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Biomedical subjects

R C Prielipp

Publications and source records attributed to R C Prielipp.

At least 19 recordsLinked to original sources
PubMed2000

Prophylactic nitroglycerin did not reduce myocardial ischemia during accelerated recovery management of coronary artery bypass graft surgery patients.

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.

Adult↗
PubMed2000

Pharmacokinetics of dopamine in healthy male subjects.

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.

Adult↗
PubMed2000

Dopamine and intraocular pressure in critically ill patients.

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.

Adult↗
PubMed1999

The safety and effectiveness of esmolol in the perioperative period in patients undergoing abdominal aortic surgery.

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.

Adrenergic beta-Antagonists↗
PubMed1999

Pharmacokinetics of epsilon-aminocaproic acid in patients undergoing aortocoronary bypass surgery.

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.

Adolescent↗
PubMed1999

Ulnar nerve pressure: influence of arm position and relationship to somatosensory evoked potentials.

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.

Adult↗
PubMed1998

A multicenter, randomized, blind comparison of amrinone with milrinone after elective cardiac surgery.

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.

Adult↗
PubMed1998

Do shorter-acting neuromuscular blocking drugs or opioids associate with reduced intensive care unit or hospital lengths of stay after coronary artery bypass grafting? CABG Clinical Benchmarking Data Base Participants.

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.

Aged↗
PubMed1998

Dobutamine antagonizes epinephrine's biochemical and cardiotonic effects: results of an in vitro model using human lymphocytes and a clinical study in patients recovering from cardiac surgery.

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.

Adrenergic Agonists↗
PubMed1997

Stethoscopy.

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Anesthesia↗
PubMed1997

Topical ice slurry prevents brain rewarming during deep hypothermic circulatory arrest in newborn sheep.

OBJECTIVES: To measure the effect of ice slurry topical cooling on brain surface temperature during deep hypothermic circulatory arrest. DESIGN: This was a prospective, controlled experiment. SETTING: Animal laboratory at a university hospital. PARTICIPANTS: Five control lambs, five treatment (ice slurry) lambs. INTERVENTIONS: Animals were studied in two groups: the study group had topical cooling of the head with ice slurry started immediately before circulatory arrest and continued throughout the period of circulatory arrest; control group lambs received no supplemental topical cooling. MEASUREMENTS AND MAIN RESULTS: Brain surface temperature, scalp, nasopharyngeal, and rectal temperatures were measured at 5-minute intervals during 45 minutes of circulatory arrest. Lambs receiving topical cooling of the head with ice slurry had a statistically significant decrease in brain surface temperature of 2.2 +/- 1.2 degrees C during circulatory arrest, whereas brain surface temperature increased 1.2 +/- 0.3 degrees C, in control lambs. Equilibration of temperature between the scalp and brain in control lambs produced rewarming of the brain surface. CONCLUSIONS: Topical cooling of the head with ice slurry in newborn lambs lowers brain surface temperature during deep hypothermic circulatory arrest. Surrogate temperature monitoring locations such as nasopharyngeal and rectal temperatures varied significantly and do not accurately reflect changes in brain surface temperature.

Animals↗
PubMed1997

Dose response, recovery, and cost of doxacurium as a continuous infusion in neurosurgical intensive care unit patients.

OBJECTIVES: To determine the optimal dosing of doxacurium as a continuous infusion in neurosurgical patients with traumatic brain injury; to determine the effects of bolus administration of doxacurium on heart rate (HR), blood pressure (BP), and intracranial pressure (ICP); to monitor neuromuscular recovery after discontinuation of prolonged doxacurium infusion; and to compare the cost of doxacurium with other current neuromuscular blocking drugs. DESIGN: Prospective, open-label study. SETTING: Neurosurgical intensive care unit (ICU) of a university-affiliated teaching hospital. PATIENTS: Eight critically ill, mechanically ventilated patients with traumatic head injury and normal renal and hepatic function. Patients had ICP monitoring. INTERVENTIONS: A bolus injection of doxacurium (0.05 mg/kg) followed by a continuous infusion (0.015 mg/kg/hr), adjusted to maintain one twitch during Train-of-Four nerve stimulation of the adductor pollicis muscle. MEASUREMENTS AND MAIN RESULTS: Bolus injections of doxacurium did not alter the HR, BP, or ICP. Patients were paralyzed 66 +/- 12 (SEM) hrs, with recovery of the fourth twitch occurring 118 +/- 19 mins after infusion of the doxacurium was discontined. There were no incidences of prolonged weakness, myopathy, or other adverse events. CONCLUSIONS: Continuous infusion of doxacurium provides stable neuromuscular blockade for neurosurgical patients with traumatic brain injury. Doxacurium is devoid of clinically important interactions with HR, BP, or ICP and is less costly than other neuromuscular blockers used in the ICU.

Adult↗
PubMed1997

Renal dose dopamine does not alter the response to beta-adrenergic stimulation by isoproterenol in healthy human volunteers.

OBJECTIVES: To determine if renal dose dopamine (3 microg/kg/min) alters the heart rate (HR) by itself, or if a dopamine infusion alters the HR response to bolus doses of the beta-adrenergic agonist isoproterenol in healthy human subjects. DESIGN: Prospective study. SETTING: Clinical laboratory of a university-affiliated academic medical center. SUBJECTS: A total of 15 healthy nonpregnant women and men aged 21 to 44 years. INTERVENTIONS: Subjects were monitored continuously with bedside ECG, pulse oximetry, and ambulatory ECG recording to measure the maximal HR response to separate injections of 10, 20, and 30 ng/kg of isoproterenol, given before, during, and after the infusion of 3 microg/kg/min of dopamine. MEASUREMENTS AND MAIN RESULTS: Dopamine in the absence of isoproterenol did not alter baseline HR significantly (62.7+/-2.2 beats/min without dopamine; 65.4+/-2.2 with dopamine; p=0.15). All three doses of isoproterenol increased HR significantly above baseline, both in the presence and absence of dopamine (p<0.001). Dopamine infusion resulted in a higher HR following isoproterenol only for the 20-ng/kg dose. The incremental increases in HR, defined as the difference between peak HR following isoproterenol and baseline HR, were not increased during dopamine infusion for any of the doses of isoproterenol. Nausea was reported by 5 of the 15 subjects during the dopamine infusion. CONCLUSIONS: In healthy human subjects, infusion of 3 microg/kg/min of dopamine does not significantly increase the HR when combined with beta-adrenergic stimulation using isoproterenol, suggesting neither an additive nor antagonistic interaction between the two drugs. While our study did not demonstrate an increase in HR in healthy subjects, the risk of increasing the chronotropic response to beta-adrenergic inotropic medications with "renal dose" dopamine in critically ill patients needs to be investigated. The frequency of nausea during dopamine infusion also may influence consideration of using dopamine to augment splanchnic blood flow and renal function in conscious patients.

Adrenergic beta-Agonists↗