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Biomedical subjects

J F Butterworth

Publications and source records attributed to J F Butterworth.

At least 37 records · Page 2Linked to original sources
PubMed1995

A pharmacokinetic and pharmacodynamic evaluation of milrinone in adults undergoing cardiac surgery.

Milrinone can reverse acute postischemic myocardial dysfunction after cardiopulmonary bypass, although neither the appropriate bolus dose nor its pharmacokinetics has been established for cardiac surgical patients. Consenting patients undergoing cardiac surgery received milrinone (25, 50, or 75 micrograms/kg) in an open-label, dose-escalating study if their cardiac index was < 3 L.min-1.m-2 after separation from bypass. Heart rate, mean arterial blood pressure, pulmonary capillary wedge pressure, and cardiac index were determined before and after the administration of milrinone. Timed blood samples were obtained for measurement of milrinone plasma concentrations and pharmacokinetic analysis. Twenty-nine of 60 consenting patients had cardiac indices < 3 L.min-1.m-2 after separation from bypass, received milrinone, and completed the protocol. All three bolus doses of milrinone significantly increased cardiac index. The 50- and 75-micrograms/kg doses produced significantly larger increases in cardiac index than the 25-micrograms/kg dose; however, the 75-micrograms/kg dose did not produce a significantly larger increase in cardiac index than did the 50-micrograms/kg dose. Two of 10 patients receiving milrinone 25 micrograms/kg, but no patient receiving either 50 or 75 micrograms/kg, required early epinephrine rescue when the cardiac index failed to increase by > 15%. The 75-micrograms/kg dose was associated with a case of ventricular tachycardia. The three-compartment model better described milrinone drug disposition than the two-compartment model by both visual inspection and Schwartz-Bayesian criterion. There was only limited evidence of dose-dependence, so data from all three doses are reported together (and normalized to the 50-micrograms/kg dose). Data from one patient was discarded (samples mislabeled). Using mixed-effects nonlinear regression (for n = 28), the following volumes were determined for the three compartments: V1 = 11.1 L, V2 = 16.9 L, and V3 = 363 L. Similarly, the following clearances were estimated for the three compartments: Cl1 = 0.067 L/min, Cl2 = 1.05 L/min, and Cl3 = 0.31 L/min. The 50-micrograms/kg loading dose appeared more potent than the 25-micrograms/kg dose, and, as potent, but with possibly fewer side-effects than the 75-micrograms/kg dose. The short context-sensitive half-times of 6.7 or 10.2 min after 1- or 10-min bolus infusions underscore the need for prompt institution of a maintenance infusion when milrinone concentrations must be maintained.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Triiodothyronine increases contractility independent of beta-adrenergic receptors or stimulation of cyclic-3',5'-adenosine monophosphate.

BACKGROUND: Triiodothyronine regulates cardiac contractility; however, the mechanisms by which it produces its acute contractile effects remains unknown. We compared the acute effects of thyroid hormones (triiodothyronine [T3] and thyroxine [T4]) and of isoproterenol on the contractility of isolated rat hearts. In addition, we sought to determine whether the acute inotropic effects of thyroid hormones were mediated by beta-adrenergic receptors or by increased production of cyclic-3',5'-adenosine monophosphate (cAMP). METHODS: A Langendorff heart preparation harvested from euthyroid male Sprague-Dawley rats was used. Drugs were administered through an aortic perfusion catheter. A pressure-transduced left-ventricular balloon catheter measured pressure and heart rate changes. Changes in the maximum positive rate of change in pressure (dP/dT) and maximum negative dP/dT were determined. Responses to varying doses of T3, T4, and isoproterenol were assessed in the presence and absence of beta-adrenergic receptor blockade with propranolol. cAMP production, measured by radioimmunoassay, was determined in myocardial cell suspensions after incubation with T3 or isoproterenol. RESULTS: T3 0.74 nmol rapidly and significantly increased maximum dP/dT by 335 +/- 38 mmHg/s within 30 s after bolus injection; however, contractility was unchanged after as much as 12.9 nmol T4. The maximal increase in dP/dT after 0.8 nmol isoproterenol was comparable to that produced by T3. However, the cardiotonic actions of isoproterenol were significantly slower to develop (peaking at 60 vs. 15 s) and lasted longer than those of T3. Pretreatment with propranolol 1 mumol diminished the contractile effects of isoproterenol but had no effect on those of T3. Concentrations of isoproterenol that increase contractility also significantly increased cAMP production in isolated rat myocardial cells. However, T3 failed to increase cAMP production. CONCLUSIONS: These results demonstrate that the acute inotropic effects of T3 are not shared by T4 and appear unrelated to beta-adrenergic receptor mechanisms or to generation of cAMP. Thus, T3 acutely stimulates cardiac contraction by mechanisms that differ from those of the more commonly used beta-adrenergic receptor agonists and phosphodiesterase inhibitors. Further studies are needed to identify the mechanisms underlying the acute contractile effects of T3 and to determine whether T3 will prove useful for increasing ventricular function in patients.

Adrenergic beta-Antagonists↗
PubMed1995

Calcium entry attenuates adenylyl cyclase activity. A possible mechanism for calcium-induced catecholamine resistance.

In experimental animals, coadministration of calcium (Ca) salts with beta-adrenergic receptor agonists reduces the increased blood pressure and cyclic AMP (cAMP) produced by beta-adrenergic receptor agonists alone. In patients, coadministration of these drugs reduces the increased cardiac output and blood glucose produced by selective administration of beta-adrenergic agonists. The mechanism by which Ca might produce catecholamine resistance remains unclear. Healthy volunteers donated venous blood from which lymphocytes were isolated. The cAMP production was measured by radioimmunoassay under control conditions and after incubation with epinephrine or colforsin (forskolin) in the presence and absence of inhibitors. Epinephrine and colforsin produced concentration-dependent increases in cAMP production. Extracellular Ca concentration over the range from 0 to 8 mM did not inhibit basal cAMP production or that stimulated by either colforsin or epinephrine. The calcium channel agonist Bay K 8644 (50 microM) combined with normal extracellular Ca concentration significantly attenuated colforsin-induced increases in cAMP production. When barium was substituted for Ca in the extracellular fluid, the cAMP response to colforsin was restored, despite Bay K 8644. Inhibition of Ca channel permeability with cadmium or cobalt ions partially restored colforsin-stimulated cAMP production, despite the presence of extracellular Ca and Bay K 8644. These results suggest that entry of Ca ions through Ca channels attenuates adenylyl cyclase. The inhibition appears specific for Ca ions over other permeant divalent cations, and favors a possible physiologic role for the recently cloned Ca-inhibited adenylyl cyclase.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Effect of pH and lidocaine on beta-adrenergic receptor binding. Interaction during resuscitation?

Epinephrine and other beta-adrenergic receptor (beta AR) agonists are often administered during cardiopulmonary resuscitation, a time when acid-base abnormalities and arrhythmias also commonly occur. We tested whether beta 2AR binding is influenced by pH or the antiarrhythmic drug lidocaine, and whether pH might influence the interaction of lidocaine with beta 2ARs. With institutional review board approval and informed consent, 32 venous blood samples were obtained from volunteers. Lymphocytes (which bear beta 2ARs similar to those found in heart) were isolated by density gradient centrifugation. Specific binding of the beta AR ligand 3H-dihydroalprenolol (3H-DHA) was determined with lidocaine concentrations ranging from 10(-6) to 10(-2) mol/L (n = 18 experiments), and with and without lidocaine (n = 10 experiments), 100 mumol/L, and with and without QX314 (a permanently charged lidocaine derivative), 1 mmol/L (n = 4 experiments). Data are presented as percent of control-specific binding measured at a pH of 7.4. Statistical analysis consisted of Spearman's rank-test. 3H-DHA-specific binding increased (p < .001) with pH. Thus, alkaline conditions favored binding of 3H-DHA to the receptor. Lidocaine inhibited 3H-DHA binding to beta 2ARs in a concentration-dependent manner. The concentration that inhibited specific binding of 3H-DHA by 50% was 3.1 x 10(-4) mol/L (95% confidence limits, 1.3 x 10(-4) to 7.5 x 10(-4) mol/L). Lidocaine potency at inhibiting beta 2AR binding also increased with increasing pH; thus, there was limited benefit (in terms of increasing binding to beta 2ARs) to increasing pH when lidocaine was present. QX314, despite being present in a 10-fold greater concentration than lidocaine, had no effect on 3H-DHA binding at any tested pH. The affinity of beta 2 ARs for both 3H-DHA and lidocaine increased with pH. Thus, the response to beta 2AR agonists (when no lidocaine is present) might be expected to be greater with normal or alkalotic pH than under acidotic conditions, supporting the correction of metabolic acidosis to achieve optimal effects from beta 2AR agonists during resuscitation.

Adrenergic beta-Antagonists↗
PubMed1994

Hemodynamic and renal effects of dopexamine and dobutamine in patients with reduced cardiac output following coronary artery bypass grafting.

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.

Adrenergic beta-Antagonists↗
PubMed1993

Bupivacaine inhibits cyclic-3',5'-adenosine monophosphate production. A possible contributing factor to cardiovascular toxicity.

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.

Adenylyl Cyclases↗
PubMed1993

Hemodynamic and pharmacodynamic comparison of doxacurium and pipecuronium with pancuronium during induction of cardiac anesthesia: does the benefit justify the cost?

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)

Anesthesia, Intravenous↗
PubMed1993

Combined inotropic effects of amrinone and epinephrine after cardiopulmonary bypass in humans.

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.

Amrinone↗
PubMed1993

Amrinone in cardiac surgical patients with left-ventricular dysfunction. A prospective, randomized placebo-controlled trial.

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.

Adult↗
PubMed1993

The alpha 2-adrenergic agonists clonidine and guanfacine produce tonic and phasic block of conduction in rat sciatic nerve fibers.

To determine whether alpha 2-adrenergic agonists inhibit impulse conduction, clonidine and guanfacine were applied to rat sciatic nerve fibers studied in vitro. Clonidine and guanfacine produced concentration-dependent, tonic inhibition of compound action potentials in large, myelinated A alpha fibers. The 50% effective concentration (EC50) of clonidine measured 2.0 +/- 0.8 mM (mean +/- standard deviation); the EC50 of guanfacine measured 1.2 +/- 0.2 mM. Clonidine was also less potent than guanfacine at phasic block of A alpha compound action potentials examined at 10 Hz. Both drugs inhibited tonic impulse conduction in C fibers in a concentration-dependent, reversible fashion, and produced greater inhibition of C fiber than A alpha compound action potentials at all drug concentrations. Again, clonidine appeared to inhibit C fiber compound action potentials (EC50 = 0.45 +/- 0.01 mM) with less potency than guanfacine (EC50 = 0.17 +/- 0.06 mM). We conclude that clonidine and guanfacine, unlike traditional local anesthetics, demonstrate a tendency toward steady-state differential nerve block wherein C fibers are blocked to a greater extent than A alpha fibers.

Action Potentials↗
PubMed1993

Pharmacologic cardiovascular support.

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.

Animals↗
PubMed1992

Parathyroid hormone responses to marked hypocalcemia in infants and young children undergoing repair of congenital heart disease.

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.

Blood Proteins↗
PubMed1992

Is calcium or ephedrine superior to placebo for emergence from cardiopulmonary bypass?

To determine whether ephedrine or CaCl2 improves hemodynamics in cardiac surgery patients emerging from cardiopulmonary bypass, three sequential doses of either CaCl2 (200 mg/dose; n = 12), ephedrine (5 mg/dose; n = 12), or placebo (n = 12) were administered in a prospective, randomized, double-blind fashion. Thermodilution volumetric catheters were used to calculate right ventricular (RV) volumes and ejection fraction. The first dose of ephedrine improved RV stroke volume from 57 +/- 3 to 63 +/- 4 mL/beat (P < 0.05) and ejection fraction from 44 +/- 2% to 49 +/- 2% (P < 0.05). Subsequent doses maintained this improvement but without further change. In contrast, placebo and CaCl2 had minimal effects on RV end-systolic volume, stroke volume, and ejection fraction. After the third injection of ephedrine, mean arterial pressure had significantly increased from 78 +/- 2 to 93 +/- 4 mmHg (P < 0.05) in contrast to insignificant increments with placebo and CaCl2. Serum ionized calcium increased by 6% to 8% after each CaCl2 bolus but remained stable in the ephedrine and placebo groups. CaCl2 failed to improve RV performance in mildly hypocalcemic patients during separation from cardiopulmonary bypass. In patients with normal preoperative ventricular function, ephedrine more effectively improved RV performance and arterial blood pressure than placebo or CaCl2, and is a suitable short-acting drug to assist separation from cardiopulmonary bypass.

Adult↗
PubMed1992

Dobutamine increases heart rate more than epinephrine in patients recovering from aortocoronary bypass surgery.

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)

Blood Pressure↗
PubMed1992

A randomized, blinded, placebo-controlled evaluation of calcium chloride and epinephrine for inotropic support after emergence from cardiopulmonary bypass.

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.

Calcium↗