Anesth Analg 1999;89:1116
© 1999 International Anesthesia Research Society
CARDIOVASCULAR ANESTHESIA
Nicardipine Intravenous Bolus Dosing for Acutely Decreasing Arterial Blood Pressure During General Anesthesia for Cardiac Operations: Pharmacokinetics, Pharmacodynamics, and Associated Effects on Left Ventricular Function
Albert T. Cheung, MD,
Dmitri V. Guvakov, MD,
Stuart J. Weiss, MD, PhD,
Joseph S. Savino, MD,
Ivan S. Salgo, MD, and
Qing C. Meng, PhD
Department of Anesthesia, University of Pennsylvania, Philadelphia, Pennsylvania
Address correspondence and reprint requests to Albert T. Cheung, MD, Department of Anesthesia, Dulles 7, University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104-4283. Address e-mail to cheungal{at}mail.med.upenn.edu
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Abstract
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The objective of this study was to evaluate the efficacy of nicardipine, a dihydropyridine calcium channel antagonist, administered as an IV bolus dose to acutely decrease arterial pressure in anesthetized cardiac surgical patients. We performed a double-blind, randomized, self-controlled, dose-ranging study in 40 adult cardiac surgical patients to determine the pharmacokinetics and pharmacodynamics of nicardipine 0.25 mg, 0.50 mg, 1.00 mg, and 2.00 mg administered as an IV bolus. Transesophageal echocardiography was used to assess left ventricular preload, afterload, and global systolic function. Plasma nicardipine concentration was measured using high-performance liquid chromatography. Nicardipine selectively decreased arterial pressure in a dose-dependent manner with a maximum response within 100 s and recovery to half the maximum response within 3–7 min without associated changes in heart rate. The decreases in arterial pressure were associated with only small decreases in left ventricular end-systolic wall stress and small increases in global left ventricular systolic function without changes in left ventricular end-diastolic cavity area or cardiac output. The time course for nicardipine bolus was consistent with a two-compartment pharmacokinetic model with rapid redistribution from a small central compartment.
Implications: Nicardipine was effective for selectively decreasing arterial blood pressure acutely, but had no effects on ventricular preload or cardiac output. The absence of dose-dependent changes in cardiac output, left ventricular systolic performance, and left ventricular afterload despite significant decreases in arterial pressure suggested that nicardipine had a small negative inotropic action.
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Introduction
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Drugs for acute blood pressure control are often required during cardiac operations. Reports indicate that 30%–56% of cardiac surgical patients require antihypertensive therapy in the perioperative period (1–4). Clinical studies have suggested that nicardipine, a dihydropyridine calcium channel antagonist administered by continuous IV infusion, decreases blood pressure by selective arterial vasodilation, has less negative inotropic action than nifedipine, and exerts no direct electrophysiologic effects (5–8). These properties of nicardipine suggest that it would be useful in situations requiring an acute decrease in arterial pressure during anesthesia in patients with cardiac disease.
IV bolus administration of nicardipine has been used to attenuate the circulatory responses to tracheal intubation and for the treatment of paroxysmal hypertension after coronary artery surgery (9,10). The short-term hemodynamic effects of nicardipine administered by IV bolus injection to awake hypertensive patients suggest that its onset and duration of action would be suitable for acutely decreasing arterial pressure in cardiac surgical patients (11). However, dose responses and circulatory actions of nicardipine in anesthetized patients may differ from those of awake patients. Furthermore, the pharmacokinetics and pharmacodynamic actions of nicardipine administered as an IV bolus dose to anesthetized patients with cardiac disease have not been fully characterized. Previous studies suggest that the net hemodynamic effects of nicardipine are the consequence of its direct actions on the cardiovascular system together with indirect effects produced by reflex sympathetic nervous system activation in response to the decrease in arterial pressure (12).
This study was designed to test the hypothesis that nicardipine administered as an IV bolus dose to anesthetized cardiac surgical patients acutely and predictably decreases arterial pressure without reflex tachycardia because sympathetic nervous system reflexes would be attenuated by general anesthesia. The secondary objective was to characterize the pharmacokinetic and pharmacodynamic properties of nicardipine administered as an IV bolus over a range of doses. Intraoperative transesophageal echocardiography (TEE) was used to investigate the acute effects of nicardipine bolus on left ventricular preload, afterload, and systolic performance.
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Methods
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Elective cardiac surgical patients who provided written informed consent were enrolled in an investigational protocol approved by our institutional review board. The study was a prospective, randomized, double-blind, self-controlled, four-arm dose-ranging study of nicardipine administered by IV bolus injection. Patients undergoing an emergency operation, with preoperative serum creatinine concentration >2.0 mg/dL, receiving dihydropyridine calcium channel blockers or in whom TEE could not be performed safely because of esophageal or cervical spine diseases were excluded from the study.
Patients were randomized into 1 of 4 nicardipine dose groups: Group 1, nicardipine 0.25 mg; Group 2, nicardipine 0.50 mg; Group 3, nicardipine 1.00 mg; and Group 4, nicardipine 2.00 mg until data were obtained for 10 patients in each dose group. Nicardipine was administered as an IV bolus by rapid injection (over <5 s) directly into the right atrial port of the pulmonary artery catheter. Nicardipine was administered only after wire closure of the median sternotomy near the end of the operation if the systolic arterial pressure exceeded 120 mm Hg. General anesthesia consisted of midazolam (0.05–0.15 mg/kg), fentanyl (15–75 µg/kg), pancuronium (0.15–0.35 mg/kg), and isoflurane (0.4–1.0 vol%) in oxygen. The rate of IV fluid infusion was adjusted immediately prior to drug administration to maintain a constant right atrial pressure (central venous pressure [CVP]) and then kept constant. Data were used in the analysis only if the inspired concentration of isoflurane was kept constant and no additional IV anesthetic drugs were administered within 15 min prior and 30 min after the administration of nicardipine. Mixed-venous blood samples for measurement of plasma nicardipine concentrations were obtained prior to and at 2, 5, 7, 10, 20, 30, 45, 60, 90, 120, 180, and 240 min after nicardipine injection.
Lead II of the electrocardiogram, the radial arterial pressure (Jelco 20 g 1-3/4 in catheter, Johnson and Johnson Medical, Arlington, TX), pulmonary arterial pressure (Baxter Swan-Ganz CCOmbo, Baxter Healthcare, Irvine, CA), and CVP were recorded continuously on a four-channel chart recorder. All pressure transducers (Sorenson 47616-10, Abbott Laboratories, Chicago, IL) were zeroed at the level of the midaxillary line with the patient in the supine position. Continuous thermodilution cardiac output (CO) and oximetric mixed-venous oxygen saturation (SvO) were recorded before and at 2, 5, 7, 10, 20, and 30 min after nicardipine injection (Vigilance, Baxter Healthcare, Irvine, CA). Baseline hemodynamic variables were the values averaged over 45 s prior to nicardipine injection. Arterial pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP]), pulmonary artery pressure (pulmonary artery systolic [PAS], pulmonary artery diastolic [PAD]), CVP and heart rate (HR) were measured and recorded from the average of three cardiac beats every 15 s for the first 240 s after nicardipine administration, then every 60 s thereafter. The maximum arterial pressure response was defined as the greatest decrease in SBP, DBP, or MAP from baseline after nicardipine administration. The effective duration of nicardipine on arterial blood pressure was estimated by the time for recovery of SBP, DBP, or MAP to half of the maximal response. The time for recovery to half the maximum response was defined as the elapsed time between drug administration and the time at which the change in SBP, DBP, or MAP recovered to 0.5 of the maximum response.
For safety, the SBP of patients was not permitted to exceed 140 mm Hg or decrease to less than 85 mm Hg. For that reason, hypotension after nicardipine administration was defined as a SBP < 85 mm Hg and was treated immediately with IV phenylephrine in 100 µg increments administered into the right atrial port of the pulmonary artery catheter until a SBP 
85 mm Hg was achieved. Similarly, hypertension was defined as a SBP > 140 mm Hg and treated by nitroglycerin or nitroprusside by continuous IV infusion to maintain the SBP in the range of 120–140 mm Hg.
TEE was performed using a 5.0–6.2 MHz TEE ultrasound transducer (Omniplane 2, Hewlett Packard, Hewlett Packard Sonos 2500, Andover MA). The left ventricle (LV) was imaged continuously from the transgastric window in short-axis at the midpapillary muscle level beginning 45 s before and for at least 30 min after nicardipine injection. Cardiac cycles were acquired as digital cine loops and stored on magneto-optical disc at baseline, 0–45 s before nicardipine injection (time point 1), and 45–150 s after nicardipine injection (time point 2), 200–350 s after nicardipine injection (time point 3), and 400–600 s (time point 4) after nicardipine injection. Offline analysis was performed by echocardiographers (ATC and SJW) blinded to the hemodynamic data and nicardipine dose. Manual planimetry of the endocardial and epicardial borders from the digitized images was by the leading edge-to-leading edge technique. The cross-sectional area of papillary muscle bodies within the LV cavity was considered to be part of the blood pool. The LV end-diastolic cross-sectional cavity area (EDA) was used as a TEE index of left ventricular preload (13). The fractional area change (FAC) and LV end-systolic cross-sectional cavity area (ESA) were used as TEE indexes of global systolic performance (14). The LV end-systolic meridional wall stress (ESWS) was used as a TEE index of LV afterload (14).
Plasma nicardipine concentration was measured using high-performance liquid chromatography (HPLC) (15). Plasma samples were extracted by solid-phase extraction using a C18 cartridge. Nicardipine in the purified samples was quantified by HPLC on a reversed-phase C18 column using a mobile phase consisting of 60% (v/v) acetonitrile in 0.02 M NaH2PO4 with a pH of 6.3 and a variable wavelength UV detector set at 254 nm. The HPLC assay had an intraassay coefficient of variation of 2.9%, an interassay coefficient of variation of 5.0%, a limit of detection of 1.6 ng/mL, and a limit of quantification of 5.4 ng/mL (15). Pharmacokinetic analysis was fitted to a two-compartment model with first-order elimination kinetics, C(t) = Ae-
t + Be-ßt, where C(t) was the nicardipine concentration at time t.
Hemodynamic and echocardiographic data were treated as continuous variables. One-way analysis of variance (ANOVA) for repeated measures using the nicardipine dose as the grouping factor was used to test whether the measured variables changed with respect to time after nicardipine injection and were affected by drug dose. ANOVA was used to test if the maximum responses and times to recovery to half the maximum responses were different among groups. A P value <0.05 was considered significant. The Bonferonni correction was used to adjust the probability values when multiple comparisons were performed. Linear regression analysis was used to determine the relationship between plasma nicardipine concentration and the magnitude of decrease in MAP. Curve fitting for the pharmacokinetic model was performed using an iterative nonlinear regression analysis that used a Quasi-Newton least-squares algorithm. Patients who required external cardiac pacing during the period of study (3 in Group 3 and 1 in Group 4) were not included when analyzing changes in HR. Patients who required treatment for hypotension were stratified to assess whether hypotension or its treatment with phenylephrine was associated with specific cardiovascular changes.
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Results
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Of the 47 patients enrolled into the study, 40 met hemodynamic criteria for nicardipine administration and were randomized to the four nicardipine dose groups with 10 patients per group. There were no statistically significant differences in the demographic characteristics of the nicardipine dose groups (Table 1). Thirty-two patients had coronary artery bypass grafting, 3 had reoperation for coronary artery bypass grafting, 4 had aortic valve replacement, and 1 had mitral valve repair.
Nicardipine decreased SBP, DBP, and MAP in a dose-dependent manner (P < 0.001) (Fig. 1). The maximum decrease in SBP (mean ± SD) was 18 ± 2 mm Hg, 32 ± 5 mm Hg, 36 ± 4 mm Hg, and 51 ± 4 mm Hg, after nicardipine 0.25 mg, 0.5 mg, 1.0 mg, and 2.0 mg, respectively, demonstrating a significant dose effect (P < 0.001). The maximum decrease in MAP (mean ± SD) was 15 ± 5 mm Hg, 21 ± 3 mm Hg, 24 ± 4 mm Hg, and 30 ± 2 mm Hg, after nicardipine 0.25 mg, 0.5 mg, 1.0 mg, and 2.0 mg, respectively, also demonstrating a significant dose effect (P < 0.01). The time to maximum decrease in MAP (mean ± SD) was 66 ± 10 s, 63 ± 7 s, 56 ± 10 s, and 101 ± 11 s after nicardipine 0.25 mg, 0.5 mg, 1.0 mg, and 2.0 mg, respectively, and also had a significant dose effect (P < 0.01). CVP did not change in the first 5 min after nicardipine administration (P = 0.22), decreased linearly by an average of 0.9 ± 2.3 mm Hg over 10 min after drug administration (P < 0.001) but that change was independent of drug dose (P = 0.77). PAS and PAD did not change in the first 5 min after nicardipine administration (P > 0.40), but decreased linearly by an average of 2.1 ± 4.6 mm Hg and 1.0 ± 3.4 mm Hg, respectively, over 10 min after drug administration (P < 0.03). The decrease in PAS and PAD was independent of drug dose (P > 0.96). SvO did not change significantly after nicardipine administration (Fig. 2). CO increased significantly by 0.3 ± 0.2 L/min (P < 0.02) in Group 3 only at 600 s after nicardipine 1.0 mg (Fig. 2). HR did not change significantly after nicardipine administration (P = 0.18), and the effect of dose on HR was insignificant (P = 0.87).
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Figure 1. Change in systolic blood pressure, diastolic blood pressure, and mean arterial pressure as a function of time after nicardipine administration (time = 0 s) for Group 1 (nicardipine 0.25 mg, n = 10), Group 2 (nicardipine 0.50 mg, n = 10), Group 3 (nicardipine 1.00 mg, n = 10), Group 4 (nicardipine 2.00 mg, n = 10), and patients who developed hypotension (Hypotensive Group, n = 11). All values are the means for the respective group. Error bars are the SEM and were displayed for Groups 1 and 4 only. Systolic blood pressure (A), diastolic blood pressure (A), and mean arterial pressure (B) changed significantly in response to time after nicardipine administration (P < 0.001) with a significant effect of group (P < 0.001).
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Figure 2. Mean change in cardiac output (CO) and mixed-venous oxygen saturation (SvO) as a function of time after nicardipine administration (time = 0 s) for Group 1 (nicardipine 0.25 mg, n = 10), Group 2 (nicardipine 0.50 mg, n = 10), Group 3 (nicardipine 1.00 mg, n = 10), and Group 4 (nicardipine 2.00 mg, n = 10). All values are the means for the respective group. Error bars are the SEM and were displayed for selected points only. Baseline SvO and CO were acquired 45 s before nicardipine administration. CO increased significantly (P < 0.02) by an average of 0.3 ± 0.2 L/min only in Group 3 (nicardipine 1.00 mg) at 600 s after nicardipine administration. SvO did not change significantly.
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Nicardipine concentrations after IV bolus fitted a two-compartment model using first-order elimination with r2 = 0.99 for all dose groups (Fig. 3, Table 2). The linear regression between the mean change in MAP and the mean plasma nicardipine concentration at each sampling time over the period of 0–30 min after nicardipine administration was significant (P < 0.001) (Fig. 3). Recovery of MAP to half of its maximum response was 3.0 ± 0.8 min, 3.5 ± 0.4 min, 3.5 ± 0.6 min, and 6.9 ± 1.0 min after nicardipine 0.25 mg, 0.5 mg, 1.0 mg, and 2.0 mg, respectively (Table 2), with a significant dose effect (P < 0.005). This time course for the recovery of arterial pressure after the initial decrease was consistent with redistribution half-times of 2.0 min, 2.5 min, 3.5 min, and 5.4 min for nicardipine 0.25 mg, 0.5 mg, 1.0 mg, and 2.0 mg, respectively (Table 2).
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Figure 3. Mean plasma nicardipine concentrations measured by high-performance liquid chromatography for Group 1 (nicardipine 0.25 mg, n = 10), Group 2 (nicardipine 0.50 mg, n = 10), Group 3 (nicardipine 1.00 mg, n = 10), and Group 4 (nicardipine 2.00 mg, n = 10) as a function of time after nicardipine bolus administration (time = 0 s). All values are the means for the respective group. Error bars are the SEM and were displayed for Groups 1 and 4 only. The time course for changes in plasma nicardipine concentrations for each dose group were fitted to a two-compartment pharmacokinetic model with first-order elimination kinetics (r2 = 0.99 for each dose group). Inset: The relationship between the mean (±SEM) change in mean arterial pressure (MAP) with the mean plasma nicardipine concentrations was linear (y = 4.79 - 0.23x, r = 0.88, P < 0.001). Data were combined from all nicardipine dose groups over the time period of 0–600 s after drug administration.
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The acute effects of nicardipine on TEE indices of LV function were small in comparison with the effects on arterial pressure. ESWS decreased at time point 2 in all groups, but the decrease was statistically significant only in the 2.0 mg dose group (P < 0.001). At time point 2, ESA decreased and FAC increased in all groups, but the changes were not significant. EDA did not change significantly except at time point 4 (P < 0.001) in the 2.0 mg group (Fig. 4).
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Figure 4. Mean left ventricle end-systolic meridional wall stress (ESWS), left ventricle end-diastolic area (EDA), left ventricle end-systolic area (ESA), and fractional area change (FAC) for Group 1 (nicardipine 0.25 mg, n = 10), Group 2 (nicardipine 0.50 mg, n = 10), Group 3 (nicardipine 1.00 mg, n = 10), Group 4 (nicardipine 2.00 mg, n = 10), and patients who developed hypotension (Hypotensive Group, n = 11) after nicardipine administration. The echocardiographic parameters were measured at 0–45 s before nicardipine administration (Time point 1), 45–150 s after nicardipine (Time point 2), 200–350 s after nicardipine (Time point 3), and 400–600 s after nicardipine (Time point 4). All values were the mean for the group. Error bars are the SEM and shown only for selected points. P values were for comparisons (paired Students t-test with Bonferonni correction) between the measured parameter at the specified time and the value of the parameter prior to drug administration (Time point 1).
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Hypotension (SBP < 85 mm Hg) after nicardipine administration occurred in 11 patients and was more frequent in the higher dose groups. Hypotension occurred in 0/10, 2/10, 3/10, and 6/10 patients after nicardipine 0.25 mg, 0.5 mg, 1.0 mg, and 2.0 mg, respectively. Despite treatment with phenylephrine, patients who developed hypotension after nicardipine had a small, but significant decrease in ESWS (P < 0.001), increase in FAC (P < 0.05), decrease in ESA (P < 0.005), and decrease in EDA (P < 0.05) at time point 2.
Treatment for SBP > 140 mm Hg with IV nitroglycerin or nitroprusside was required in 4/10, 2/10, 0/10, and 0/10 patients after nicardipine 0.25, 0.5, 1.0, and 2.0 mg, respectively. In the patients who had SBP > 140 mm Hg, the vasodilator was initiated at an average (±SD) of 644 ± 450 s after nicardipine administration. Patients requiring vasodilator therapy during the study period were not analyzed separately because therapy was started at an average time that was beyond the acute effects of nicardipine. No serious adverse events judged to be directly related to nicardipine administration were encountered.
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Discussion
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Nicardipine administered as an IV bolus was found to be effective for acutely decreasing arterial pressure in a heterogeneous group of patients undergoing cardiac operations. The predominant action of nicardipine in anesthetized patients was a decrease in arterial pressure that was associated with only small changes in LV preload, afterload, and global systolic function. The decreases in SBP, DBP, and MAP after bolus nicardipine were greater than those reported in response to equivalent doses administered to awake patients (11). In contrast to awake patients, nicardipine administered to anesthetized patients did not increase HR and CO.
The pharmacodynamic actions of nicardipine administered as a single rapid IV bolus were consistent with a two-compartment pharmacokinetic model. The decrease in arterial pressure correlated with plasma drug concentrations. The effective duration of the initial decrease in arterial pressure was short and consistent with rapid redistribution of nicardipine from a small central compartment. The time course for recovery from the initial decrease in arterial pressure was consistent also with redistribution, followed by a slower rate of drug elimination. After redistribution, a smaller, but sustained decrease in arterial pressure was observed in the 2.0 mg dose group. The sustained response in this dose group could be explained by clinically significant plasma drug concentrations remaining after the initial redistribution phase. The duration and magnitude of this sustained response to nicardipine was proportional to the plasma drug concentration and determined by the rate of drug elimination. Sustained responses beyond the redistribution phase were either minimal or absent when the dose of nicardipine was 1.0 mg or less because plasma drug concentrations after redistribution were nearly undetectable after those doses.
In contrast to bolus administration, nicardipine administered by continuous IV infusion has been shown to exhibit a relatively slow onset of action and long duration of effect with a redistribution half-life of 17 min and a terminal elimination half-life of 12 h (16). In anesthetized patients, the antihypertensive action of nicardipine given as an IV infusion was found to persist for 22–88 min after discontinuation (17). The rapid onset of action and relatively short, but effective, duration of action that was achieved with bolus nicardipine suggested that this mode of administration was applicable for situations that require acute temporary decreases in arterial pressure during surgery.
The spectrum of hemodynamic changes generally observed in response to nicardipine administered to awake patients can be explained by its direct effects on the heart and vasculature in combination with reflex sympathetic nervous system activation from the decrease in arterial pressure (12). Attenuation of reflex sympathetic activity by general anesthesia would explain the absence of reflex tachycardia or increased CO after nicardipine administration. Attenuated reflex sympathetic activity could also explain why nicardipine caused a greater decrease in arterial pressure in anesthetized patients compared with awake patients. Fifty percent of patients in the study received preoperative ß-blocker therapy and any remaining ß-blocker effect that was present at the time of study could have also attenuated sympathetic responses. The observation that LV systolic function and ESWS changed only slightly despite significant decreases in arterial pressure was indirect evidence suggesting that nicardipine had a small negative inotropic action. A negative inotropic action of nicardipine was also demonstrated in a study that used LV pressure-volume and end-systolic elastance measurements to assess LV contractility in patients with heart failure despite increases in both the cardiac index and LV ejection fraction in response to the drug (18). The negative inotropic action of nicardipine has also been described in laboratory experiments using isolated cardiac papillary muscle preparations (12).
The CO and SvO of anesthetized cardiac surgical patients with a wide range of baseline ventricular function did not change in response to nicardipine. CO was unchanged even in patients who required phenylephrine to treat hypotension after drug administration. This finding suggested that nicardipine administered to anesthetized patients in doses ranging from 0.25 to 2.0 mg was safe for selectively decreasing the arterial pressure, even in patients with LV dysfunction in whom a decrease in CO would be undesirable. However, the absence of detectable increases in CO and significant decreases in ESWS suggested that nicardipine may not be an effective afterload reducing drug for treating low CO during general anesthesia. Although not tested, the negative inotropic action of nicardipine may manifest under conditions of increased LV afterload, as demonstrated in studies that examined the effect of phenylephrine to maintain or increase arterial pressure in response to hypotension caused by inhaled anesthetics (19,20).
Bolus IV nicardipine did not cause acute changes in LV preload. The gradual decrease in CVP, PAD, PAS, and EDA that was independent of the drug dose suggested that LV preload decreased during the period of study. The magnitude and time course of the decrease in preload were consistent with the onset of mild hypovolemia, probably as a consequence of continuing operative blood and fluid losses. The restriction of IV fluid administration during the period of study may have contributed to the development of mild hypovolemia. It was also possible that mild hypovolemia may have attenuated any increases in CO as a consequence of afterload reduction by nicardipine. Patients who became hypotensive after nicardipine exhibited a significant decrease in EDA of 1.1 ± 1.1 cm2 at time point 2 (45–150 s after nicardipine administration). Relative hypovolemia may have contributed to the development of hypotension after nicardipine in that selected group of patients.
It was difficult to completely isolate the effects of nicardipine on hemodynamic and LV function from dynamic changes inherent to a clinical setting. The timing of drug administration was chosen specifically to avoid the hemodynamic changes associated with manipulation of the heart, sternal closure, and surgical stimulation. In addition, fluid administration and anesthetic regimens were standardized during the period of study. Inclusion of a control group may have provided a means to adjust for asymmetry or drift in the self-controlled study design. However, quantifying pharmacodynamic actions over a range of drug doses, measuring plasma drug concentrations over time, and extrapolating the time course for recovery from drug responses accomplished our main objectives. The requirement to maintain SBP above 85 mm Hg by administering phenylephrine may have caused the maximum responses and times to achieve the maximum responses to be underestimated in the higher nicardipine dose groups. Despite this limitation, the need to administer phenylephrine for the treatment of hypotension permitted a means to examine the consequences of inadvertent drug overdose and the physiologic consequences of treatment with a vasopressor. A heterogeneous patient population was studied to provide results that would be representative of a typical clinical mix of patients. Restricting the study to a more homogeneous patient population may have decreased the standard error of measurements, but the drug-induced changes in arterial pressure were large and consistent enough to enable statistical comparisons.
In summary, nicardipine administered as an IV bolus dose was effective for rapidly and predictably decreasing arterial pressure during anesthesia in cardiac surgical patients. For IV bolus administration, initial nicardipine doses of 0.5–1.0 mg produced predictable decreases in the SBP of 32–36 mm Hg, decreases in the MAP of 21–24 mm Hg, a maximum response at approximately 60 s after drug administration, and a short duration of action because of rapid redistribution of the drug from a small central compartment.
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Acknowledgments
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The authors wish to acknowledge Timothy J. Gardner, MD, L. Henry Edmunds, MD, Michael A. Acker, MD, Joseph E. Bavaria, MD, and Charles L. Bridges, MD, for their assistance with the study.
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Footnotes
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The study was supported in part by a research grant from Wyeth-Ayerst Laboratories.
Presented in part at the annual meeting of the American Society of Anesthesiologists, Orlando, FL, October 1998.
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Accepted for publication June 29, 1999.
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Abstract
Introduction
