Biomedical subjects
Publications and source records attributed to R C Prielipp.
Neuromuscular blocking drugs are used routinely to facilitate the care of critically ill patients of all ages. This article addresses current uses and concerns about the appropriate administration of these drugs. Several important topics are highlighted, including basic physiology of neuromuscular transmission, blocker pharmacology, drug selection, monitoring, and future areas of research.
Pharmacologic administration of sedatives is used routinely in the care of the critically ill to enhance patient comfort and optimize care. Long-term administration of NMB drugs is far less frequent but often occurs in patients with greater organ dysfunction. The experience of several authors using NMB drugs in the ICU is summarized in Table 5. Both classes of drugs have potential untoward effects. Some are readily predictable; others are not. NMB drugs enjoy a long record of safe, effective use during the perioperative period, but certain issues linger in defining appropriate administration to critically ill patients. Major concerns focus on the appropriate drug selection and delivery, monitoring, and neuromuscular recovery of patients who receive NMB drugs for longer than 24 hours. The development of myopathy and paresis has been increasingly recognized after prolonged use of NMB drugs in the ICU. Further investigation needs to fully characterize this process, identify those at risk, and outline a mechanism to prevent or limit the injury. Prolonged weakness may occur secondary to changes in the basic pharmacology and elimination of NMB drugs in ICU patients. Pathophysiologic changes in the nerve, muscle, or neuromuscular junction may also play a role in the development of some cases of prolonged weakness or myopathy after discontinuation of NMB drugs. Concerns about the potential for direct or indirect toxicity of NMB drugs to skeletal muscle and in the CNS remain. Resolution of these issues will improve the selection and optimal administration of sedative and NMB drugs in the ICU setting.
Unilateral mydriasis is a disturbing finding during anaesthesia and may indicate serious neurological injury. In addition, the assessment of abnormal neurological findings is limited during general anaesthesia, and therefore requires special consideration. I report finding a dilated right pupil (7 mm, nonreactive to light) after bronchoscopic tracheal intubation and induction of general anaesthesia in a frail, 74-yr-old woman with cervical subluxations and spinal cord impingement. The possible aetiology of the unilateral mydriasis includes the effects of anaesthetic agents, stellate ganglion block, impaired venous return from the head and neck, acute intracranial mass lesion or an haemorrhagic event, direct eye trauma, pre-existing medical or surgical conditions, and inadvertent direct deposition of alpha-adrenergic or anticholinergic agents in the eye. Consideration of these factors, the autonomic innervation of the eye, and an intraoperative "wake-up" test allowed satisfactory neurological assessment in this patient and surgery to proceed. Unilateral mydriasis, while unusual, may be seen during general anaesthesia and requires thorough knowledge of autonomic nerve pathways and pharmacology of the eye for correct diagnosis. In this case, mydriasis was considered to result from phenylephrine/lidocaine spray which was used to provide topical anaesthesia to the airway.
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OBJECTIVE: Dopexamine hydrochloride is a novel synthetic adrenergic agonist that combines the renal effects of dopamine with the hemodynamic effects of dobutatmine. Our study is designed to compare the hemodynamic, diuretic, and natriuretic effects of dopexamine and dobutamine in patients with reduced cardiac index following heart surgery. DESIGN: Prospectively randomized, blinded study. SETTING: Operating room and intensive care unit of a large, urban, academic medical center. PATIENTS: Twenty-eight patients undergoing elective coronary artery bypass grafting (CABG) with preoperative ejection fraction of at least 40 percent gave informed consent. The study group consisted of the ten patients who had a cardiac index < or = 2.5 L/min/m2 (while receiving no inotropic medication) immediately after separation from cardiopulmonary bypass. INTERVENTIONS AND MEASUREMENTS: Study patients were randomly given a starting dose of either 5 micrograms/kg/min of dobutamine (n = 5) or 2 micrograms/kg/min of dopexamine (n = 5). During the initial 30 min following separation from bypass, dosages were titrated incrementally to maintain cardiac index > or = 3.0/L/min/m2. Further titrations of the drug were done only if cardiac index fell below 3.0 L/min/m2 or if sustained tachycardia occurred during the 24-h study period. Data were collected at 5- and 10-min intervals for the first 30 min after separation from bypass, hourly for the next 8 h, then every 2 h for the remainder of the study period. RESULTS: Both drugs increased cardiac index by more than 50 percent over baseline (dobutamine 2.2 +/- 0.1 to 3.5 +/- 0.2 [p < 0.05]; dopexamine, 2.3 +/- 0.1 to 3.5 +/- 0.1 [p < 0.05] L/min/m2). The mean dose required to maintain cardiac index > or = 3.0L/min/m2 was 1.5 micrograms/kg/min for dopexamine and 3.5 micrograms/kg/min for dobutamine. There were no significant differences in either urinary output or net sodium excretion in the dopexamine group compared with the dobutamine group, and tachycardia (heart rate > 120 beats/min) was more common in the dopexamine group. CONCLUSIONS: Our study demonstrates that dopexamine produces hemodynamic, diuretic, and natriuretic effects similar to dobutamine in patients with reduced cardiac index following CABG.
While all neuromuscular blocking agents (NMBAs) effectively interrupt neuromuscular transmission, it must be emphasized that these drugs are completely devoid of analgesic, sedative, or amnestic properties. The increasing use of NMBAs in the ICU requires familiarity with their basic pharmacologic properties, as well as an appreciation of potential problems associated with chronic (> 24 hrs) neuromuscular blockade. Although NMBAs possess an impressive safety record, the majority of recommendations for neuromuscular blocker use in the ICU are extrapolated from short-term perioperative studies in healthy patients. NMBAs are structurally related to acetylcholine and their main site of action is the postjunctional nicotinic acetylcholine receptor, although prejunctional interaction may be an important component of total activity. These drugs act to either sustain a depolarization at the postjunctional membrane (succinylcholine), or they inhibit neuromuscular transmission by a competitive (non-depolarizing) blocking mechanism. Adverse hemodynamic consequences may result from concurrent stimulation of muscarinic receptors, autonomic ganglia, histamine, or catecholamine release associated with some agents. The metabolism and excretion of NMBAs may be altered in ICU patients with end-organ dysfunction, concurrent medications, electrolyte, acid-base, and nutritional abnormalities, along with underlying nervous system and muscle pathology. Prolonged weakness after discontinuation of NMBAs is increasingly recognized after these agents are used for extended periods. This phenomenon may be related to alterations in the pharmacokinetics and pharmacodynamics, along with altered physiology of the neuromuscular junction, nervous system, or muscle, or other undefined toxic effects. A sound knowledge of the basic physiology of the neuromuscular junction, neuromuscular blocker pharmacology, and standard techniques to assess the degree of neuromuscular blockade provides the rationale for drug selection when paralysis is indicated in ICU patients.
BACKGROUND: It was hypothesized that local anesthetic inhibition of cyclic-3',5'-adenosine monophosphate (cAMP) production may contribute to cardiovascular toxicity. This study was undertaken to determine whether bupivacaine is a more potent inhibitor of cAMP production than are chemically related local anesthetics that are less prone to produce cardiovascular toxicity. METHODS: Volunteers provided venous blood from which lymphocytes were isolated. Production of cAMP was measured under basal conditions, and in response to stimulation with either forskolin or epinephrine. Inhibition of basal, epinephrine-stimulated, and forskolin-stimulated cAMP production by mepivacaine, ropivacaine, and bupivacaine was assessed. RESULTS: Both forskolin and epinephrine produced concentration-dependent increases in cAMP production; the 50% effective concentrations (EC50S) for these drugs were 3.6 x 10(-8) and 4.6 x 10(-8) M, respectively. Maximal forskolin-stimulated cAMP production (6.6 +/- 0.8 pmol/10(6) [corrected] cells/10 min at 10(-6) M) was greater than maximal epinephrine-stimulated cAMP production (4.2 +/- 0.6 pmol/10(6) [corrected] cells/10 min at 10(-5) M). Bupivacaine (IC50 = 2.3 x 10(-6) M) more potently inhibited basal cAMP production than either ropivacaine (IC50 = 4 x 10(-6) M) or mepivacaine (IC50 = 3.2 x 10(-5) M). Similarly, bupivacaine (IC50 = 2.3 x 10(-6) M) was as potent as ropivacaine (IC50 = 1.7 x 10(-6) M) and more potent than mepivacaine (IC50 = 8.9 x 10(-6) M) at inhibiting epinephrine-stimulated cAMP production. Bupivacaine (IC50 = 5.3 x 10(-6) M) was only marginally more potent than ropivacaine (IC50 = 9.7 x 10(-6) M) or mepivacaine (IC50 = 6.8 x 10(-6) M) at inhibition of forskolin-stimulated cAMP production. Comparison of epinephrine concentration-response curves in the presence and absence of bupivacaine (0.35, 3.5, and 35 microM) demonstrated noncompetitive inhibition of cAMP production by the local anesthetic. CONCLUSIONS: Inhibition of basal and epinephrine-stimulated cAMP production may contribute to local anesthetic cardiovascular toxicity. Inhibition of cAMP production may limit the success of resuscitative measures and drugs administered for bupivacaine cardiovascular toxicity. Increasing the resuscitation dose of epinephrine may be required to restore cardiac contractile function after bupivacaine intoxication.
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We compared the pharmacodynamic effects and hospital costs of three long-acting neuromuscular blocking drugs in a prospective, randomized, double-blind manner. Each neuromuscular blocking drug was administered with fentanyl (50 micrograms/kg) for intravenous induction of anesthesia for coronary artery bypass surgery. Each patient received twice the 95% effective dose (ED95) of either pancuronium (0.14 mg/kg, n = 10), pipecuronium (0.10 mg/kg, n = 10), or doxacurium (0.05 mg/kg, n = 10). Hemodynamic measurements were recorded at baseline, 5 min after completion of anesthetic induction, immediately after endotracheal intubation, and 5 min after intubation. Only small hemodynamic differences between neuromuscular blocking drugs were observed. Doxacurium (but not pancuronium or pipecuronium) significantly decreased mean arterial blood pressure (from 94 +/- 4 mm Hg before induction to 83 +/- 3 mm Hg 5 min after intubation); nevertheless, there were no significant between-group differences at any time. Pancuronium increased heart rate (from 68 +/- 4 beats/min before induction to 76 +/- 5 beats/min 5 min after intubation); however, pancuronium differed significantly from doxacurium and pipecuronium only 5 min after induction and 5 min after intubation. Central venous pressure, pulmonary artery occlusion pressure, cardiac index, and systemic and pulmonary vascular resistance indices did not change. Electrocardiographic abnormalities were observed in two pipecuronium patients: ST segment depression in one and premature ventricular contractions in another. No other electrocardiographic changes were observed. There were no significant between-group differences in the need for hemodynamic interventions.(ABSTRACT TRUNCATED AT 250 WORDS)
Amrinone, a phosphodiesterase inhibitor, and epinephrine, an alpha- and beta-adrenergic receptor agonist, are inotropic drugs used during cardiac surgery to reverse myocardial depression after cardiopulmonary bypass. However, these drugs have not been compared separately, or in combination, in this patient population. We hypothesized that the combination might have complementary actions in improving myocardial function. We, therefore, compared amrinone, epinephrine, and the combination of amrinone and epinephrine in a randomized, blinded, placebo-controlled study in patients undergoing coronary artery bypass grafting. Forty patients with ejection fractions > 0.45 were studied. Right ventricular ejection fraction pulmonary artery catheters and radial arterial catheters were inserted before fentanyl-midazolam anesthesia. After separation from bypass, patients received either a placebo (n = 20) or amrinone bolus (1.5 mg/kg, n = 20) at time 0 and a placebo (n = 20) or epinephrine (30 ng.kg-1.min-1, n = 20) infusion at time 5 min. This resulted in four study groups, n = 10 in each group. Data were collected every 2.5 min for 10 min. Epinephrine, amrinone, and the combination of both drugs significantly increased cardiac output, stroke volume, O2 delivery, and left ventricular stroke work. The increase in stroke volume (P < 0.05) was 12 +/- 6, 16 +/- 4, and 30 +/- 4 mL/beat with epinephrine, amrinone, and the combination of amrinone and epinephrine, respectively. The amrinone-epinephrine combination increased stroke volume as much as the sum of amrinone and epinephrine given separately. Systemic vascular resistance and pulmonary vascular resistance decreased with amrinone and amrinone-epinephrine, but not with epinephrine. Epinephrine increased mean arterial and mean pulmonary arterial pressures. Right ventricular ejection fraction did not significantly increase (P = 0.09) with epinephrine, but increased significantly with amrinone (0.45 to 0.53, P = 0.01), and with the combination (0.43 to 0.55, P = 0.006). These data indicate that amrinone and epinephrine effectively increase myocardial performance during cardiac surgery. Right ventricular function especially was improved with amrinone and the combination of amrinone and epinephrine. The combined effects of amrinone and epinephrine may be useful in patients recovering from the ischemia and reperfusion injury resulting from coronary artery bypass grafting.
STUDY OBJECTIVE: To evaluate the efficacy of amrinone for facilitating weaning from cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized, double-blind, placebo-controlled trial with epinephrine as "rescue" therapy. SETTING: Operating room of a large, metropolitan tertiary-care center. PATIENTS: Thirty-nine patients with preoperative left ventricular dysfunction undergoing cardiac surgery. Thirty-three patients underwent aortocoronary bypass grafting; six patients underwent valve replacement for severe mitral or aortic regurgitation. INTERVENTIONS: Patients received either amrinone (1.5 mg/kg loading dose plus 10 micrograms/kg/min maintenance infusion; n = 20) or placebo (n = 19) in a randomized double-blind fashion shortly (median, 10.5 min; range, 2 to 24 min) before separation from CPB. Inotropic drugs (other than the study drug) were withheld prior to separation from CPB unless safety considerations demanded that the protocol be broken. Patients who could not be weaned from CPB, as well as those with a cardiac index of 2.2 L/min/m2 or less after weaning from CPB, received epinephrine (60 to 120 ng/kg/min) by infusion. MEASUREMENTS AND RESULTS: Fourteen of 19 patients receiving placebo but only 1 of the 20 patients receiving amrinone (p = 0.00001) required epinephrine infusion to separate from bypass. The cardiac index of 4 patients receiving placebo (but no patients with amrinone) failed to exceed 2.2 L/min/m2 despite epinephrine infusion, requiring the protocol to be broken (p < 0.08). Blood concentrations of amrinone determined (only in the amrinone group) after separation from CPB confirmed that the dosage of amrinone produced an effective blood concentration. Fourteen of 19 patients receiving placebo and 17 of 20 patients receiving amrinone required an infusion of phenylephrine titrated to maintain systolic blood pressure less than 90 mm Hg. Seven patients (four with amrinone and three with placebo) required antiarrhythmic drug therapy. The outcome at 3 months was similar in the 2 groups. CONCLUSIONS: Amrinone by itself is an effective agent to facilitate weaning from CPB, and therapy with amrinone reduced the need for individualized titration of epinephrine. Amrinone is as effective as individualized titration of epinephrine (after CPB) to improve cardiac function. Patients in the group receiving amrinone had no greater need for vasoconstricting agents than did patients in the group receiving placebo; however, proactive administration of amrinone before separation from CPB appears to offer no greater benefit to high-risk patients than selective administration of drugs (epinephrine) only to those patients who demonstrate the need for drug support at the time of weaning.
The availability of newer and better inotropic agents has led to their widespread application in critically ill medical and surgical patients. Although the elective use of inotropic drugs has been associated with adverse outcomes in patients with cardiomyopathy and chronic heart failure, inotropic drugs used as part of treatment protocols designed to optimize oxygen delivery to tissues have been shown to improve outcome in critical illness. Future research must be aimed toward better definition of clinical settings in which outcome can be improved with inotropes and toward identifying safer agents with fewer adverse side effects.
OBJECTIVES: The integrity of the parathyroid axis was tested in 18 infants and young children undergoing repair of congenital heart disease with cardiopulmonary bypass. BACKGROUND: Infants are believed to have an immature parathyroid hormone response to hypocalcemia. Whereas adults are known to respond appropriately to hypocalcemia during cardiopulmonary bypass, children have not been studied carefully. METHODS: Calcium, magnesium, parathyroid hormone, phosphate and total protein were measured in blood samples withdrawn at defined times before, during and after cardiopulmonary bypass. RESULTS: At the initiation of cardiopulmonary bypass, ionized calcium decreased markedly in 12 infants less than or equal to 24 months old (mean +/- SEM 1.11 +/- 0.04 to 0.29 +/- 0.05 mM) and decreased significantly in 6 young children greater than 24 months old (1.19 +/- 0.02 to 0.42 +/- 0.12 mM). In response to hypocalcemia, parathyroid hormone concentration increased significantly in both the infants (from 42 +/- 8 to 103 +/- 29 and 85 +/- 22 pg/ml) and the young children (from 39 +/- 8 to 44 +/- 20 and 92 +/- 30 pg/ml). Before separation from cardiopulmonary bypass, increased parathyroid hormone concentration restored ionized calcium concentration to 0.75 +/- 0.03 mM in the infants and to 0.92 +/- 0.07 mM in the young children. There was no significant influence of either age or the use of deep hypothermia and circulatory arrest on either calcium or parathyroid hormone responses. Total magnesium and total protein concentrations decreased on initiation of cardiopulmonary bypass and thereafter remained stable. Phosphate concentrations were unchanged during the study. CONCLUSIONS: In infants and young children undergoing cardiac surgery, the parathyroid hormone response to both hypocalcemia and to rising ionized calcium concentrations was at least as great as that of adults. Thus, the calcium-parathyroid-vitamin D axis functions in infants and young children as it does in adults.
To determine whether epinephrine might prove to be a cost-effective substitute for dobutamine, two 8-minute infusions of either epinephrine (10 and 30 ng/kg/min, n = 28) or dobutamine (2.5 and 5 micrograms/kg/min, n = 24) were administered to 52 patients recovering in the intensive care unit (ICU) after aortocoronary bypass (CABG) surgery. At the higher dose, both drugs significantly (P < .05) increased cardiac index (CI), epinephrine from 2.8 +/- 0.1 at baseline to 3.3 +/- 0.1 L/min/m2, and dobutamine from 3.2 +/- 0.1 at baseline to 4.1 +/- 0.2 L/min/m2. Epinephrine increased CI significantly less than dobutamine. Both drugs significantly increased stroke volume index (SVI), epinephrine from 32 +/- 1 at baseline to 36 +/- 1 mL/beat/m2, and dobutamine from 36 +/- 1 at baseline to 40 +/- 2 mL/beat/m2. At the higher dose, the effects of the two drugs on SVI were indistinguishable. On the other hand, while the higher dose of both drugs significantly increased heart rate (HR), epinephrine from 88 +/- 2 at baseline to 90 +/- 2 beats/min and dobutamine from 89 +/- 2 at baseline to 105 +/- 3 beats/min, the increase following the higher dose of dobutamine was significantly greater than that seen after epinephrine. Effects of the two drugs on mean arterial pressure, central venous pressure, pulmonary artery occlusion pressure, systemic vascular resistance, pulmonary vascular resistance, and left-ventricular stroke work did not significantly differ. Similar results were obtained in the subset of patients with baseline CI less than 3 L/min/m2 who more closely resembled patients who might acutely require inotropic drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Forty hemodynamically stable patients were randomized to receive an intravenous bolus of either calcium chloride (5 mg/kg) (n = 20) or placebo (n = 20) (phase I). Six minutes later, they received either an epinephrine (30 ng.kg-1.min-1) (n = 20) or placebo (n = 20) infusion (phase II). Hemodynamic and ionized calcium measurements were obtained in phase I at baseline and at 3 and 6 min after the bolus, and in phase II, at 3 and 6 min (study times 9 and 12 min) after initiation of the infusion. Compared with placebo, calcium did not significantly increase cardiac index but significantly increased mean arterial pressure. Calcium improved cardiac index from 2.46 +/- 0.12 (mean +/- SEM) to 2.74 +/- 0.12 L.min-1.m-2; likewise, placebo improved cardiac index from 2.51 +/- 0.15 to 2.74 +/- 0.15 L.min-1.m-2. Mean arterial blood pressure increased with calcium from 74 +/- 2 to 82 +/- 3 mm Hg compared with a placebo change of 74 +/- 2 to 76 +/- 2 mm Hg. Patients who received the epinephrine infusion (n = 20) demonstrated a significant increase in cardiac index at time 12 min compared with patients receiving only placebo (n = 20). Cardiac index of the epinephrine group increased from 2.56 +/- 0.15 to 2.92 +/- 0.22 L.min-1.m-2, whereas in the placebo group it decreased from 2.86 +/- 0.13 to 2.78 +/- 0.12 L.min-1.m-2. Prior administration of calcium did not alter the subsequent response to epinephrine (n = 10) compared with patients receiving epinephrine alone (n = 10). We conclude that cardiac index improves with time without drug therapy after bypass. Calcium chloride increases mean arterial blood pressure but not cardiac index immediately after cardiopulmonary bypass, whereas low-dose epinephrine significantly increases both cardiac index and mean arterial blood pressure without causing tachycardia in these patients. Calcium chloride (5 mg/kg) did not augment or inhibit the hemodynamic response to an epinephrine infusion.
To contrast the effect of increasing blood calcium concentrations on the cardiovascular actions of intravenous beta-adrenergic agonists and phosphodiesterase inhibitors, 46 patients recovering from aortocoronary bypass surgery received either dobutamine or amrinone both in the presence and absence of a calcium infusion. Cardiac output, systemic arterial pressure, pulmonary arterial pressure, central venous pressure, pulmonary artery occlusion pressure, heart rate, and blood ionized calcium concentration were measured before and during infusions of dobutamine (2.5 and 5.0 micrograms/kg/min) and amrinone (0.75 mg/kg bolus + 10 micrograms/kg/min or 2.25 mg/kg bolus + 20 micrograms/kg/min). After the initial dobutamine infusion period, patients were randomly and blindly assigned to receive either a calcium or placebo infusion, and the dobutamine infusions were repeated. Because of the long duration of amrinone's actions, the amrinone maintenance infusion was continued while randomized, blinded infusion of either calcium or placebo was added. Dobutamine (5 micrograms/kg/min) increased cardiac output from 7.1 +/- 0.3 L/min to 9.1 +/- 0.4 L/min, and increased heart rate from 93 +/- 4 beats/min to 107 +/- 4 beats/min. Systemic vascular resistance decreased and stroke volume increased. Dobutamine had no significant effects on other hemodynamic values. Amrinone (2.25 mg/kg bolus + 20 micrograms/kg/min) increased cardiac output from 5.6 +/- 0.4 L/min to 6.9 +/- 0.5 L/min, and increased heart rate from 87 +/- 3 beats/min to 98 +/- 3 beats/min. Amrinone decreased mean arterial pressure, systemic vascular resistance, pulmonary artery occlusion pressure, central venous pressure, and pulmonary artery pressure. Calcium infusion increased arterial pressure (8 to 13 percent) but had no significant effects on any other hemodynamic parameters. Calcium reduced the increase in cardiac output produced by dobutamine by 30 percent, but it did not alter the cardiotonic actions of amrinone. Thus, calcium inhibits the cardiotonic actions of certain beta-adrenergic agonists, most likely by interfering with signal transduction through the beta-adrenergic receptor complex.
Intravenous magnesium supplementation is often used to control cardiac arrhythmias and coronary artery vasospasm resulting from disturbances of magnesium homeostasis after coronary artery bypass surgery. Many such patients also require inotropic drug support of depressed myocardial function. However, increased serum magnesium concentrations directly depress cardiac contractility in animals and may interfere with catecholamine actions. To determine whether small intravenous doses of magnesium sulfate (MgSO4) interfere with the cardiotonic actions of epinephrine, we examined the hemodynamic effects of MgSO4 and epinephrine infusion in 17 cardiac surgical patients on their 1st postoperative day in a prospective, controlled study. In 11 patients, infusion of MgSO4 (7-mg.kg-1 bolus followed by 10 mg.kg-1.h-1 as a continuous infusion) increased serum magnesium concentrations by 44% (mean +/- standard error of the mean [SEM] of 0.8 +/- 0.1 to 1.2 +/- 0.1 mM; P less than 0.01) but had no significant effect on heart rate; mean arterial, central venous, or pulmonary arterial occlusion pressures; or cardiac output. Epinephrine infusion (30 ng.kg-1.min-1) significantly increased cardiac index (2.7 +/- 0.1 to 3.1 +/- 0.21.min-1.m-2; P less than 0.05); this effect was not altered by MgSO4 administration (n = 11). However, MgSO4 significantly blunted epinephrine's hypertensive action and prevented a significant increase in mean arterial pressure during concurrent MgSO4-epinephrine administration. Six placebo control patients were given two sequential infusions of epinephrine separated by a placebo infusion to rule out an effect of time on the hemodynamic response to epinephrine. Mean arterial pressure and cardiac index responses to epinephrine were identical before and after placebo infusion.(ABSTRACT TRUNCATED AT 250 WORDS)