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Year : 2016  |  Volume : 9  |  Issue : 1  |  Page : 12-17

Comparative study between the effect of sevoflurane and ketamine-midazolam on the cardiac troponin I level and hemodynamic variables in pediatric therapeutic cardiac catheterization for pulmonic stenosis

Department of Anasthesiology, Mansoura University Hospital, Mansoura, Egypt

Date of Submission03-Apr-2014
Date of Acceptance19-May-2014
Date of Web Publication17-Mar-2016

Correspondence Address:
Hala M.S. Eldeen
Department of Anasthesiology, Mansoura University Hospital, Mansoura
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1687-7934.178873

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Congenital pulmonary stenosis is considered one of the most common cardiac anomalies in pediatrics. Percutaneous balloon dilatation is one method for its treatment, but it is usually associated with an increase in the cardiac troponin level.
Aims and objectives
The study was carried out to compare between the effect of sevoflurane and ketamine-midazolam on the level of cardiac troponin I as a specific marker for myocardial injury in children before and after therapeutic cardiac catheterization for pulmonic stenosis.
Patients and methods
Forty patients, up to 13 years old, undergoing cardiac catheterization were divided randomly into two groups: sevoflurane group (Gs) and ketamin-midazolam group (Gk-m). The standardized protocol for cardiac catheterization was maintained for all the patients. Serum samples were withdrawn at the start of - and 6 h subsequent to - the procedure for analysis of cardiac troponin I. Hemodynamic and oxygenation parameters were recorded at induction, T10, T20, and T30 minutes after induction. After recovery, sedation was assessed using the Ramsay Sedation Score.
Hemodynamic parameters, mean arterial blood pressure, heart rate, and cardiac index were significantly increased in Gk-m as compared with its basal values and with Gs. The serum cardiac troponin I was significantly increased after the procedure in both groups as compared with its basal value before the procedure. The increase in the cardiac troponin I was significantly higher in Gk-m than Gs (P < 0.001). The Ramsay Sedation Score showed a significant increase in Gk-m than Gs at all times postoperatively.
The use of sevoflurane as an anesthetic regimen for pediatric therapeutic cardiac catheterization for pulmonic stenosis is superior to the ketamine-midazolam combination as it is associated with a lower troponin I level, less myocardial injury, and greater hemodynamic stability.

Keywords: cardiac catheterization, cardiac troponin I, ketamine-midazolam, sevoflurane

How to cite this article:
Eldeen HM, Messeha MM. Comparative study between the effect of sevoflurane and ketamine-midazolam on the cardiac troponin I level and hemodynamic variables in pediatric therapeutic cardiac catheterization for pulmonic stenosis . Ain-Shams J Anaesthesiol 2016;9:12-7

How to cite this URL:
Eldeen HM, Messeha MM. Comparative study between the effect of sevoflurane and ketamine-midazolam on the cardiac troponin I level and hemodynamic variables in pediatric therapeutic cardiac catheterization for pulmonic stenosis . Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2023 Jan 27];9:12-7. Available from:

  Introduction Top

'Percutaneous balloon dilatation' is one method for the treatment of congenital pulmonary stenosis. Most pediatric interventional catheterization procedures are associated with myocardial injury, as evidenced by an increase in cardiac troponin I (cTnI) [1] .

A number of anesthetic regimens have been used for pediatric patients with congenital heart disease. Respective anesthetic goals would include managing shunt flow to balance systemic and pulmonary circulations, minimizing depression of ventricular function, avoiding increases in heart rate or ventricular contractility, maintaining normal sinus rhythm, and lowering pulmonary vascular resistance (PVRI) [2] .

The anesthesiologist plays a pivotal role in the evaluation and management of congenital heart disease by ensuring a calm, sedated child with stable hemodynamics for diagnostic as well as therapeutic cardiac catheterization. Perturbations of hemodynamic parameters can lead to changes in the patterns of intracardiac and extracardiac shunts, which may interfere with the evaluation of congenital heart disease. Maintaining spontaneous ventilation without supplemental oxygen is also desirable so that normal physiology is least altered. Anesthesiologists have sought intravenous agents that can produce rapid onset and offset of hypnosis without adverse effects on the cardiovascular and respiratory systems, and thus fill the gap in our armamentarium of intravenous anesthetic agents [3] .

Sevoflurane is known for its use as an inhaled induction agent and its superiority over the other anesthetic regimens in preserving cardiac output (CO) and contractility and maintaining normal heart rate and blood pressure; thus, it is an attractive choice [4] .

Ketamine produces dose-dependent central nervous system depression, leading to a dissociative anesthetic state characterized by profound analgesia and amnesia. If used appropriately, ketamine is associated with minimal cardiovascular and respiratory depression [5] .

Midazolam can cause transient mild respiratory depression and minimal hemodynamic effects in clinically recommended doses. In children, midazolam has been shown to produce tranquil and calm sedation, reduce separation anxiety, facilitate induction of anesthesia, and enhance ante-grade amnesia.

Ketamine and midazolam in combination are used because of the perceived ability to promote hemodynamic stability and produce analgesia and amnesia, even in patients with significantly limited cardiac reserve [6] .

The aim of this study was to compare the effect of sevoflurane versus ketamine-midazolam combination on the degree of myocardial damage and hemodynamic variables during the interventional catheterization with balloon dilatation in pediatric patients with pulmonary stenosis.

  Patients and methods Top

Following approval of the Institutional Ethics Committee and after obtaining written informed consent from the parents of patients, 40 patients were enrolled. The patients ranged in age from 1 to 13 years and they were subjected to interventional cardiac catheterization for balloon dilation of pulmonary stenosis in Mansoura Children University Hospital.

Patients were excluded from the study if they had a systemic right ventricle resulting in limitations in quantifying myocardial contractility by two-dimensional echocardiography. Similarly, patients with a functional single ventricle were excluded secondary to differences in loading conditions and difficulty comparing CO with patients with biventricular physiology. Patients receiving preoperative mechanical ventilation, opioids, or benzodiazepines were also excluded [7] .

Patients were randomized into one of two groups by selecting the first of a stack of prelabeled cards containing equal numbers of cards representing each group. They were thoroughly mixed to ensure randomization and maintained so that the group assignment of the next patient was not known until the card was actually drawn. The two groups were the sevoflurane group (Gs) and the ketamine-midazolam group (Gk-m). All patients received premedication with intravenous atropine 0.02 mg/kg and midazolam 0.02-0.05 mg/kg to achieve a sedated, but responsive state. Also, all patients were prehydrated with mixed glucose saline at a rate of 4-6 ml/kg.

In the operation theater, standard monitoring was applied in the form of ECG, pulse oximetry, and noninvasive blood pressure and baseline parameters were recorded. A baseline transthoracic echocardiogram was performed with the patient breathing room air. Anesthesia was then induced with either inhaled sevoflurane using calibrated vaporizers. Induction was performed with 8% sevoflurane for 2-3 min and then it was reduced gradually to 2% (Sevotec 5; Blease Medical Equipment Ltd, Chesham, UK) at a 10 l/min fresh gas flow (Ohmeda Excel 210; Ohmeda, Madison, Wisconsin, USA) or a ketamine-midazolam infusion for a duration of 1 min to produce a state of sedation, hypnosis, and analgesia with a starting dose of 2 mg/kg as a loading dose; then, it was maintained in infusion form and the mean total dose used was 1.13 ± 0.84 mg/kg/h (this is a result) for ketamine. For midazolam, 0.02-0.05 mg/kg was administered as a loading dose; then, it was maintained in infusion form and the mean total dose was 1.57 ± 1.03 mg/kg/h (this is a result). Any adjustment of dosage was in a concomitant bolus. Muscle relaxation was facilitated with atracurium 0.1 mg/kg and the trachea was intubated. Fractional inspired oxygen was maintained at 1.0 and end-tidal carbon dioxide was maintained at 30-35 mm g. The lowest possible mean airway pressure was maintained and the peak inspiratory pressure remained less than 25 cm H 2 O; a positive end-expiratory pressure of 2 cm H 2 0 and an inspiratory/expiratory ratio of 1 : 2-1 : 3 were used. Ketamine-midazolam induction and maintenance infusion rates were calculated on the basis of published pediatric pharmacokinetic data [8] .

The femoral artery and vein were accessed and a balloon-tipped catheter was floated into the pulmonary artery under fluoroscopic guidance for baseline hemodynamic measurements and balloon dilatation of pulmonary valve. HR, MAP, fractional shortening (FS), ejection fraction (EF), and cardiac index (CI) were measured and recorded immediately after induction of anesthesia (T0) and thereafter at 20 min (T20) and 40 min (T40) after induction of anesthesia. Right atrial pressure (RAP), arterial oxygen saturation (SaO 2 ), and PVRI were measured at 10 (T10), 20 (T20), and 30 (T30) min after induction of anesthesia.

Serum cardiac troponin I assay

A baseline serum sample was withdrawn before the procedure. If the baseline level was elevated above the normal range (normal range 0.1-0.2 ng/ml), patients were excluded from the analysis. A second serum sample was obtained 6 h after the procedure. Blood samples were collected from venous sheaths and introduced into tube collectors containing clot activators. Serum samples were centrifuged at 3000 rpm for ten minutes and the supernatant serum was removed and examined for cTnI. cTnI levels were determined quantitatively by a phase enzyme-linked immunosorbent assay using the Troponin I (Human Cardiac-Specific) Enzyme Immunoassay Test Kit (GenWay Biotech cTnI ELISA kit, GWB-83A61F; San Diego, USA) [9] .

At the end of the procedure, neuromuscular block was reversed with atropine 0.02 mg/kg and prostigmine 0.04 mg/kg and the patients were discharged from PACU when the Aldrete score was at least 9.

In the recovery room, the degree of sedation was assessed in both groups at 1-h intervals for 4 h using the Ramsay Sedation Score [10] .

Statistical analysis

The power of this clinical trial was retrospectively using G power analysis program version3 using post-hoc power analysis type Π error protection of 0.05 and effect size conversion of 0.8; a total sample size of 40 patients, 20 patients in each group, produced a power of 0.79.

All statistical calculations were carried out using SPSS version 8.0 (Knowledge Dynamics, Canyon Lake, Texas, USA). Data were tested for a normal distribution using the Kolmogorov-Smirnov test. Changes with time within a group were tested using the nonparametric Friedman test; time courses were compared between groups by analysis of variance for repeated measures. Statistical differences between groups were tested using Student's t-test or the Mann-Whitney U-test. Differences were considered significant if P less than 0.05

  Results Top

Each group included 20 patients and there was no significant difference in age, weight, and sex [Table 1] among patients of the two groups. Mean arterial blood pressure (MAP), and heart rate (HR), and CI increased significantly compared with their basal values in both groups; the increase in these parameters in the patients in the Gk-m group was also significant compared with patients of Gs [Figure 1]a and b. The cTnI was significantly increased after the procedure in both groups as compared with the basal values. The increase in cTnI was significantly higher in the patients in the Gk-m group than the patients in the Gs group (P < 0.05) [Figure 2]. The Ramsay Sedation Score showed a significant increase in Gk-m than Gs at all times postoperatively [Figure 3]. Both groups did not show a significant difference in, RAP, SaO 2 , and PVRI [Table 2]. Also, there were no significant changes in FS and EF in both groups [Figure 1]b.
Figure 1: (a, b) Hemodynamic variables before and after anesthesia. Data are expressed as mean ± SD. P < 0.05 is considered significant. *Significant in the same group. §Significant between groups. CI, cardiac index; EF, ejection fraction; FS, fractional shortening

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Figure 2: Cardiac troponin I level before and after cardiac catheterization. Data are expressed as mean ± SD. P < 0.05 is considered signifi cant. *Significant in the same group. §Significant between groups

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Figure 3: Ramsay Sedation score of two groups. Data are expressed as mean ± SD. P < 0.05 is considered significant. §Significant between groups

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Table 1 Characteristics of the patients in both groups

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Table 2 Right atrial pressure, pulmonary vascular resistance index, and systemic arterial O2 saturation before and after anesthesia in both groups

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  Discussion Top

The current study showed that therapeutic cardiovascular catheterizations for pulmonic stenosis can lead to myocardial damage and a marked increase in the cTnI concentration. Patients at higher risk of myocardial damage are those undergoing longer procedures and not necessarily patients with more challenging and difficult procedures. This means that the longer the duration of anesthesia and more the manipulation, the more the injury to the heart and higher the level of troponin in serum, whereas a shorter duration of anesthesia with less manipulation, even if difficult, is associated with less heart damage and less release of troponin. In human medicine, studies have shown that infants were also at a higher risk of myocardium damage with increased cTnI concentration after routine cardiac catheterization [1] . Moreover, the cTnI concentration showed a good correlation with the length of the cardiac catheterization procedure. However, Vydt et al. [11] postulated that none of the other procedural factors were evaluated including difficulty of the procedure, difficulty of anesthesia, or amount of contrast injected, which were correlated with a higher risk for myocardial damage. In contrast, in a previous study, Kannankeril et al. [12] showed that diagnostic catheterization did not have an effect on myocardial injury. They claimed that most of the diagnostic procedures did not cause an increase in cTnI above the lower limit of detection, and most interventional procedures were associated with an increase in cTnI, with radiofrequency ablation causing the greatest degree of increase. However, Basyal et al. [13] found that either diagnostic or therapeutic procedures had an impact on myocardial injury and carry the risk of subclinical myocardial damage in pediatric patients, but they studied cardiac troponin T levels as a marker instead of cTnI.

Increase in cardiac troponin in human patients can be a useful predictor of 6-month prognosis [14] . If an increased cTnI concentration helps to identify a high-risk subgroup of patients, this would allow for anticipation of complications and the need for close monitoring and therapeutic support. This is supported by another anesthesia mortality study, which indicated that increasing intended duration of the procedure and prolonged anesthesia time were associated with increased odds of anesthesia-related cardiac complications and death [15] .

Studies on the effects of anesthetic regimens on the degree of myocardial injury during cardiac catheterization are limited and contradictory.

In the present study, the induction dose of ketamine was 2 mg/kg and that of midazolam was 0.02-0.05 mg/kg, followed by the infusion of both drugs versus sevoflurane inhalation in the other group. This study had proved that the cTnI values are increased in the Gk-m group compared with the Gs group. These findings coincide with the fact that ketamine exerts a positive inotropic effect on the heart, increasing the cardiac work, myocardial contractility, heart rate, and systemic vascular resistance of the already injured heart [16] .

Ketamine has a long history in pediatric cardiac catheterization and has been used since 1971 [17] as it carries many potential advantages such as its safety, excellent sedation, and maintenance of airway reflexes and respiratory drive. The respiratory depression effect of ketamine is debatable. In addition, low-dose ketamine was found to have an antinociceptive action and provided analgesia in resistance cases [18] . However, it also has many disadvantages and some potential problems such as prolonged recovery time and emergence delirium. Moreover, it has some adverse hemodynamic effects including tachycardia, hypertension, and increased pulmonary vascular resistance [19] .

Benzodiazepines in general and midazolam in particular provide effective conscious sedation with minimal cardiovascular and respiratory side effects that can be reversed with flumazenil [20] . Furthermore, many studies that have used midazolam as an anesthetic induction agent found that it had an optimum cardiovascular profile, with minimal hemodynamic effects, together with multiple therapeutic benefits, such as sedation, hypnosis, and muscle relaxation [21] .

Ketamine and midazolam can be used as sedative agents for children during cardiac catheterization procedures. In low doses, both ketamine and midazolam can provide adequate sedation with a fast onset and a short duration of action without deleterious effects on either hemodynamic or respiratory functions. However, there are few previous reports on its use in pediatric catheterization [22] .

In addition, both groups did not show significant differences including FS, EF, RAP, SO 2 , and PVRI. These findings are in agreement with those of other studies [23] . In contrast, Zsigmond et al. [24] reported a decrease in oxygen saturation after intravenous ketamine administration in spontaneously breathing adults. It was found that MAP, HR, and CI in Gk-m were increased compared with their basal values and with Gs. This is in contrast to Jobeir et al. [6] , who proved that there was a decrease in heart rate and blood pressure after the administration of ketamine-midazolam. This may be because of the higher dose of ketamine; 2 mg/kg was used, followed by infusion, whereas Jobier et al. [6] used ketamine at a dose of 0.2-1 mg/kg with the same dose of midazolam 0.02-0.05 mg/kg in both studies. However, the differences were of no clinical relevance. Morray et al. [25] found no significant changes in BP and HR after administration of 2 mg/kg of ketamine. Furthermore, Green and Johnson [26] concluded that no significant cardiovascular complications or mortality could be attributed to ketamine administration. Fragen et al. [20] reported no hemodynamic changes after administration of 0.05 mg/kg midazolam intravenously to patients undergoing catheterization.

However, sevoflurane maintained hemodynamic stability in the present study. These findings are in agreement with those of Rivenes et al. [27] , who proved that the use of sevoflurane at different concentrations (at MAC 1 and 1.5) led to stabilization of HR, MAP, SO2, CO, EF, SF, and PVRI parameters during cardiac catheterization.

The Ramsay sedation score was significantly higher in the ketamine-midazolam group compared with the sevoflurane group. This finding could be attributed to the sedative effect of both ketamine and midazolam.

This is in agreement with Cotsen et al. [28] , who reported excellent results of sedation in 211 children younger than 10 years of age who underwent interventional radiological procedures and were sedated with ketamine (2 mg/kg intravenously or 3 mg/kg intramuscularly). Only minimal respiratory depression and cardiovascular changes occurred in these patients.

The limitations of this study are the lack of diversity and complexity of the cases, the lack of blinding, the fixed dosage of drugs, and a wide range in the age and weight of the patients.

  Conclusion Top

The use of sevoflurane as an anesthetic regimen for pediatric cardiac catheterization for pulmonic stenosis is superior to the ketamine-midazolam combination as it is associated with less myocardial injury and greater hemodynamic stability.

  Acknowledgements Top

Conflicts of interest

None declared.

  References Top

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]

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