furthermore, the severity of lactic acidosis as measured by arterial pH and lactate concentration did not correlate with the serum creatinine concentration.