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2.
Anesth Analg ; 93(1): 45-52, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11429337

ABSTRACT

UNLABELLED: Dopamine has a wide spectrum of receptor and pharmacologic actions that may affect cerebral blood flow (CBF). A new, selective dopamine-1 agonist, fenoldopam, is a potent systemic vasodilator with moderate alpha(2)-receptor affinity. However, the effects of fenoldopam on the cerebral circulation are undefined. We therefore hypothesized that infusion of fenoldopam would decrease mean arterial blood pressure (MAP) and might concurrently decrease CBF via vascular alpha(2)-adrenoreceptor activation in awake volunteers. We studied nine healthy normotensive subjects, using positron emission tomography to measure CBF in multiple cortical and subcortical regions of interest. In addition, bioimpedance cardiac output and middle cerebral artery blood flow velocity were determined during fenoldopam-induced hypotension. Three men and four women, aged 25-43 yr, completed the study. Fenoldopam infused at 1.3 +/- 0.4 microg. kg(-1). min(-1) (mean +/- SD) reduced MAP 16% from baseline: from 94 (89-100) mm Hg (mean [95% confidence interval]) to 79 [74-85] mm Hg (P < 0.0001). During the fenoldopam infusion, both cardiac output (+39%), and heart rate (+45%) increased significantly, whereas global CBF decreased from baseline, 45.6 [35.6-58.5] mL. 100 g(-1). min(-1), to 37.7 [33.9-42.0] mL. 100 g(-1). min(-1) (P < 0.0001). Despite restoration of baseline MAP with a concurrent infusion of phenylephrine, global CBF remained decreased relative to baseline values at 37.9 [34.0-42.3] mL. 100 gm(-1). min(-1) (P < 0.0001). Changes in middle cerebral artery velocity did not correlate with positron emission tomography-measured changes of CBF induced by fenoldopam, with or without concurrent phenylephrine. IMPLICATIONS: In awake volunteers with (presumably) intact cerebral autoregulation,fenoldopam-induced hypotension significantly decreased global cerebral bloodflow (CBF). Clinicians should be aware of these pharmacodynamic effects when choosing a vasodilator to control blood pressure, especially in situations where control of CBF, cerebral blood volume, and intracranial pressure are therapeutic priorities.


Subject(s)
Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Cerebrovascular Circulation/drug effects , Dopamine Agonists/pharmacology , Fenoldopam/pharmacology , Adolescent , Adult , Brain/diagnostic imaging , Cardiac Output/drug effects , Depression, Chemical , Female , Heart Rate/drug effects , Humans , Male , Middle Aged , Receptors, Adrenergic, alpha-2/drug effects , Receptors, Dopamine D1/drug effects , Tomography, Emission-Computed , Ultrasonography, Doppler, Transcranial
3.
Anesth Analg ; 92(6): 1384-90, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11375809

ABSTRACT

Epsilon-aminocaproic acid (epsilon-ACA) is administered to cardiac surgery patients to reduce blood transfusions. Highly water-soluble drugs, such as epsilon-ACA, often have larger distribution volumes in males than in females. We hypothesized that epsilon-ACA concentrations using this dosing scheme would differ by gender because of differences in body composition and weight-adjusted volumes of distribution. Ten men and 10 women undergoing elective coronary artery surgery with cardiopulmonary bypass (CPB) received a 50 mg/kg epsilon-ACA initial dose over 20 min and a 25 mg. kg(-1) x h(-1) epsilon-ACA maintenance infusion for 4 h. The area under the epsilon-ACA arterial concentration versus time curves was compared by using analysis of variance. Measured epsilon-ACA concentrations were smaller than predicted by the published model, but the area under the concentration versus time curves was not significantly different between men and women. Combining the present concentration data with that previously published, our updated two-compartment model included the following estimated population pharmacokinetic values: V(1) (11.8 L pre-CPB, 14.9 L during and after CPB), V(2) (12.0 L pre-CPB, 15.0 L during and after CPB), Cl(1) (0.125 L/min pre-CPB, 0.037 L/min during CPB, 0.156 L/min after CPB), Cl(2) (0.155 L/min pre-CPB, 0.013 L/min during CPB, 0.193 L/min after CPB).


Subject(s)
Aminocaproic Acid/pharmacokinetics , Antifibrinolytic Agents/pharmacokinetics , Cardiopulmonary Bypass , Aged , Analysis of Variance , Area Under Curve , Female , Humans , Male , Middle Aged , Sex Characteristics
4.
Crit Care Clin ; 17(4): 843-62, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11762264

ABSTRACT

The effects of BZ drugs result from interaction at the GABAA receptor within the CNS, producing anxiolysis, hypnosis, and amnesia in a dose-dependent fashion. These sedative effects are best titrated to reproducible clinical endpoints, using scoring systems such as the Ramsay scale. All BZs exhibit similar pharmacologic effects, but the important differences in pharmacokinetics and pharmacodynamics should be recognized to use these drugs safely and effectively within the ICU. Diazepam is the classic anxiolytic, amnestic, and sedative agent, but the presence of long-acting active metabolites that depend on the kidneys for elimination limits its use in many ICU patients. Lorazepam is the most potent BZ used in the ICU; it has stable pharmacokinetics and relatively low cost. This drug is best reserved for situations in which rapid onset is not essential and long-term sedation is anticipated. Midazolam has the shortest t1/2 of the commonly used BZs, generates few active metabolites, and is water soluble at physiologic pH. Thus, it is well suited for continuous infusion in the ICU, and the recent introduction of generic formulations of midazolam has decreased the drug-acquisition cost for many hospitals. Optimal sedation for ICU patients often requires BZ and concomitant therapy with drugs such as haloperidol, dexmedetomidine, opioids, and so forth, to reduce untoward side effects and, perhaps, overall drug costs. Flumazenil, a specific BZ antagonist, can be used for diagnostic or therapeutic reversal of BZ agonists when appropriate. Most experienced intensivists recommend an individualized approach to sedation and titration of anxiolysis to maximize efficacy, minimize side effects, and optimize cost effectiveness in the ICU. New CNS monitors of the EEG, such as the BIS or entropy EEG monitors, may refine titration algorithms further in the near future.


Subject(s)
Anti-Anxiety Agents , Intensive Care Units , Anti-Anxiety Agents/pharmacokinetics , Anti-Anxiety Agents/pharmacology , Anti-Anxiety Agents/therapeutic use , Critical Care , Diazepam/pharmacology , Half-Life , Humans , Lorazepam/pharmacology , Midazolam/pharmacology
6.
J Cardiothorac Vasc Anesth ; 14(5): 571-5, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11052441

ABSTRACT

OBJECTIVE: To evaluate the use of a high dose of nitroglycerin (NTG) for prophylaxis against myocardial ischemia and infarction in patients undergoing coronary artery bypass graft (CABG) surgery with accelerated recovery. DESIGN: Prospective, double-blind, placebo-controlled randomized study. SETTING: A university-based medical center. PARTICIPANTS: Forty adult patients presenting for elective CABG surgery. INTERVENTIONS: Forty patients were divided into 2 blinded study groups. Twenty patients received 2 microg/kg/min of NTG starting before induction of anesthesia and continuing for 6 hours after extubation in the intensive care unit. The placebo group (n = 20) received normal saline during this same interval. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, incidence and severity of myocardial ischemia, and myocardial infarction rates were determined. There were no differences in hemodynamic parameters between groups. The incidence of ischemia was approximately 35% in each group. Myocardial infarction (as determined by elevated creatine kinase-MB fraction, troponin I, and electrocardiogram criteria) was 10% in the placebo group and 5% in the NTG group (p = 0.234). CONCLUSIONS: This study shows a high incidence of myocardial ischemia and infarction in patients presenting for CABG surgery with an accelerated recovery management scheme. NTG was well tolerated clinically; however, it was not found to be protective against myocardial ischemia or infarction in this setting.


Subject(s)
Coronary Artery Bypass/adverse effects , Myocardial Ischemia/prevention & control , Nitroglycerin/therapeutic use , Vasodilator Agents/therapeutic use , Adult , Double-Blind Method , Female , Humans , Male , Middle Aged , Myocardial Infarction/prevention & control , Prospective Studies
7.
Anesthesiology ; 92(2): 338-46, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10691218

ABSTRACT

BACKGROUND: Dopamine is an agonist of alpha, beta, and dopaminergic receptors with varying hemodynamic effects depending on the dose of drug being administered. The purpose of this study was to measure plasma concentrations of dopamine in a homogeneous group of healthy male subjects to develop a pharmacokinetic model for the drug. Our hypothesis was that dopamine concentrations can be predicted from the infusion dose using a population-based pharmacokinetic model. METHODS: Nine healthy male volunteers aged 23 to 45 yr were studied in a clinical research facility within our academic medical center. After placement of venous and arterial catheters, dopamine was infused at 10 microg x kg(-1) x min(-1) for 10 min, followed by a 30-min washout period. Subsequently, dopamine was infused at 3 microg x kg(-1) x min(-1) for 90 min, followed by another 30-min washout period. Timed arterial blood samples were centrifuged, and the plasma was analyzed by high-performance liquid chromatography. Mixed-effects pharmacokinetic models using NONMEM software (NONMEM Project Group, University of California, San Francisco, CA) were used to determine the optimal compartmental pharmacokinetic model for dopamine. RESULTS: Plasma concentrations of dopamine varied from 12,300 to 201,500 ng/l after 10 min of dopamine infusion at 10 microg x kg(-1) x min(-1). Similarly, steady-state dopamine concentrations varied from 1,880 to 18,300 ng/l in these same subjects receiving 3-microg x kg(-1) x min(-1) infusions for 90 min. A two-compartment model adjusted for body weight was the best model based on the Schwartz-Bayesian criterion. CONCLUSIONS: Despite a homogeneous population of healthy male subjects and weight-based dosing, there was 10- to 75-fold intersubject variability in plasma dopamine concentrations, making standard pharmacokinetic modeling of less utility than for other drugs. The data suggest marked intraindividual and interindividual variability in dopamine distribution and/or metabolism. Thus, plasma dopamine concentrations in patients receiving dopamine infusion at identical rates may vary profoundly. Our data suggest that dosing dopamine based on body weight does not yield predictable blood concentrations.


Subject(s)
Dopamine/pharmacokinetics , Adult , Dopamine/administration & dosage , Dopamine/blood , Half-Life , Humans , Infusions, Intravenous , Male , Models, Biological
9.
Anesthesiology ; 93(6): 1398-400, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11149432

ABSTRACT

BACKGROUND: A recently released dopamine-1 receptor agonist, fenoldopam, increases intraocular pressure (IOP) in both healthy volunteers and patients with chronic ocular hypertension. Dopamine, a potent agonist at both dopamine-1 and -2 receptors, is frequently infused in critically ill patients for its inotropic, renal vasodilatory, and natriuretic effects. The authors hypothesized that low doses of dopamine would significantly increase IOP. METHODS: Patients in the intensive care unit who were currently receiving dopamine infusions of less than 5 microg x kg(-1) x min(-1) were studied After local ocular anesthesia was obtained, baseline IOP was measured in each eye with a hand-held tonometer. IOP was then determined after dopamine was discontinued. RESULTS: Twenty-three patients received a mean dopamine infusion of 2.6 +/- 0.2 microg x kg(-1) x min(-1). Twelve of the 23 patients were receiving mechanical ventilation during the study. Mean IOPs in nonventilated patients (n = 11) off dopamine were 13.1 +/- 0.9 mmHg (left eye) and 12.6 +/- 0.9 mmHg (right eye). Mean IOPs for the same patients receiving dopamine were significantly higher at 16.1 +/- 0.9 mmHg (left eye) and 15.9 +/- 1.1 mmHg (right eye). Mean IOPs in intubated patients (n = 12) off dopamine were 12.3 +/- 0.7 mmHg (left eye) and 12.5 +/- 1.2 mmHg (right eye). Mean IOPs for the same patients while receiving dopamine were significantly higher in intubated patients at 17.8 +/- 1.3 mmHg (left eye) and 17.3 +/- 1.3 mmHg (right eye). The average mean elevation in IOP in patients while receiving dopamine was significantly higher in intubated patients as compared with nonintubated patients (5.2 +/- 0.9 mmHg vs. 3.1 +/- 0.6 mmHg). CONCLUSIONS: Commonly used doses of dopamine are associated with increased IOP in critically ill patients. Although normal patients should be able to tolerate this elevation safely for several weeks, there may be a potential risk in patients with preexisting glaucomatous nerve damage or ocular hypertension, especially if they are sedated and mechanically ventilated.


Subject(s)
Critical Illness , Dopamine Agonists/adverse effects , Dopamine/adverse effects , Intraocular Pressure/drug effects , Adult , Aged , Dopamine/administration & dosage , Dopamine Agonists/administration & dosage , Humans , Middle Aged , Respiration, Artificial
10.
J Clin Monit Comput ; 16(3): 201-9, 2000.
Article in English | MEDLINE | ID: mdl-12578104

ABSTRACT

OBJECTIVE: Pulse oximetry (SpO2) is the non-invasive standard for monitoring arterial oxygen saturation in patients undergoing anesthesia, but is subject to external interference by motion artifact, peripheral vasoconstriction, and low cardiac output. We hypothesized that oximetry signals could be acquired from the esophagus when peripheral pulse oximetry is unobtainable. Therefore, we tested an esophageal stethoscope which incorporates transverse oximetry photodetectors and emitters in patients undergoing coronary bypass surgery. METHODS: Immediately after induction of general anesthesia in 10 coronary artery bypass (CABG) patients, Criticare and Nellcor digital probes were positioned on the left hand, concurrent with placement of an esophageal SpO2 probe. A computer recorded 5,910 matched oximetry signals every 15 sec during an average of 2.5 hrs. All SpO2 measurements were before, and immediately after non-pulsatile, hypothermic cardiopulmonary bypass. Data represent the percentage (median value [range]) of the total monitored time that a SpO2 value was displayed. RESULTS: The Nellcor (99.8%, range 6.5-100%) and Criticare (99.7%, range 36.6-100%) acquired and displayed saturation signals more frequently (p = 0.003) than the esophageal monitor (75.3%, range 42.1-95.8%). The two standard digital oximeters had a mean difference of 0.9%, with a standard deviation of the differences of 0.9. The esophageal probe had a mean difference of -5.2% and -4.8%, with standard deviation of differences of 8.0 and 7.7 (compared to the Nellcor and Criticare monitors, respectively). A second-generation prototype shielded from electrocautery interference was tested in an additional 4 patients. The shielded prototype displayed signals more frequently (96.7%, range 68.4-100%) than the original esophageal prototype. CONCLUSIONS: Digital pulse oximetry failure is common in CABG patients, probably because of marginal cardiac output and peripheral vasoconstriction associated with hypothermia. Our study could not confirm that esophageal technology, which utilizes the esophagus as a site of transflectance oximetry, was superior to conventional digital pulse oximetry.


Subject(s)
Coronary Artery Bypass , Esophagus , Monitoring, Physiologic , Oximetry/instrumentation , Adult , Aged , Anesthesia, General , Female , Humans , Male , Middle Aged , Monitoring, Intraoperative , Monitoring, Physiologic/instrumentation , Oximetry/methods , Oxyhemoglobins/analysis , Signal Processing, Computer-Assisted
11.
J Cardiothorac Vasc Anesth ; 13(5): 555-61, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10527224

ABSTRACT

OBJECTIVES: To determine (1) if perioperative use of esmolol in major vascular surgery patients provides strict heart rate (HR) control, (2) what doses of esmolol are required to do this, and (3) does this control influence myocardial ischemia or result in adverse consequences. DESIGN: Prospective study of 40 patients randomized to two groups: The HR was controlled to either less than 80 beats/min (group 80) or less than 110 beats/min (group 110) using esmolol. Patients were monitored continuously for electrocardiographic changes perioperatively. HR control began after induction of anesthesia and continued for 48 hours thereafter. SETTING: Operating room and intensive care unit. PATIENTS: Patients undergoing abdominal vascular surgery involving aortic cross-clamping. INTERVENTIONS: Esmolol was titrated until the target HR was met. MEASUREMENTS AND RESULTS: Only one patient demonstrated an adverse effect. The median infusion rates were 100 and 12.5 microg/kg/min for groups 80 and 110. Target HR was met less in group 80 than in group 110, primarily in the postoperative period. Ischemia patterns were not significantly different between groups. CONCLUSION: Using esmolol for HR control in the intraoperative period for abdominal vascular surgery patients is effective and safe. HR control was much less effective in the postoperative period, but esmolol is safe when used at recommended doses. Further study with a larger number of patients is necessary to determine whether strict HR control with esmolol affects the incidence of myocardial ischemia or infarction in this patient population.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Aorta, Abdominal/surgery , Propanolamines/therapeutic use , Adrenergic beta-Antagonists/adverse effects , Aged , Electrocardiography , Female , Heart Rate/drug effects , Humans , Intraoperative Complications/prevention & control , Intraoperative Period , Male , Middle Aged , Monitoring, Intraoperative , Myocardial Ischemia/prevention & control , Postoperative Complications/prevention & control , Propanolamines/adverse effects , Prospective Studies
12.
Anesthesiology ; 91(2): 345-54, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10443595

ABSTRACT

BACKGROUND: Although the ulnar nerve is the most frequent site of perioperative neuropathy, the mechanism remains undefined. The ulnar nerve appears particularly susceptible to external pressure as it courses through the superficial condylar groove at the elbow, rendering it vulnerable to direct compression and ischemia However, there is disagreement among major anesthesia textbooks regarding optimal positioning of the arm during anesthesia. METHODS: To determine which arm position (supination, neutral orientation, or pronation) minimizes external pressure applied to the ulnar nerve, we studied 50 awake, normal volunteers using a computerized pressure sensing mat. An additional group of 15 subjects was tested on an operating table with their arm in 30 degrees, 60 degrees, and 90 degrees of abduction, as well as in supination, neutral orientation, and pronation. To determine the onset of clinical paresthesia compared to the onset and severity of somatosensory evoked potential (SSEP) electrophysiologic changes, we studied a separate group of 16 male volunteers while applying intentional pressure directly to the ulnar nerve. Data are presented as mean (median; range). RESULTS: Supination minimizes direct pressure over the ulnar nerve at the elbow (2 mmHg [0; 0-23]; n = 50), compared with both neutral forearm orientation (69 mmHg [22; 0-220]; P < 0.0001), as well as pronation (95 mmHg [61; 0-220]; P < 0.0001). Neutral forearm orientation also results in significantly less pressure over the ulnar nerve compared to pronation (P < or = 0.04). The estimated contact area of the ulnar nerve with the weight-bearing surface was significantly (P < 0.0001) smaller in the supine position (2.2 cm2 [0.5; 0-9]; n = 50) compared with both neutral orientation (5.5 cm2 [5.0; 0-13]) and pronation (5.8 cm2 [6; 0-12]). With the forearm in neutral orientation, ulnar nerve pressure decreased significantly (P < or = 0.01; n = 15) as the arm was abducted at the shoulder from 0 degrees to 90 degrees. In the 16 male subjects tested, notable alterations in ulnar nerve SSEP signals (decrease > or = 20% in N9-N9' amplitude) were detected in 15 of 16 awake males during application of intentional pressure to the ulnar nerve. However, eight of these subjects did not perceive a paresthesia, even as SSEP waveform amplitudes were decreasing 23-72%. Two of these eight subjects manifested severe decreases in SSEP amplitude (> or = 60%). CONCLUSIONS: Extrapolating these results to the clinical setting, the supinated arm position is likely to minimize pressure over the ulnar nerve. With the forearm in neutral orientation, pressure over the ulnar nerve decreases as the arm is abducted between 30 degrees and 90 degrees. In addition, up to one half of male patients may fail to perceive or experience clinical symptoms of ulnar nerve compression sufficient to elicit SSEP changes.


Subject(s)
Anesthesia/adverse effects , Evoked Potentials, Somatosensory , Peripheral Nervous System Diseases/etiology , Posture , Ulnar Nerve , Adult , Aged , Arm , Humans , Male , Middle Aged , Pressure
14.
Anesthesiology ; 90(6): 1624-35, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10360861

ABSTRACT

BACKGROUND: Epsilon-aminocaproic acid (EACA) is commonly infused during cardiac surgery using empiric dosing schemes. The authors developed a pharmacokinetic model for EACA elimination in surgical patients, tested whether adjustments for cardiopulmonary bypass (CPB) would improve the model, and then used the model to develop an EACA dosing schedule that would yield nearly constant EACA blood concentrations. METHODS: Consenting patients undergoing elective coronary artery surgery received one of two loading doses of EACA, 30 mg/kg (group I, n = 7) or 100 mg/kg (group II, n = 6) after CPB, or (group III) a 100 mg/kg loading dose before CPB and a 10 mg x kg(-1) x h(-1) maintenance infusion continued for 4 h during and after CPB (n = 7). Two patients with renal failure received EACA in the manner of group III. Blood concentrations of EACA, measured by high-performance liquid chromatography, were subjected to mixed-effects pharmacokinetic modeling. RESULTS: The EACA concentration data were best fit by a model with two compartments and corrections for CPB. The elimination rate constant k10 fell from 0.011 before CPB to 0.0006 during CPB, returning to 0.011 after CPB. V1 increased 3.8 l with CPB and remained at that value thereafter. Cl1 varied from 0.08 l/min before CPB to 0.007 l/min during CPB and 0.13 l/min after CPB. Cl2 increased from 0.09 l/min before CPB to 0.14 l/min during and after CPB. Two patients with renal failure demonstrated markedly reduced clearance. Using their model, the authors predict that an EACA loading infusion of 50 mg/kg given over 20 min and a maintenance infusion of 25 mg x kg(-1) x h(-1) would maintain a nearly constant target concentration of 260 microg/ml. CONCLUSIONS: EACA clearance declines and volume of distribution increases during CPB. The authors' model predicts that more stable perioperative EACA concentrations would be obtained with a smaller loading dose (50 mg/kg given over 20 min) and a more rapid maintenance infusion (25 mg x kg(-1) x h(-1)) than are typically employed.


Subject(s)
Aminocaproic Acid/pharmacokinetics , Antifibrinolytic Agents/pharmacokinetics , Coronary Artery Bypass , Adolescent , Aged , Female , Humans , Male , Metabolic Clearance Rate , Middle Aged
15.
Anesthesiology ; 89(1): 49-57, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9667293

ABSTRACT

BACKGROUND: Patients may receive more than one positive inotropic drug to improve myocardial function and cardiac output, with the assumption that the effects of two drugs are additive. The authors hypothesized that combinations of dobutamine and epinephrine would produce additive biochemical and hemodynamic effects. METHODS: The study was performed in two parts. Phase 1 used human lymphocytes in an in vitro model of cyclic adenosine monophosphate (cAMP) generation in response to dobutamine (10(-8) to 10(-4) M) or epinephrine (10(-9) M to 10(-5) M), and dobutamine and epinephrine together. Phase 2 was a clinical study in patients after aortocoronary artery bypass in which isobolographic analysis compared the cardiotonic effects of dobutamine (1.25, 2.5, or 5 microg x kg(-1) x min(-1)) or epinephrine (10, 20, or 40 ng x kg(-l) x min(-1)), alone or in combination. RESULTS: In phase 1, dobutamine increased cAMP production 41%, whereas epinephrine increased cAMP concentration approximately 200%. However, when epinephrine (10(-6) M) and dobutamine were combined, dobutamine reduced cAMP production at concentrations between 10(-6) to 10(-4) M (P = 0.001). In patients, 1.25 to 5 microg x kg(-1) x min(-1) dobutamine increased the cardiac index (CI) 15-28%. Epinephrine also increased the CI with each increase in dose. However, combining epinephrine with the two larger doses of dobutamine (2.5 and 5microg x kg(-1) x mi(-1)) did not increase the CI beyond that achieved with epinephrine and the lowest dose of dobutamine (1.25 microg x kg(-1) x min(-1)). In addition, the isobolographic analysis for equieffective concentrations of dobutamine and epinephrine suggests subadditive effects. CONCLUSIONS: Dobutamine inhibits epinephrine-induced production of cAMP in human lymphocytes and appears to be subadditive by clinical and isobolographic analyses of the cardiotonic effects. These findings suggest that combinations of dobutamine and epinephrine may be less than additive.


Subject(s)
Adrenergic Agonists/administration & dosage , Cardiotonic Agents/administration & dosage , Coronary Artery Bypass , Cyclic AMP/biosynthesis , Dobutamine/administration & dosage , Epinephrine/administration & dosage , Lymphocytes/drug effects , Postoperative Complications/prevention & control , Cells, Cultured , Dose-Response Relationship, Drug , Heart Rate/drug effects , Hemodynamics/drug effects , Humans , Lymphocytes/metabolism
16.
Anesthesiology ; 88(6): 1437-46, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9637635

ABSTRACT

BACKGROUND: The authors hypothesized that shorter-acting opioid and neuromuscular blocking drugs would be associated with reductions in duration of intubation, length of stay (LOS) in the intensive care unit (ICU) after tracheal extubation, or postoperative (exclusive of ICU) LOS, and that shorter durations of intubation would be associated with reduced ICU LOS after extubation and postoperative (exclusive of ICU) LOS. METHODS: One-thousand ninety-four patients undergoing primary coronary artery bypass graft surgery at 40 academic health centers were studied. Multiple patient-related factors were included in multivariate models for hypothesis testing. RESULTS: The duration of tracheal intubation, ICU LOS after extubation, and postoperative (exclusive of ICU) LOS all varied significantly by site. There was no difference between vecuronium and pancuronium in duration of intubation, ICU LOS after extubation, or postoperative (exclusive of ICU) LOS. Use of sufentanil rather than fentanyl was associated with a significant (P=0.045) reduction of 1.9 h (95% CI, 0.04 to 4.1 h) in duration of tracheal intubation but had no significant effect on ICU LOS after extubation, total ICU LOS, postoperative (exclusive of ICU) LOS, or total postoperative LOS. The authors' best model predicts a complex association between increasing duration of intubation and both ICU LOS after tracheal extubation and postoperative (exclusive of ICU) LOS, which was associated with an increase in those measures when duration of intubation exceeded 7.3 or 3 h, respectively. CONCLUSIONS: The LOS measures varied considerably among the institutions. Use of shorter-acting opioid and neuromuscular blocking drugs had no association with ICU LOS after tracheal extubation or with postoperative (exclusive of ICU) LOS. Only when the duration of intubation exceeded threshold values was it associated with increased LOS measures.


Subject(s)
Analgesics, Opioid , Coronary Artery Bypass/economics , Intensive Care Units , Neuromuscular Blocking Agents , Aged , Coronary Artery Bypass/methods , Cost Control , Female , Humans , Intubation, Intratracheal , Length of Stay , Male , Middle Aged , Multivariate Analysis , Postoperative Care , Time Factors
17.
Anesth Analg ; 86(4): 683-90, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9539583

ABSTRACT

UNLABELLED: Amrinone and milrinone are phosphodiesterase inhibitors with positive inotropic effects useful for the treatment of ventricular dysfunction after cardiac surgery. Forty-four patients undergoing elective cardiac surgery at four centers received either amrinone (n = 22) or milrinone (n = 22) in a randomized, blind fashion. Immediately after separation from cardiopulmonary bypass (CPB), two bolus doses of either amrinone 0.75 mg/kg or milrinone 25 microg/kg were administered over 30 s, separated by 5 min. Hemodynamic measurements were recorded before each dose and at the end of the 10-min study. Both amrinone and milrinone increased the cardiac index (48% vs 52%, P = not significant [NS] for amrinone and milrinone, respectively). There was a small increase in mean arterial pressure (MAP) after amrinone administration (from 68 +/- 3 to 72 +/- 3 mm Hg at 10 min, P < 0.05) with no significant change in MAP after milrinone administration. Central venous pressure was significantly higher in the amrinone group at baseline and 5 min (12 vs 10 mm Hg and 11 vs 10 mm Hg, respectively; P < 0.05). Systemic and pulmonary vascular resistances decreased significantly and to a similar extent after either amrinone or milrinone administration. Phenylephrine was required in 11 of 22 patients receiving amrinone and in 11 of 22 patients receiving milrinone to maintain arterial blood pressure. The proportion of patients requiring an intravascular volume infusion (15 of 22 vs 17 of 22, P = NS) and the total fluid volume infused were similar (402 +/- 57 vs 350 +/- 49 mL, P = NS for amrinone and milrinone, respectively). Amrinone and milrinone seem to have similar hemodynamic effects after CPB, with the exception of blood pressure, although the need for vasopressor support of blood pressure did not differ. Selection between these two drugs may include nonhemodynamic considerations such as cost. IMPLICATIONS: Amrinone and milrinone are drugs that improve cardiac contraction. Their effects have never been directly compared in patients. We found that amrinone and milrinone produced similar hemodynamic effects in adult patients undergoing cardiac surgery. Choice between the two drugs can be based on nonhemodynamic considerations such as cost.


Subject(s)
Amrinone/therapeutic use , Cardiac Surgical Procedures , Cardiotonic Agents/therapeutic use , Phosphodiesterase Inhibitors/therapeutic use , Pyridones/therapeutic use , Adult , Aged , Amrinone/administration & dosage , Blood Pressure/drug effects , Cardiac Output/drug effects , Cardiopulmonary Bypass , Cardiotonic Agents/administration & dosage , Central Venous Pressure/drug effects , Drug Costs , Elective Surgical Procedures , Female , Fluid Therapy , Hemodynamics/drug effects , Humans , Injections, Intravenous , Lung/blood supply , Male , Middle Aged , Milrinone , Myocardial Contraction/drug effects , Phenylephrine/therapeutic use , Phosphodiesterase Inhibitors/administration & dosage , Plasma Substitutes/therapeutic use , Pyridones/administration & dosage , Single-Blind Method , Vascular Resistance/drug effects , Vasoconstrictor Agents/therapeutic use , Ventricular Dysfunction/prevention & control
19.
Can J Anaesth ; 44(11): 1220, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9398969
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