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ORIGINAL ARTICLE
Year : 2016  |  Volume : 19  |  Issue : 1  |  Page : 115-120

The effect of colloid preload versus prophylactic ephedrine administration on QTc intervals during cesarean delivery: A randomized controlled study


1 Department of Anesthesiology and Reanimation, Faculty of Medicine, Ataturk University, Erzurum, Turkey
2 Department of Obstetrics and Gynecology, Nenehatun Hospital, Erzurum, Turkey

Date of Acceptance10-Aug-2015
Date of Web Publication12-Jan-2016

Correspondence Address:
A N Aksoy
Department of Anesthesiology and Reanimation, Faculty of Medicine, Ataturk University, Erzurum
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1119-3077.173710

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   Abstract 

Aim: We aimed to investigate the effect of colloid infusion immediately before the spinal anesthesia, and the prophylactic intravenous (IV) infusion of ephedrine after injection of intrathecal bupivacaine on hemodynamic parameters, QT, The QT interval corrected for heart rate (QTc), and dispersion of QTc (QTcDisp) intervals in women undergoing the elective cesarean section. Materials and Methods: Sixty women scheduled for elective cesarean delivery with spinal anesthesia were allocated randomly to receive either IV fluid preloading with 0.5 L of 6% w/v hydroxyethyl starch solution immediately before the spinal anesthesia (colloid group, n = 30) or prophylactic IV infusion of 15 mg ephedrine (diluted with 10 ml saline, n = 30) over 1-min period after the injection of intrathecal bupivacaine (ephedrine group). Electrocardiography (ECG) tracings were recorded before anesthesia procedure at baseline (T0), 5 min (T1), 10 min (T2), 30 min (T3), 60 min (T4), and 120 min (T5) after the spinal anesthesia. Systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO2) values were also recorded at the same time intervals. Results: There were no significant differences between groups with respect to MAP, HR, SpO2, QT, and QTc intervals at any time points (P > 0.05). When compared with the colloid group, the QTcDisp interval at T1was significantly longer in the ephedrine group (P < 0.05). Conclusion: Both methods have similar effects on the ECG and hemodynamic parameters during cesarean section. So, both methods may be used in patients undergoing elective cesarean delivery under spinal anesthesia.

Keywords: Anesthesia, cesarean section, colloid, electrocardiography, ephedrine, spinal


How to cite this article:
Tör I H, Aksoy M, Aksoy A N, Ahıskalıoglu A, Ince I, Kürsad H. The effect of colloid preload versus prophylactic ephedrine administration on QTc intervals during cesarean delivery: A randomized controlled study. Niger J Clin Pract 2016;19:115-20

How to cite this URL:
Tör I H, Aksoy M, Aksoy A N, Ahıskalıoglu A, Ince I, Kürsad H. The effect of colloid preload versus prophylactic ephedrine administration on QTc intervals during cesarean delivery: A randomized controlled study. Niger J Clin Pract [serial online] 2016 [cited 2019 Oct 15];19:115-20. Available from: http://www.njcponline.com/text.asp?2016/19/1/115/173710


   Introduction Top


Electrocardiographic abnormalities such as new arrhythmias and premature atrial or ventricular beats may occur during pregnancy due to pregnancy induced constitutional, hormonal, and hemodynamic changes. Also, cardiovascular system changes that occurred during pregnancy (a decrease in peripheral vascular resistance increases in circulating blood volume, end diastolic volume, heart rate [HR], and cardiac output) may contribute the development of an arrhythmia.[1],[2]

In the electrocardiographic (ECG) tracing, the time between the start of the Q wave and the end of the T wave is defined as the QT interval. The QT interval demonstrates the total period of the left ventricle's depolarization and its repolarization. Normally, the QT interval is 0.36–0.44 s and the QT value more than 0.44 s are named prolonged QT.[3] Prolonged QT may be inherited or acquired. Various drugs such as volatile anesthetics, opioids, vasopressor drugs, and muscle relaxants; electrolyte abnormalities such as hypokalemia, hypocalcemia, and hypomagnesemia have been found to be associated with the QT prolongation.[4],[5],[6] The QT prolongation increases the risk of ventricular arrhythmias, polymorphic ventricular tachycardia (Torsades de pointes), and ventricular fibrillation.[7],[8]

The methods of regional anesthesia are commonly used for cesarean operations in developed countries.[9],[10],[11] In our clinic, spinal anesthesia is the most widely used anesthetic technique for elective cesarean section deliveries.[12] There are some advantages of spinal anesthesia, including avoiding the risks of general anesthesia, allowing the mother to be awake, providing minimal newborn depression, providing postoperative pain control, and reducing maternal mortality. However, short-term or prolonged maternal hypotension may occur in patients undergoing cesarean section with spinal anesthesia due to the loss of sympathetic tone, a reduction in systemic vascular resistance, and pregnancy-induced aortocaval compression.[9],[10] The QT interval length is affected by these changes in autonomic nervous system activity.[13] It was reported that the spinal anesthesia provokes a significant QTc (the QT interval corrected for HR) interval prolongation in patients undergoing elective orthopedic surgery under spinal anesthesia.[14]

We hypothesized that avoiding hypotension associated with spinal anesthesia for a cesarean section may prevent the QT interval changes during surgery and postoperatively. Therefore, this prospective randomized study was designed to compare the effects of the conventional technique of preloading with 0.5 L of 6% w/v hydroxyethyl starch (HES) solution immediately before the spinal anesthesia with the prophylactic intravenous (IV) infusion of 15 mg ephedrine (diluted with 10 ml saline) over 1-min period after injection of intrathecal bupivacaine on hemodynamic parameters and QT interval length in women undergoing elective cesarean section.


   Materials and Methods Top


This study was approved by the Ethics Committee of Ataturk University, Medical Faculty, Erzurum, Turkey and written informed consent was obtained from all the participants. Between January 2013 and March 2014, 64 women with singleton pregnancy with the age of 18 and 40 years, American Society of Anesthesiologists physical status I and II and scheduled for elective cesarean delivery with spinal anesthesia were included in this study. Patients in labor, with body mass index (BMI) >30 kg/m 2, a history of a cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, preeclampsia, electrolyte abnormalities, congenital or acquired prolonged QT interval, severe anemia, smoking, alcohol consumption, fetus in breech presentation, known fetal abnormalities, and contraindications to spinal anesthesia such as coagulation disorder and infection at the puncture site were excluded from the study.

Premedication was not given to any of the patients. All operations were performed between 08.00 a.m. and 12.00 p.m. Before their transfer to the operating room, patients were assigned to one of two groups (colloid group and ephedrine group) using a computer generated random number table (n = 32, for each group). Vascular access was obtained with an 18-gauge cannula. The standard monitorization (Datex-Ohmeda, Helsinki, Finland) and standard 12-lead ECG (Cardiofax, Nihon Kohden, Tokyo, Japan) were provided for all patients. ECG tracings were recorded before the anesthesia procedure at baseline (T0), 5 min (T1), 10 min (T2), 30 min (T3), 60 min (T4), and 120 min (T5) after spinal anesthesia and printed at a paper speed of 50 mm/s and amplification of 0.1 mm mV/mm. Systolic blood pressure (SBP), diastolic blood pressure, mean arterial pressure (MAP), HR, and peripheral oxygen saturation values were also recorded in the same time intervals.

Patients in the colloid group received a preload of 0.5 L of 6% w/v HES solution over 15–20 min immediately before the initiation of spinal anesthesia. Patients in ephedrine group did not receive fluid preload. After skin infiltration with 2% lidocaine, 26-gauge Quincke's needle was inserted through the L2-3/L3-4 intervertebral space of the patient in sitting position. Once the free flow of cerebrospinal fluid was obtained, isobaric bupivacaine 0.5% 8.5 mg (Marcaine; AstraZeneca plc, London, UK) was injected intrathecally. Then, the patient was placed in the supine position with at least 15° of left lateral tilt to prevent aortocaval compression and sensory block levels were identified by the pinprick test at 1, 5, and 10 min of spinal anesthesia. The surgery was initiated when the satisfactory block level was provided. Oxygen was administered at 3–4 L/min via a nasal cannula until delivery. Patients in ephedrine group received IV 15 mg ephedrine (diluted to 10 ml using saline) over a 1-min period immediately after injection of intrathecal bupivacaine. Hypotension was defined as a decrease of 30% or more in SBP compared with preoperative values. Hypotension was primarily treated with fluid replacement and 5 mg IV ephedrine were administered when necessary. Hypertension was defined as an increase of >30% or more in SBP compared with baseline values. Bradycardia was defined as HR <45 beats/min and 0.5 mg IV atropine were planned for cases of bradycardia. Patients in both groups received saline solution as maintenance fluid at the rate of 5 ml/kg/h during surgery. After delivery, all patients received IV infusion of 20 IU oxytocin (in lactated Ringer's solution of 1000 ml) over 30 min.

Sociodemographic information (age, BMI, and the week of gestation), duration of surgery (the time from the start of the surgical incision to the completion of surgery), highest sensory block level, anesthetic complications, and the number of patients required ephedrine or atropine during surgical procedure were recorded.

All the standard 12-lead ECG traces were analyzed by one author independently. He was blinded to the study groups and the times of the ECG recordings. HR was calculated using mean RR time. The QT interval was defined as the interval between the beginning of the QRS complex and the end of the T wave. Each recorded QT and RR measurements was an average of the three consecutive RR and QT intervals from standard lead II. When the U waves were present, the end of the T wave was defined as the curve between the T and U waves. The QT interval corrected for HR (QTc) was identified using the Bazett formula (QTc (ms) = QT measured/√RR).[15] Maximum (QTc-max) and minimum QTc (QTc-min) intervals were recorded. The difference between the QTc-max and QTc-min intervals was defined as QTc dispersion (QTcDisp).

The minimum sample size required for this study was calculated based on the Owczuk et al.'s study [14] using the Russ Lenth's power and sample size calculation application.[16] Twenty-three patients in each group were needed to demonstrate a mean difference of 30 ms for the QTc interval between two study groups with a power of 80% and alpha of 5%.

Data were analyzed using the SPSS software version 12.0 (SPSS Inc., Chicago, IL, USA) and calculated as the mean and the standard deviation, P < 0.05 was considered as significant. The Kolmogorov–Smirnov test was used to assess the normal distribution of data. If data were not normally distributed, comparisons were determined using the Mann–Whitney U-test. The comparison of variables at different times within groups such as QTc intervals and hemodynamic parameters was conducted using a paired sample t-test with the Bonferroni's posthoc comparisons tests. The independent samples t-test was used in the comparison of variables between groups. Fisher's exact test was used to compare the percentage values. The Chi-square test was used to compare the categorical variables between groups.


   Results Top


The course of patients through this study is shown in [Figure 1]. There were no significant differences among groups in terms of age, BMI, the week of gestation, sensory block level at 5 min, and surgery duration [Table 1]. Satisfactory anesthesia was provided to all patients within 5–20 min of intrathecal bupivacaine injection. The indications for a cesarean section of cases were a previous cesarean section, repeated cesarean section, and cephalopelvic disproportion. There were no significant differences between groups in terms of sensory block levels at 5 min after spinal anesthesia (P > 0.05) [Table 1]. While both groups had similar MAP values at all times, MAP values at T1, T2, T3, T4, and T5 time points showed a statistical change compared to the baseline values in both groups (P < 0.001, for all) [Figure 2]. In both groups, no patient had a severe hypotension requiring ephedrine during surgery. When the groups were compared with respect to mean HR values at all times, there were no statistically significant difference between or within groups. Bradycardia requiring atropine was not observed in any patients in both groups [Figure 3]. No patient in both groups had hypertension during surgery.
Figure 1: CONSORT flow diagram. The course of patients through this study was shown

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Table 1: Clinical characteristics of study groups

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Figure 2: The variation in mean arterial pressure values in study groups. *P < 0.001 for both groups, when compared to baseline values. *P < 0.001, as compared with T1, T2 and T3 time points within both groups

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Figure 3: The variation in heart rate after spinal anesthesia in study groups

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As shown in [Table 2], there were no significant differences between groups in terms of the QT and QTc intervals at any time points (P > 0.05). In the ephedrine group, the QTc intervals were longer at T2 and T3 as compared to baseline (P < 0.001). In the colloid group, the QTc intervals were longer at T1, T2, and T3 time points as compared to baseline (P < 0.001). The QTc-max and QTc-min intervals at T3 were significantly longer in the ephedrine group, as compared to the colloid group (P < 0.05). In both groups, the QTc-max intervals were longer at T1, T2, T3, and T4 as compared to baseline (P < 0.001). In the ephedrine group, the QTc-min intervals were longer at T2, T3 andT4 as compared to baseline (P < 0.001). In the colloid group, the QTc-min intervals were longer at T1, T2, T3, and T4 time points as compared to baseline (P < 0.001). When compared with the colloid group, the QTcDisp interval at T1 was significantly longer in the ephedrine group (P < 0.05). In the ephedrine group, the QTcDisp intervals

were longer at T1,T2, T3, and T4 as compared to baseline (P < 0.001). In the colloid group, the QTcDisp intervals were longer at T3 as compared to baseline (P < 0.001).
Table 2: QT, QTc, QTc-max, QTc-min and QTcDisp intervals in study groups

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   Discussion Top


In the present study, we investigated the effect of prophylactic ephedrine infusion and colloid preloading on the QT interval changes during spinal anesthesia for cesarean section. Although, we observed a statistically significant prolongation in the QTc intervals at 10 and 30 min after spinal anesthesia in both groups, as compared with baseline values; the QT, QTc interval, HR and MAP values were similar between groups.

Owczuk et al.[14] investigated the influence of spinal anesthesia on the QTc interval in patients undergoing elective orthopedic surgical procedures. They reported statistically significant lengthening in the QTc interval values after 1, 3, 5, and 15 min of adequate blockade, and significant decreases in systolic, diastolic, and mean arterial blood pressure values from the 3rd min of blockage when compared with the baseline values. Similar to their results, we found statistically

significant differences with respect to MAP and QTc interval values at 10 and 30 min after spinal anesthesia when compared to baseline separately in both groups. Also, there were no differences between groups as to MAP and QTc intervals at 10 and 30 min after spinal anesthesia. These prolongations may be associated with the effect of lumbar sympathetic blockage of spinal anesthesia. On the other hand, it was shown that local anesthetics such as bupivacaine and levobupivacaine may cause arrhythmias, ECG changes, and profound cardiac depression.[17] Supporting findings were observed in a previous study of Dogan et al.,[18] where they had compared the effect of bupivacaine and levobupivacaine for spinal anesthesia on QT interval during caesarean section. They reported prolonged QTc interval values at 38 min after spinal anesthesia as compared to baseline separately in both groups. In contrast to our results, Guillon et al.[19] reported that the QTc intervals are not modified by spinal anesthesia during cesarean section in healthy women. Nevertheless, they administered prophylactic vasopressor IV infusion (ephedrine 195 mg/h or phenylephrine 2.5 mg/h) to all patients and they measured the QTc intervals at 1, 3, and 5 min after spinal anesthesia induction. In the present study, QTc intervals were measured before anesthesia procedure at baseline, 5, 10, 30, 60, and 120 min after the spinal anesthesia.

QTcDisp is defined as the difference between the QTc-max and QTc-min intervals, and it was reported to be useful in the assessment of arrhythmia risk.[20] In the current study, QTcDisp at T1 was found to be longer in ephedrine group compared to the colloid group. Also, while only QTcDisp interval at T3 was statistically different in the colloid group, QTcDisp intervals at T1,T2, T3, and T4 were statistically different in the ephedrine group compared with baseline values. These QTcDisp intervals changes in ephedrine group may explain the sympathomimetic activity through α and β adrenergic receptors of ephedrine.[21] Indeed, it was reported that an increase in sympathetic activation has critical roles in the cardiac action potential repolarization.[22] Also, Jing et al.[23] revealed that ephedrine induces both the tachycardia and the change in QTc interval with the normal clinic concentration.

Oxytocin is an uterotonic agent and is used to reduce blood loss after fetal delivery. The administration of IV bolus oxytocin following fetal delivery was found to be associated with an increase in QTc intervals in patients undergoing cesarean section under spinal anesthesia.[18] In the present study, IV bolus oxytocin was not administered to any patients in both groups, and we used slow IV infusion of oxytocin. We observed statistically significant QTc interval changes at 30 min (almost fetal delivery duration) after spinal anesthesia compared with baseline values in both groups, and these changes were not different between groups.

This is the first study comparing prophylactic ephedrine infusion and colloid preloading regarding QT interval changes in patients undergoing a cesarean section. There was a limitation in the present study. We did not compare the effects of different doses of ephedrine on QT intervals. We know that spinal anesthesia may lead to a short-term or prolonged hypotension due to the loss of sympathetic tone.[9],[10] And the QT interval is affected by the changes in autonomic nervous system activity.[13] Simon et al.[24] reported that the administration of a single bolus of IV ephedrine with doses of either 15 or 20 mg is sufficient to prevent spinal hypotension. So, we used ephedrine in a dose of 15 mg. Nevertheless, future studies researching the effects of ephedrine in doses of 10, 15, and 20 mg at the time of cardiac depolarization and repolarization and also including a greater number of patients are required.


   Conclusion Top


The preloading with the HES solution immediately before spinal anesthesia and the prophylactic IV ephedrine administration immediately after the injection of intrathecal bupivacaine have similar effects on the QT and QTc intervals, and hemodynamic parameters during cesarean section. Both methods can be preferred depending on the patient's clinical and laboratory findings and the preference of the anesthesia team in patients undergoing elective cesarean section with spinal anesthesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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Guillon A, Leyre S, Remérand F, Taihlan B, Perrotin F, Fusciardi J, et al. Modification of Tp-e and QTc intervals during caesarean section under spinal anaesthesia. Anaesthesia 2010;65:337-42.  Back to cited text no. 19
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]


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