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ORIGINAL ARTICLE  
Year : 2011  |  Volume : 14  |  Issue : 1  |  Page : 30-40
Preoperative ephedrine counters hypotension with propofol anesthesia during valve surgery: A dose dependent study


Department of Anaesthesia and Surgical ICU, King Fahd Hospital of the University, Al Khubar, Saudi Arabia

Click here for correspondence address and email

Date of Submission26-May-2010
Date of Acceptance28-Aug-2010
Date of Web Publication31-Dec-2010
 

   Abstract 

The prophylactic use of small doses of ephedrine may counter the hypotension response to propofol anesthesia with minimal hemodynamic changes. One hundred-fifty patients scheduled for valve surgery were randomly assigned into five groups (n = 30 for each) to receive saline, 0.07, 0.1, or 0.15 mg/kg of ephedrine, or phenylephrine 1.5 μg/kg before induction of propofol-fentanyl anesthesia. After induction, patient receiving ephedrine had higher mean arterial pressure, systemic vascular resistance (SVRI), cardiac (CI), stroke volume (SVI), and left ventricular stroke work (LVSWI) indices. Patients received 0.15 mg/kg of ephedrine showed additional increased heart rate and frequent ischemic episodes (P < 0.001). However, those who received phenylephrine showed greater rise in SVRI, reduced CI, SVI, and LVSWI and more frequent ischemic episodes. We conclude that the prophylactic use of small doses of ephedrine (0.07−0.1 mg/kg) is safe and effective in the counteracting propofol-induced hypotension during anesthesia for valve surgery.

Keywords: Cardiac anesthesia, ephedrine, hypotension, phenylephrine, propofol

How to cite this article:
El-Tahan MR. Preoperative ephedrine counters hypotension with propofol anesthesia during valve surgery: A dose dependent study. Ann Card Anaesth 2011;14:30-40

How to cite this URL:
El-Tahan MR. Preoperative ephedrine counters hypotension with propofol anesthesia during valve surgery: A dose dependent study. Ann Card Anaesth [serial online] 2011 [cited 2019 Oct 17];14:30-40. Available from: http://www.annals.in/text.asp?2011/14/1/30/74397



   Introduction Top


Rheumatic heart valve diseases are prevalent among the young people in Egypt secondary to the prevailing socioeconomic conditions. [1] The goal of anesthetic management of these patients is maintenance of sinus rhythm, normal systemic blood pressure, preload, coronary perfusion, and cardiac output.

Numerous studies suggested that propofol anesthesia is intuitively appealing for its simplicity, stability, and safety, permitting the rapid recovery of patients undergoing complex mitral and aortic valve surgery, [2],[3],[4],[5],[6] . Its use may be more beneficial than the use of midazolam. [5] However, its use for induction of anesthesia is often results in transient hypotension for about 5−10 min, [7],[8] which is mainly mediated with the decrease in sympathetic activity, direct vascular smooth muscle relaxation and direct negative inotropic effects. [9],[10] This may be detrimental to patients with valve diseases.

To counteract such adverse actions, phenylephrine may be useful for short-term blood pressure support during propofol anesthesia for cardiac surgery. However, its use increases the systemic vascular resistance and reduces cardiac output, and may result in transient impairment of left ventricular function and myocardial ischemia. [11]

Ephedrine has been shown to be a vasopressor agent for the treatment of hypotension in association with spinal and general anesthesia which is mostly mediated by b-stimulation rather than a-stimulation and indirectly by releasing endogenous norepinephrine from sympathetic nerves. [12] Although the prophylactic use of high doses of ephedrine range from 10 to 30 mg has demonstrated its usefulness in the treatment of propofol-induced hypotension, it may cause marked tachycardia. [13],[14] Other studies concluded that ephedrine in smaller doses of 0.03 and 0.07 mg/kg prevented hypotension due to propofol induction without significant increases in heart rate (HR) or dysrhythmias, which may be advantageous for the patients with valve diseases. [15],[16]

The author hypothesized that the prophylactic use of small doses of ephedrine may be better than the higher doses of ephedrine and phenylephrine in the prevention of propofol-induced hypotension after induction of anesthesia for valve surgery with minimal changes in hemodynamics, ST segment, and cardiac troponin I (cTnI).

The goal of the present study was to investigate the effects of three escalating doses of ephedrine, namely, 0.07, 0.1, and 0.15 mg/kg on the mean arterial blood pressure (MAP), systemic vascular resistance (SVRI), cardiac (CI), stroke volume (SVI), and left ventricular stroke work (LVSWI) indices,HR, ST segment, and cardiac troponin I changes as compared with placebo and phenylephrine, when used before propofol-fentanyl anesthesia in the patients undergoing elective valve surgery.


   Methods Top


One hundred-fifty American society of Anesthesiologists grade III−IV patients aged 18−55 years scheduled for elective valve surgery were included in this randomized double-blinded placebo-controlled study. An informed written consent was obtained from all the participants Local ethical committee approval for conducting the study was obtained. The study was registered in http://www.clinicaltrials.gov with a number of NCT01006863. Based upon our preliminary data, a priori power analysis indicated that indicated that 27 patients in each group would be a sufficiently large sample size to be adequate to detect a 25% changes in SVRI values, with a type-I error of 0.05 and 85% power. We added 10% more patients to account for the likelihood of patients dropping out during the study for whatever reasons. All surgeries were performed by the same group of surgeons. Participants were allocated randomly into five groups (n = 30 for each) to receive either saline [group 1], ephedrine 0.07, 0.1, or 0.15 mg/kg [groups 2, 3, and 4, respectively], or phenylephrine 1.5 μg/kg [group 5], 1 min before induction of anesthesia.

Patients with documented uncontrolled hypertension, ischemic heart disease, left ventricular ejection fraction less than 45%, severe pulmonary hypertension (mean pulmonary artery pressure > 45 mmHg), critical aortic stenosis (aortic valve area < 0.6 cm 2 and mean pressure gradient > 40 mmHg), peripheral vascular disease, thyrotoxicosis, neurological, hepatic, and renal diseases, pregnancy, re-do or emergency surgery, allergy to the study medications, those requiring preoperative inotropic, vasopressor, or mechanical circulatory or ventilatory support, and those who had electrocardiograph characteristics that would interfere with ST-segment monitoring, included baseline ST-segment depression, left bundle-branch block, atrial fibrillation, left ventricular hypertrophy, digitalis effect, QRS duration >0.12 s, as well as pacemaker-dependent rhythms, were excluded from the study.

All routine medications except angiotensin-converting enzyme inhibitors were continued until the morning of the operation. All patients were premedicated with 0.03 mg/kg IV midazolam and fentanyl 1 μg/kg before invasive instrumentation. All patients were monitored with pulse oximetry, non-invasive blood pressure and five leads electrocardiography (leads II and V5). Continuous ST-segment trends were electronically measured at the J-point + 60 milliseconds to exclude the T wave during the episodes of tachycardia. The tabulated and graphic ST-segment data were reviewed by two investigators who were not involved in the study and were blinded to the patient's group for significant ischemic responses. The latter were defined as reversible ST-segment changes from baseline of either ≥1 mV ST-segment depression or ≥2 mV ST-segment elevation lasting for at least 1 min. A radial artery catheter and a pulmonary artery catheter were placed under local anesthesia before induction. The final position of the pulmonary artery catheter tip was confirmed with portable chest X-ray film and pulmonary artery diastolic pressure > pulmonary artery occlusion pressure (PAOP). On-screen pressure tracing was used to determine end-expiration, and the PAOP was averaged over three respiratory cycles to eliminate respiratory artifacts. CI was measured by thermodilution using ice-cold injectate. Five measurements were performed, the lowest and highest readings were discarded, and the mean of the readings was recorded.

SVRI, SVI, and LVSWI were calculated by the following formulas: SVRI (dyne·s/cm 5·m 2 ) = mean arterial blood pressure (MAP) - central venous pressure (CVP) Χ 80/CI; stroke volume index (SVI; (ml/beat/m 2 ) = CI/heart rate; LVSWI (g·m/m 2 ) = SVI (MAP − PCWP) Χ 0.0136.

Intravenous infusion of 5−7 ml/kg of 6% hydroxyethyl starch 130/0.4 (Voluven, Fresenius Kabi, Bad Hombourg, Germany) was given before induction of general anesthesia when the baseline PAOP < 10 mmHg and/or CVP < 8 mmHg. End-tidal carbon dioxide monitoring and placement of a nasogastric tube, and rectal and nasopharyngeal temperature probes were done after induction of anesthesia.

Subjects were allocated randomly to five groups by drawing sequentially numbered sealed opaque envelopes containing a computer-generated randomization code. The subjects received intravenous injection of 0.1 ml/kg of a study solution containing either saline 0.9% solution [group 1] (n = 30), ephedrine 0.7 mg/ml [group 2] (n = 30), ephedrine 1 mg/ml [group 3] (n = 30), ephedrine 1.5 mg/ml [group 4] (n = 30), or phenylephrine 15 μg/ml [group 5] (n = 30). All study solutions were injected over 1 min at 1 min before induction of anesthesia. The placebo, ephedrine, and phenylephrine solutions were prepared in identical syringes labeled ''study drug'' by the local pharmacy department before induction of anesthesia. All staff in the operating room was unaware of the randomization code.

Anesthesia was induced with fentanyl 5 μg/kg and propofol 1−2.5 mg/kg to achieve state entropy (SE) (Datex-Ohmeda Division, Instrumentarium Corporation, Helsinki, Finland) < 50 and the difference between response entropy (RE) and state entropy (SE) < 10. Cisatracurium 0.2 mg/kg was given for muscle relaxation.

After endotracheal intubation, the lungs were ventilated with a mixture of oxygen in air to maintain an arterial carbon dioxide tension at 35−45 mmHg. Anesthesia was maintained with continuous infusions of propofol 4−6 mg/kg/h and fentanyl 0.025 μg/kg/min to maintain SE < 50 and SE-RE difference < 10. Cisatracurium 1−3 μg/kg/min was used to maintain suppression of the second twitch using a train-of-four stimulation. All patients received a slow injection of tranexamic acid 50 mg/kg before initiation of CPB.

Hemodynamic rescue treatment options were standardized to achieve target MAP and HR within 20% from the mean baseline values [Figure 1]. In the presence of hypotensive episodes (MAP decreased to ≤ 60 mmHg ≥ 2−3 min) and PAOP was ≤ 12 mmHg and/or CVP < 8 mmHg, 5−7 ml/kg of 6% hydroxyethyl starch 130/0.4 was given until adequate volume load was achieved. In the presence of MAP ≤ 60 mmHg, PAOP > 12 mmHg and/or CVP >10 mmHg, CI ≥ 2.2 l/min/m 2 , and SVRI ≤ 1500 dynesΧs/cm 5 /m 2 , repeated bolus doses of ephedrine 5 mg were given 5 min apart from each dose. When CI decreased to ≤ 2.2 l/min/m 2 despite PAOP > 12 mmHg and/or CVP > 10 mmHg and SVRI > 1500 dynesΧs/cm 5 /m 2 , boluses of epinephrine 5 μg were considered. In the presence of hypertensive episodes (MAP ≥ 20% from the mean baseline for ≥ 2−3 min) and tachycardia ≥ 20% from the baseline values for ≥1 min was treated with bolus doses of labetalol 20 mg. In the presence of hypertension and SVRI > 2500 dynesΧs/cm 5 /m 2 was treated with boluses of nitroglycerin 0.05 mg. Tachycardia ≥ 20% from the baseline values for ≥1 min was treated with boluses of esmolol 20 mg. Myocardial ischemia (ST-segment depression >1 mm) was treated with a nitroglycerin infusion or esmolol, or a combination.
Figure 1 :Intraoperative management of hemodynamics algorithm. MAP, mean arterial blood pressure; PAOP, pulmonary artery occlusion pressure; CVP, central venous pressure; CI, cardiac index; SVRI, systemic vascular resistance index.

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The cardiopulmonary bypass (CPB) tubings, oxygenator, and venous reservoir were primed. Heparin sodium 300 IU/kg was given after pericardiotomy to achieve celite-activated clotting time became higher than 480 s. Standard CPB technique was established with the ascending aorta cannula and the bicaval venous cannulae. During CPB, the non-pulsatile pump flow rate was 2.4 l/min/m 2 using a twin roller pump and a hollow fiber membrane oxygenator, perfusion pressure was 50−80 mmHg, arterial carbon dioxide tension was 35−40 mmHg, unadjusted for temperature (a-stat), arterial oxygen tension was 150−250 mmHg, and moderate systemic hypothermia (nasopharyngeal temperature 33−34ºC) was maintained. Myocardial viability was preserved with topical hypothermia and cold blood antegrade cardioplegia administered intermittently into the aortic root. During tricuspid valve surgery, the pulmonary artery catheter may be left in place, or temporarily pulled back into the right atrium, and then replaced by the surgeon.

Before separation from CPB, all patients were rewarmed (nasopharyngeal temperature 37ºC and rectal temperature 36ºC) and epinephrine, norepinephrine, and nitroglycerine infusions were used as needed after CPB according to the standardized author's center protocol. Intravenous fluids were administered when systolic blood pressure (SAP) < 90 mmHg and PAOP ≤ 12 mmHg and/or CVP < 8 mmHg. In the presence of SAP < 90 mmHg, PAOP > 12 mmHg and/or CVP > 10 mmHg, CI ≤ 2.2 L/min/m 2 and SVRI > 1500 dynesΧs/cm 5 /m 2 , dopamine (5−10 μg/kg/min), epinephrine (25−300 ng/kg/min), and intra-aortic balloon pump support were added sequentially. In the presence of SAP < 90 mmHg, CI > 2.2 l/min/m 2 , and SVRI < 1500 dynesΧs/cm 5 /m 2 , norepinephrine (25−100 ng/kg/min) was initiated. SAP > 130 mmHg was treated with nitroglycerin infusion (0.5−5.0 μg/kg/min). Heparin was neutralized after discontinuation of CPB with protamine sulfate.

After surgery propofol 1−2 mg/kg/h was used for sedation in the ICU and morphine 2-5 mg was used as needed for analgesia. Propofol infusion was discontinued and ventilator weaning was started once patients were awake and cooperative, hemodynamically stable without high doses of inotropic support, no severe arrhythmias, body core temperature >35.5ºC, bleeding <100 ml/h, urine output> 0.5 ml/kg/h, and arterial oxygen tension >100 mmHg with oxygen concentration <0.5.

Primary outcome variables included the changes in MAP, SVRI, and CI. Secondary outcome variables included the changes in HR, SVI, LVSWI, ST segment, cardiac troponin I, and the need for vasoactive drugs. The anesthesia providers were blinded to the study solution and were not involved in the assessment of the patients. Other anesthesiologists who were blinded to the study group and were not in the operative room performed the assessments of the studied patients.

MAP, SVRI, CI, SVI, HR, and LVSWI changes were recorded before (baseline), and 5 min after induction, 5, 10, and 15 min after endotracheal intubation; 15 min after skin incision and 15 min after sternotomy. The numbers and total time of intra-operative ischemic episodes were recorded in each group. Venous blood samples were drawn before, 3, 12, 24, and 48 h after CPB to measure cardiac troponin I. Blood samples were centrifuged at 3000 rpm for 10 min and serum samples stored at -20ºC. Two specific monoclonal antibodies were used to avoid the cross-reactivity with human skeletal muscle for the measurement of cTnI. The upper reference limits for cTnI in a control population was 0.6 μg/l. The number of patients who received rescue doses of nitroglycerine, ephedrine, atropine and esmolol during the entire surgical procedure, times from induction to intubation (I-T) and to skin incision (I-S), and from skin closure to extubation, ICU and hospital length of stays, and registered mortality within 30 days of surgery were recorded in each group.

Data were tested for normality using the Kolmogorov−Smirnov test. Repeated-measures analysis of variance was used for analysis of serial changes in the hemodynamic and cTnI data at different times after administration of study solution. Fisher exact test was used for categorical data. Repeated measure analysis of variance (ANOVA) was used for continuous parametric variables and the differences were then corrected by post-hoc Bonferoni test. The Kruskal−Wallis one-way ANOVA was performed for intergroup comparisons for the non-parametric values and post-hoc pairwise comparisons was done using the Wilcoxon rank sum t-test. Univariate analyses for the risk factors for propofol-induced hypotension were performed included EuroSCORE, left ventricular ejection fraction, treatment with ί-blockers, calcium channel blockers, and ACE inhibitors, and underlying valve pathology. Univariate predictors were examined in a stepwise manner into a multivariate logistic regression model, with entry and retention set at a significance level of P < 0.05 to assess the independent impact of this risk factor on the outcome. Data were expressed as mean (S.D.), number (%), or median [range]. A value of P < 0.05 was considered to represent statistical significance.


   Results Top


All 150 patients with rheumatic heart diseases completed the study: 30 each in the placebo (group 1), ephedrine 0.07 mg/kg (group 2), 0.1 mg/kg (group 3), and 0.15 mg/kg (group 4), and phenylephrine 1.5 μg/kg (group 5) groups. Patient characteristics including age, sex, weight, height, EuroSCORE, left ventricular ejection fraction, the number of diabetic patients and those receiving ί-blockers, calcium channel blockers, or ACE inhibitors, types of surgery, underlying pathology, times from endotracheal intubation to skin incision, and CPB, and aortic clamping, were similar in the five groups [Table 1].
Table 1 :Patients data in the placebo (group 1), ephedrine 0.07 (group 2), 0.1 (group 3) and 0.15 mg/kg (group 4), and phenylephrine 1.5 ìg/kg (group 5) groups

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Baseline hemodynamic variables included MAP, SVRI, CI, SVI, HR, and LVSWI showed no significant differences between the studied groups [Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6],[Figure 7], respectively). Changes in heart rate from baseline were significantly greater in group 4 than in the other four groups throughout the study period (P < 0.02) [Figure 6]. Patients received pre-induction ephedrine showed significantly higher MAP, SVRI, CI, SVI, and LVSWI values than in the placebo group throughout the study period (P < 0.001) [Figure 2],[Figure 3],[Figure 4],[Figure 5]; and [Figure 7], respectively. However, the patients received 0.15 mg/kg of ephedrine showed significantly higher MAP, SVRI, and LVSWI values than in groups 1, 2, and 3 (P < 0.001) [Figure 2];[Figure 3]; and [Figure 7], respectively. The prophylactic use of phenylephrine was associated with significant increases in the MAP values for 20 min compared with the groups 1, 2, and 3 (P < 0.01) [Figure 2]. Additionally, those received prophylactic phenylephrine showed significantly higher SVRI and lower CI, and SVI values than in the placebo and ephedrine groups for 20 min after its administration (P < 0.001) [Figure 3],[Figure 4],[Figure 5], respectively. LVSWI decreased significantly after the administration of phenylephrine than in the ephedrine groups (P < 0.01) [Figure 7].
Figure 2 :Mean arterial blood pressure [MAP] (mmHg) changes in the placebo (group 1) (n = 30), ephedrine 0.07 (group 2) (n = 30), 0.1 (group 3) (n = 30) and 0.15 mg/kg (group 4) (n = 30) and phenylephrine 1.5 μg/kg (group 5) (n = 30) groups. Data are presented as mean ± S.D. P < 0.05 significant compared with * group 1, and † groups 2 and 3.

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Figure 3 :Systemic vascular resistance index [SVRI] (dynes⋅sm2/cm5) changes in the placebo (group 1) (n = 30), ephedrine 0.07 (group 2) (n = 30), 0.1 (group 3) (n = 30) and 0.15 mg/kg (group 4) (n = 30) and phenylephrine 1.5 μg/kg (group 5) (n = 30) groups. Data are presented as mean ± S.D. P < 0.05 significant compared with * group 1, † groups 2 and 3, and § group 4.

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Figure 4 :Cardiac index [CI] (l/min/m2) changes in the placebo (group 1) (n = 30), ephedrine 0.07 (group 2) (n = 30), 0.1 (group 3) (n = 30) and 0.15 mg/kg (group 4) (n = 30), and phenylephrine 1.5 μg/kg (Group 5) (n = 30) groups. Data are presented as mean ± S.D. P < 0.05 significant compared with * group 1 and † groups 2, 3, and 4.

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Figure 5 :Stroke volume index [SVI] (ml/beat/m2) changes in the placebo (group 1) (n = 30), ephedrine 0.07 (group 2) (n = 30), 0.1 (group 3) (n = 30) and 0.15 mg/kg (group 4) (n = 30), and phenylephrine 1.5 μg/kg (group 5) (n = 30) groups. Data are presented as mean ± S.D. P < 0.05 significant compared with * group 1 and † groups 2, 3, and 4.

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Figure 6 :Heart rate [HR] (beat/min) changes in the placebo (group 1) (n = 30), ephedrine 0.07 (group 2) (n = 30), 0.1 (group 3) (n = 30) and 0.15 mg/kg (group 4) (n = 30), and phenylephrine 1.5 μg/kg (group 5) (n = 30) groups. Data are presented as mean ± S.D. P < 0.05 significant compared with * groups 1, 2, 3, and 5.

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Figure 7 :Left ventricular stroke work index [LVSWI] (gm⋅m/m2/beat) changes in the placebo (group 1) (n = 30), ephedrine 0.07 (group 2) (n = 30), 0.1 (group 3) (n = 30) and 0.15 mg/kg (group 4) (n = 30), and phenylephrine 1.5 μg/kg (group 5) (n = 30) groups. Data are presented as mean ± S.D. P < 0.05 significant compared with * group 1, † groups 2 and 3, and § group 4.

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The numbers and total time of intra-operative ischemic episodes were significantly higher in the patients received 0.15 mg/kg of ephedrine or phenylephrine than in the other groups (P < 0.02) [Table 2]. However, cardiac troponin I concentrations (cTnI) did not differ between the studied groups during the first 48 h after surgery [Table 3].
Table 2 :Clinical data in the placebo (group 1), ephedrine 0.07 (group 2), 0.1 (group 3) and 0.15 mg/kg (group 4), and phenylephrine 1.5 ìg/kg (group 5) groups

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Table 3 :Perioperative cardiac troponin I (cTnI) [ìg/l] changes in the placebo (group 1), ephedrine 0.07 (group 2), 0.1 (group 3) and 0.15 mg/kg (group 4), and phenylephrine 1.5 ìg/kg (group 5) groups

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The incidence of hypotensive episodes in the studied groups during propofol-fentanyl anesthesia for patients undergoing heart valve surgery showed in [Figure 8]. Eighty one percent of the patients in the placebo group developed hypotensive episodes with the use of propofol-fentanyl anesthesia [Figure 8]. The percentages of patients who developed hypotensive episodes were significantly less in the ephedrine and phenylephrine groups than in the placebo group [Figure 8]. The number of patients who received rescue doses of nitroglycerine was significantly higher in the ephedrine 0.15 mg/kg and phenylephrine groups than in the other groups during the first 20 min after induction of anesthesia (P < 0.05) [Table 2]. Eighty percent of the patients in the placebo group received rescue doses of ephedrine during the entire surgical procedure [Table 2].
Figure 8 :Percentage of patients who developed hypotensive episodes in the placebo (group 1) (n = 30), ephedrine 0.07 (group 2) (n = 30), 0.1 (group 3) (n = 30), 0.15 mg/kg (group 4) (n = 30), and phenylephrine 1.5 μg/kg (group 5) (n = 30) groups. Data are presented as median [range]. P < 0.05 significant compared with * group 1 and † groups 2 and 3

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There were no significant differences between the studied groups as regarding the number of patients who received rescue doses of atropine and esmolol, the number of delivered DC shocks, and the used doses of nitroglycerine, epinephrine, and norepinephrine after CPB, time to extubation, ICU, and hospital length of stays, and 30-day mortality rate [Table 2].

Multivariable logistic regression revealed that the risk factors for propofol-induced hypotension in the patients undergoing valve surgery included the preoperative EuroSCORE, LVEF < 50%, underlying aortic stenosis and mitral stenosis and those receiving angiotensin-converting enzyme inhibitors [Table 4].
Table 4 :Univariate and multivariate analysis for the risk factors for propofol-induced hypotension

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   Discussion Top


Fast-track propofol anesthesia has gained worldwide use in the patients undergoing valve surgery, [2],[3],[4],[5],[6] mainly because of its favorable pharmacokinetic properties, safety, and efficacy in the patients with both good and impaired ventricular function. [17],[18] However, there are concerns related to its detrimental vasodilating, and myocardial depressant effects in the patients with valvular heart diseases, [9],[10],[19] which may be related to the rate of its infusion. [20] On the other hand, the use of small doses of propofol 1−2 mg/kg and fentanyl 2−10 μg/kg was associated with non-significant decreases in blood pressure after induction of anesthesia for valve surgery. [2],[3] Similarly, we used small doses of propofol titrated according to Entropy variables for induction of anesthesia. The study period was extended beyond the time of sternotomy to assess the hemodynamic changes of both induction and maintenance of propofol anesthesia in the studied subjects.It was demonstrated in this study that propofol anesthesia shortened the time to extubation in the patients undergoing elective valve surgery; similar observations have been made by other workers too [19],[21] . However, 81% of these patients developed hypotensive episodes during anesthesia. Therefore, the prophylactic use of small doses of ephedrine ranged from 0.07 to 0.1 mg/kg before propofol anesthesia were associated with fewer hypotensive episodes, well-maintained MAP, SVRI, CI, SVI, and LVSWI, less need for rescue vasopressors, fewer ischemic episodes, and minimal changes in heart rate during valve surgery. The authors excluded the patients with critical aortic stenosis from our study to avoid the deleterious effects of propofol-induced hypotension on their outcome. There were no significant statistical differences between the studied patients as regarding their underlying valve pathology.

The authors selected three escalating doses of ephedrine, based upon the evidences provided by numerous publications who found that the doses of ephedrine ranges from 0.03 mg/kg to 0.2 mg/kg were useful in the prevention of propofol-induced hypotension during induction of anesthesia. [13],[14],[15],[16] Others concluded that smaller doses of ephedrine are not associated with adverse increases in HR or ischemic insults, [15],[16] which may be favorable for the unique patients with valve diseases.

In the present study, we found non-significant changes in heart rate with the prophylactic use of small doses of ephedrine (0.07−0.1 mg/kg) before propofol-fentanyl anesthesia. In contrast, others demonstrated excessive increases in heart rate after the administration of ephedrine 0.07 mg/kg for the prevention of propofol-induced hypotension in 12 patients underwent ambulatory anesthesia. [22],[23] This may be attributed to the fact that propofol being not supplemented by narcotics and the small number of studied population in that study. [22],[23] Furthermore, others reported significant short-lived increase in heart rate with the use of 0.07 or 0.2 mg/kg of ephedrine before propofol anesthesia. [14],[24],[25] This difference may due to the higher doses of fentanyl (total 11 μg/kg) used in our study for fast-tack cardiac anesthesia.

Ephedrine improves left ventricular contractility, without causing relevant changes of left ventricular afterload in the patients without cardiovascular diseases through a biphasic effect. Initially, it transiently decreases end-diastolic diameter and area (EDA) and increases area ejection fraction (EFA). After that, it increases MAP with restoration of EDA and EFA above their baseline values. [26] Similar increases in CI and SVI values with the use of ephedrine, which may be possibly mediated by ί-adrenergic stimulation was observed in this study. Other workers have found that ephedrine effectively improved blood pressure, right ventricular stroke volume and ejection fraction with the assistance for separation from cardiopulmonary bypass in the patients with normal preoperative ventricular function. [27] We demonstrated increases in LVSWI values with the use of escalating doses of ephedrine which may be explained with the concurrent increases in SVI and MAP values.

Additionally, the patients who received higher dose of ephedrine (0.15 mg/kg) before propofol anesthesia showed marked increases in SVRI, MAP, CI, SVI, and HR, and higher need for vasodilator therapy, with no differences in the patients who received their routine dose of beta-blocker on the day of surgery compared to those patients who were not receiving beta blockade.

The administration of high doses of ephedrine may be associated with significant ST-segment depression, non-Q-wave infarction, non-sustained ventricular tachycardia, and extended myocardial stunning secondary to induced multi-vessel coronary vasospasm, [28] and marked increases in oxygen demand secondary to the increases in heart rate and blood pressure values. [29],[30],[31] In our study, the use of 0.15 mg/kg ephedrine was associated with more frequent short-lived ischemic episodes with non-significant changes in cTnI levels secondary to the increases in HR, SVRI, and LVSWI values which may be resulted in increases in myocardial oxygen demand.

The authors used 1.5 μg/kg of phenylephrine based on the 95% effective dose (ED95) of intermittent intravenous boluses of phenylephrine for the prevention of spinal-induced hypotension during cesarean delivery which is at least 122 μg per 70 kg body weight (lower limit of the confidence interval). [32]

In the present study, the prophylactic use of phenylephrine before propofol anesthesia for valve surgery was associated with intense increases in SVRI and blood pressure, reductions in CI, SVI, and LVSWI and frequent ischemic episodes, which lasted for 20 min. Phenylephrine may cause short lived intense increase in the left ventricular afterload resulted in reduced cardiac output, stroke volume and LVSWI, which may be related to its short duration of action. [11] Similarly, others demonstrated reduced maternal cardiac output with the use of phenylephrine compared with ephedrine during spinal anesthesia for cesarean delivery. [33] In contrast, others failed to demonstrate significant changes in cardiac output after the administration of phenylephrine, which may be related to the small sample size in these studies. [34],[35]

We found that the preoperative EuroSCORE, LVEF < 50%, mitral and aortic stenotic valve lesions and preoperative treatment with angiotensin-converting enzyme inhibitors are independent risk factors for propofol-induced hypotension during valve surgery.

The present study included 150 young patients with underlying rheumatic heart diseases, which are prevalent among this age group in the author's country. However, the older patients with intrinsic coronary artery disease could have an unknown but major effect as well on the hemodynamic response to vasopressors before propofol anesthesia.

The author's study has important limitations. First, they did not test the effects of prophylactic doses of ephedrine higher than 0.15 mg/kg on propofol-induced hypotension, because their uses may produce increases in heart rate and ischemic insults which are not desirable in the patients suffering from mitral and aortic stenotic valve lesions. [13],[14] Second, the use of PAOP for the assessment of volume responsiveness may be inaccurate in the patients with stenotic lesions. However, Krishnamoorthy and colleagues found good correlation of PAOP with left atrial pressure even in the presence of pulmonary arterial or

venous hypertension before and after balloon mitral valvuloplasty. [36] Third, thermodilution-derived CI may be lower than the actual values in the presence of tricuspid regurgitation. However, there was non-significant difference between the numbers of the patients with tricuspid valve disease in the studied groups. Fourth, LVEF estimation may be tricky in the patients with regurgitant lesions, because it is sensitive to changes in left ventricular loading conditions. However, other indices of systolic function appear to be less than the EF, which appears to be the most clinically relevant index of left ventricular systolic function useful in these patients. [37]

Further multi-center studies may be needed to validate the safety of prophylactic use of ephedrine and phenylephrine in the prevention of propofol-induced hypotension in the patients undergoing valve and coronary artery bypass surgery.

In conclusion, the prophylactic use of small doses of ephedrine (0.070.1 mg/kg) is safe and effective in the counteraction of propofol-induced hypotension during anesthesia for valve surgery.


   Acknowledgments Top


The author would like to express his great appreciation to Dr. Mohamed Islam, Dr. Ibrahim Abdul Basseer, Dr. Osama Seyam, and Dr. Hani Taman (Staff Anesthesiologists, Department of Anesthesiology, Mansoura University Hospitals, Mansoura, Egypt); for their great help in the performance, and in gathering data for this study.

 
   References Top

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Correspondence Address:
Mohamed R El-Tahan
Anesthesiology Department, University of Dammam, Dammam, P.O. 40289 Al Khubar 31952
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9784.74397

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

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