|Year : 2012 | Volume
| Issue : 2 | Page : 79-85
Effect of QTc interval on prediction of hypotension following subarachnoid block in patients undergoing cesarean section: A comparative study
Sampa Dutta Gupta1, Suddhadeb Roy2, Koel Mitra3, Sudeshna Bhar Kundu1, Sunanda Maji4, Aniruddha Sarkar5, Saikat Bhattacharya1, Chaitali D Roy6, Sreyasi Sen1, Mina Basu1
1 Department of Anaesthesiology, Institute of Post Graduate Medical Education and Research, SSKM Hospital, Kolkata, West Bengal, India
2 Department of Anaesthesiology, NRS Medical College, Kolkata, West Bengal, India
3 Department of Anaesthesiology, National Medical College, Kolkata, West Bengal, India
4 Department of Anaesthesiology, Midnapur Medical College, Midnapur, Kolkata, West Bengal, India
5 Department of Anaesthesiology, Medical College, Kolkata, West Bengal, India
6 Department of Gynaecology and Obstetric, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
|Date of Web Publication||17-Dec-2012|
Sampa Dutta Gupta
42 Lake Place, Kolkata
Source of Support: None, Conflict of Interest: None
Background: Previous studies have revealed that QTc interval is prolonged in pre-eclamptic parturients. Another study reflected the relationship between the sympathetic block and QTc interval. Subarachnoid block was safely administered in patients with severe pre-eclampsia. It has also been noticed that hypotension in response to spinal anesthesia is relatively less in pre-eclamptic patients than normal parturients.
Aim: To compare the QTc values in normal and pre-eclamptic term parturients and to establish whether any correlation exists between the QTc interval and the systemic hypotension following subarachnoid block.
Materials and Methods: Twenty-five pre-eclamptic patients (Group A) and 25 normotensive patients (Group B) were included in this study. QTc interval was recorded for each patient before subarachnoid block for cesarean section. Changes in arterial blood pressure and heart rate were measured in both the groups and compared.
Results: Baseline QTc was significantly higher in the pre-eclamptic group (Group A: 0.47 ± 0.11) with that of control (Group B: 0.36. ± 0.02). Significant fall in blood pressure was seen only in one group with QTc between 0.38 and 0.39 in Group A. Hypotension was significantly more in normotensive mothers (Group B). However, no statistical correlation could be drawn from this study between QTc interval and hypotension, although a trend toward increasing hypotension with decreasing QTc was present.
Discussion : The prolonged QTc intervals seen in pre-eclamptic patients may be due to the contributory effects of sympathetic hyperactivity, hypertension, and hypocalcemia secondary to underlying vasoconstriction. Decreased vagal control of heart in pre-eclampsia may have produced the difference in change in hemodynamic status between pre-eclamptic and normotensive parturient.
Conclusion: Any consistent correlation between QTc and hypotension following subarachnoid block could not be derived from this study. To achieve a statistical significance a larger sample size may be required.
Keywords: Hypotension, subarachnoid block, QTc
|How to cite this article:|
Gupta SD, Roy S, Mitra K, Kundu SB, Maji S, Sarkar A, Bhattacharya S, Roy CD, Sen S, Basu M. Effect of QTc interval on prediction of hypotension following subarachnoid block in patients undergoing cesarean section: A comparative study. J Obstet Anaesth Crit Care 2012;2:79-85
|How to cite this URL:|
Gupta SD, Roy S, Mitra K, Kundu SB, Maji S, Sarkar A, Bhattacharya S, Roy CD, Sen S, Basu M. Effect of QTc interval on prediction of hypotension following subarachnoid block in patients undergoing cesarean section: A comparative study. J Obstet Anaesth Crit Care [serial online] 2012 [cited 2022 Dec 4];2:79-85. Available from: https://www.joacc.com/text.asp?2012/2/2/79/104732
| Introduction|| |
The principal cardiovascular changes in pre-eclamptic patients are increased sympathetic hyperactivity and systemic vascular resistance. ,
Hypertension can be associated with sympathetic and cholinergic imbalance characterized by vagal withdrawal and relative sympathetic dominance. The changes in autonomic nervous system activity can directly affect the conduction systems, causing variations on QT interval length independently from heart rate and may confound the clinical assessment of cardiac repolarization time. , In our clinical practice, we frequently observe QTc interval prolongation in severe pre-eclamptic patients who require urgent cesarean delivery. 
Sympathetic blockade-induced hypotension may occur in up to 64%-100% of pregnant women given spinal anesthesia for cesarean delivery, especially when hyperbaric solutions are used. , Severely pre-eclamptic patients were previously believed to be at high risk of severe hypotension, with maternal and fetal consequences because of reduced plasma volume and because of the need to limit IV fluids to avoid iatrogenic pulmonary edema.
Till now, only few studies have compared the incidence and severity of hypotension in severely pre-eclamptic versus healthy parturients. ,,, In one of the recent studies, spinal anesthesia was safely administered in patients with severe pre-eclampsia. Furthermore, the incidence and the severity of hypotension was less in severely pre-eclamptic patients. 
On the other hand, subarachnoid block has been shown to modulate the effects of sympathetic overactivity, thereby changes in QTc in pre-eclamptic patients.  Therefore, we may postulate that, prolonged QTc intervals may have beneficial changes under subarachnoid block, and may reflect a correlation with hypotension along with the sympathetic blockade.
On the basis of a previous study, aim of this study is to correlate the QTc interval as a predictor of hypotension following subarachnoid block in patients undergoing cesarean section.
The objectives of this study were to compare QTc interval between pre-eclamptic and healthy parturient preoperatively, to measure the changes in blood pressure [systolic arterial blood pressure (SBP) and diastolic arterial blood pressure (DBP)] within the pre-eclamptic group and healthy pregnant group at 3, 5, 10, 20, 30, 60, and 120 min interval after subarachnoid block and to compare the same to preoperative value (baseline), and to compare the requirement of vasopressors between the two groups.
| Materials and Methods|| |
After obtaining approval from the institutional ethics committee and the written informed consent, 50 adult females, aged between 19 and 35 years, scheduled to undergo elective cesarean section under subarachnoid block were included in this prospective, parallel group study, conducted in SSKM Hospital, Kolkata, between October 2008 and April 2009.
Pregnant women having blood pressure more than 140/90 mmHg (pre-eclampsia group) beyond 20 weeks of gestation and treated only with oral methyldopa (250 mg bid)  were included in Group A. Healthy pregnant women with normal electrocardiograms (ECG) and no hypertension, proteinuria, or other systemic diseases were included in Group B (control).
Patients who were unwilling to participate in the study or having severe pre-eclampsia, pulmonary edema, intrauterine growth restriction, hypersensitivity to study drugs, contraindication to spinal anesthesia, or having any other systemic illness affecting QT interval were excluded from the study.
Sample size calculation was done using the PS Power and Sample size calculation software (version 2.1.30, February 2003). A pilot study was undertaken to find out the difference of mean QTc interval and the standard deviation. A difference of at least 70% in the QTc interval between the pre-eclamptic and normotensive pregnant women was accepted as significant. On the basis of these estimates, total sample size of 50 patients would be required to reject the null hypothesis with a power of 85% and a 5% probability of type I error.
All the patients were allotted according to their preoperative blood pressure into 2 groups, keeping 25 patients in each group (n = 25). Group A included the patients having preoperative blood pressure more than 140/90 mmHg and less than 160/110 mmHg beyond 20 weeks of gestation.
Group B included the patients having preoperative blood pressure more than 140/90 mmHg throughout gestation.
After a detailed preanesthetic assessment including evaluation of airway and fluid status, all the patients were premedicated with inj. metoclopramide 10 mg iv and inj. ranitidine 50 mg iv after securing intravenous access using 18 G intravenous cannula. All the patients were preloaded with Ringer lactate infusion of 10 mL/kg  administered over 20 min. Standard monitors were applied with an automatic blood pressure cuff, continuous five-lead ECG and pulse oxymetry.
The QT intervals were measured in lead II prior to institution of subarachnoid block manually from the onset of the QRS complexes to the end of the T wave (defined as the intersection of the isoelectric line and the tangent of the maximal downward limb of the T wave). Each registered measurement was a mean of two consecutive QT intervals. Heart rate was calculated from the three R-R intervals preceding the measured QT intervals. The measured QT interval was then corrected for heart rate, according to the formula of Bazette  : QTc = Measured QT/√RR interval (all measured in seconds). QT interval was accepted as "prolonged," when QTc values exceeded 440 ms. The two investigators who performed the results analysis were blinded to patient group.
Serum calcium (ionized and total in mg/dL), magnesium (Mg) and potassium (K) levels (in meq/L) were measured immediately before surgery. Subarachnoid block was instituted using a 25-gauge Whitacre needle at the L3-L4 interspace in the sitting position with 8 mg of 0.5% hyperbaric bupivacaine and 25 μg fentanyl. Thereafter, patients were placed in supine position with a wedge placed under the right hip to obtain a 15°-20° left uterine displacement. Onset of cephalad spread of analgesia was determined as loss of pin prick and block was confirmed at the level of T5-T6. All the patients were given 3 L/min of O 2 through nasal prongs.
Lactated Ringer's solution 5-6 mL/kg/h for 1 h and 500 mL hydroxyethyl starch (HES) 6% solution were infused together intravenously until completion of surgery. A decrease in SBP more than 20% below baseline after subarachnoid block was considered as hypotension. Hypotension was initially treated with fluid resuscitation. If the arterial blood pressure did not respond, phenylephrine was administered intravenously, titrated to the effect. Bradycardia (<60/min) was treated with 20 μg of atropine intravenously. Heart rate, respiratory rate, arterial blood pressure, SpO 2 % were noted preoperatively and every 10 min intraoperatively.
Oxytocin (5-10 units) was infused slowly intravenously after delivery of baby. The APGAR scores of the newborn were recorded as usual at 1 and 5 min, after delivery of baby.
QT interval is accepted as "prolonged," when QTc values exceeded 440 ms. Treatment arrangements which were kept ready for any precipitated arrhythmias included β-blockade, antibradycardia pacing, implantable automatic cardioverter-defibrillator (ICD). For analysis, height of block, total phenylephrine doses were noted. Systolic, diastolic, arterial blood pressures (mmHg), oxygen saturation (SpO 2 %), and heart rate changes (beats/min) were also recorded at preinduction, at the 5, 10, 20, 30, 60, and 120 min after initiation of the subarachnoid block.
All the raw data were entered into an Excel Spread sheet and analyzed using standard statistical software, such as "SPSS and Statistica." Categoric data were analyzed using Pearson's Chi-square test. Parametric data between groups were analyzed using unpaired t test and parametric data within the group were analyzed using paired t test. Nonparametric data within the group were compared by Wilcoxon rank sum test followed by post hoc test. The data were expressed as means ± SD. A P value of <0.05 was considered to indicate statistical significance.
| Results|| |
Total 53 patients were required to enroll for the study to keep total number of the patients of about 50 (25 in each group).
[Table 1] shows demographic profile and hemodynamic parameters between the two groups. Gestational age was significantly lower in pre-eclamptic group compared with the normal parturient (P < 0.05), mean weight revealed significantly higher in patients of Group A (68.38 ± 2), than Group B (55.19 ± 1.02). Baseline before subarachnoid block QTc interval (s) was significantly longer in Group A (0.47 ± 0.11) when compared with Group B (0.36 ± 0.02). Baseline SBP (Group A, 156.2 ± 14.3; Group B, 120.3 ± 7.27), DBP (Group A, 96.7 ± 10.2; Group B, 72.62 ± 5.62) before the induction of subarachnoid block were significantly higher in Group A compared with Group B. Baseline heart rate was insignificantly higher in Group A (104.29 ± 14.22) when compared with Group B (92.33 ± 9.62).
[Table 2] shows comparable onset time of motor block, APGAR score (Grade A, 9.32 ± 1.1; Grade B, 9.75 ± 1.4), maximum sensory block height (T6), uterine incision delivery time interval (Grade A, 2.4 ± 1.5; Grade B, 2.5 ± 1.4) between the two groups. Requirement of significantly less (P < 0.05) vasopressors revealed in Group A (53.02 ± 4.3 μg) compared with Group B (76.87 ± 3.2 μg). Group A patients required significantly less fluid (P < 0.05) (813 ± 43.5 mL crystalloids and 524 ± 50.3 mL colloids), in comparison with Group B (1634 ± 62.1 mL crystalloids and 557 ± 34.5 mL colloids).
[Figure 1] and [Figure 2] show statistically insignificant fall in SBP in Group A (146.62 ± 13.82 mmHg at 3 min, and 133.29 ± 15.84 mmHg at 5 min after block), and DBP (102.38 ± 5.28 mmHg at 3 min after, 91.53 ± 4.74 mmHg at 5 min after block) following subarachnoid block compared with baseline values (SBP, 156.2 ± 14.3 mmHg, DBP, 96.7 ± 10.2 mmHg).
|Figure 1: Modest fall in systolic blood pressure in pre-eclamptic group (146.62 ± 13.82 mmHg at 3 min after, 133.29 ± 15.84 mmHg at 5 min after)|
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|Figure 2: Modest fall in diastolic blood pressure (102.38 ± 5.28 mmHg at 3 min after, 91.53 ± 4.74 mmHg at 5 min after) in pre-eclamptic patients following subarachnoid block from the baseline values (SBP, 156.2 ±14.3 mmHg; DBP, 96.7 ± 10.2 mmHg)|
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There was a statistically significant fall in SBP (99.1 ± 9.46 mmHg at 3 min, and 100.67 ± 10.77 mmHg at 5 min after), and DBP (64.02 ± 8.38 mmHg. at 3 min after, 58.22 ± 6.42 mmHg at 5 min after) following subarachnoid block in Group B patients compared with baseline values (SBP, 120.3 ± 7.27; DBP, 72.62 ± 5.62).
The mean heart rate at different time intervals did not change significantly in Group A, whereas in Group B the change was significant decrease in heart rate, that is, 74.22 ± 14.49 at 3 min, 65.95 ± 12.39 at 5 min, and 69.49 ± 9.39 at 30 min intervals [Figure 3].
|Figure 3: Mean maternal heart rate at different time interval did not change signifi cantly in Group A, whereas in Group B there was signifi cant decrease in heart rate, that is, 74.22 ± 14.49 at 3 min, 65.95 ± 12.39 at 5 min, 69.49 ± 9.39 at 30 min interval|
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[Table 3] and [Figure 4] show that about 91% of patients of Group A had a QTc of 0.46-0.47 s, 7% of patients had QTc between 0.44 and 0.45 s, and the rest 2% had QTc between 0.42 and 0.43 s. In patients of Group B, 68% of patients had QTc between 0.38 and 0.39 s. Among the rest, 22% had QTc between 0.36 and 0.37 s, and 10% had 0.40-0.41 s.
|Table 3: Correlation between preoperative QTc and changes of SBP and mean BP at 5 min after initiation of subarachnoid block|
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|Figure 4: The QTc interval value was signifi cantly longer in the pre-eclampticgroup (Group A) when compared with that in the control group (Group B) before subarachnoid block (baseline value)|
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[Table 3] and [Figure 5] and [Figure 6] show that significant fall in SBP and DBP was seen only in patients with QTc interval between 0.38 and 0.39 (all patients in this subgroup belonged to Group A).
Hypotension, although present in other subgroups, did not reach statistical significance.
| Discussion|| |
Obstetric patients with pregnancy-induced hypertension require extra caution during anesthesia for cesarean section. In the absence of coagulopathy regional anesthesia is preferred in pregnancy-induced hypertension to avoid the risk of failed intubation due to severe edema of upper airway and to avoid life-threatening arrhythmias related to increased QTc for sympathetic stimulation related to intubation for general anesthesia.
The pre-eclamptic parturients show hyperactivity three times more commonly compared with normotensive parturients.  The prolonged QTc intervals seen in them may be due to the contributory effects of sympathetic hyperactivity, hypertension, and hypocalcemia secondary to pre-eclampsia. ,,
Contrary to the previous notion it has been seen from previous studies that not only spinal anesthesia can be safely used in the severely pre-eclamptic patient, , but also it might be more effective in reducing sympathetic activity compared with general anesthesia in pre-eclampsia. 
The main outcome of this study revealed in [Figure 1] and [Figure 2] is that a statistically significant fall in SBP and DBP after subarachnoid block in Group B patients was seen. Moreover, maximum patients in Group B with QTc 0.38-0.39 s had significant hypotension at 5 min following subarachnoid block.
Eva Eneroth-Grimfors and colleagues  observed decreased vagal control of the heart in pre-eclampsia. This decreased vagal control of heart in pre-eclampsia produce the difference in change in hemodynamic status between pre-eclamptic and normotensive parturient and may be the correct explanation for maintenance of hemodynamic stability of pre-eclamptic patients in comparison with normal parturient in spite of sympathetic blockade induced by subarachnoid block.
Sympathetic dominance increases the vascular tone and may contribute to hypertension in pre-eclamptic patients. The sympathetic outflow to vessels may be altered by subarachnoid block in both pre-eclamptic and healthy parturients. Pre-eclampsia is characterized by an increased production of numerous circulating factors with a potent pressor effect on one hand and by an increased sensitivity of blood vessels to pressor drugs because of endothelial damage on the other hand. These two phenomena contribute to the widespread vasoconstriction observed in pre-eclampsia,  which is only partially negated by subarachnoid block. Hence, pre-eclamptic patients maintain a relatively higher vascular tone, which is reflected as a limited fall in blood pressure following subarachnoid block compared with healthy parturients.
Previous study of Selda and coworkers also concluded that the prolonged QT interval was back to normal value within 5 min after spinal anesthesia. This might also reflect the relationship between the sympathetic block and QTc interval. 
Sympathetic overactivity is not only a single predictor of hemodynamic changes following subarachnoid block, as individual vagal tone, height of blocks, aortocaval compressions procedural-related factors all affect the post-block hypotension in combination. Till now, only a few studies have compared the incidence and severity of hypotension in severely pre-eclamptic versus healthy parturients. ,,,
In comparison to a pre-eclamptic parturient, the larger fetus of a healthy parturient may lead to increased risk of aortocaval compression. In addition, by dilating epidural blood vessels, the aortocaval compression could facilitate the cephalad spread of local anesthetics, leading to a higher upper level of spinal blockade in healthy parturients. Although the upper sensory levels were similar in both groups, the aortocaval compression may, at least partly, account for the increased incidence and severity of hypotension in the healthy parturients.
Therefore to conclude, QTc interval was significantly more in pre-eclamptic group than normotensives. Hypotension was also significantly more in normotensives, however, any correlation from the two observations cannot be firmly derived from this study as patients with either lesser value (0.36-0.37) or greater value (0.40-0.49) had insignificant hypotension.
However, one major limitation of our study may be the small sample size (50 patients), which may account for the inconsistent relationship of the QTc with the fall in BP in the normotensive women. Further studies in future with larger sample size may conclusively establish a more consistent relationship of QTc with the hypotension.
| References|| |
|1.||Fischer T, Schobel HP, Frank H, Andrea M, Schneider KT, Heusser K. Pregnancy-induced sympathetic overactivity: A precursor of preeclampsia. Eur J Clin Invest 2004;34:443-8. |
|2.||Ramanathan J, Benneth K. Pre-eclampsia: Fluids, drugs, and anesthetic management. Anesthesiol Clin North Am 2003;21:145-63. |
|3.||Magnano AR, Holleran S, Ramakrishnan R, Reiffel JA, Bloomfield DM. Autonomic nervous system influences on QT interval in normal subjects. J Am Coll Cardiol 2002;39:1820-6. |
|4.||Passino C, Franzoni F, Gabutti A, Poletti R, Galetta F, Emdin M. Abnormal ventricular repolarization in hypertensive patients: Role of sympatho-vagal imbalance and left ventricular hypertrophy. Int J Cardiol 2004;97:57-62. |
|5.||ACOG Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol 2002;99:159-67. |
|6.||Riley ET, Cohen SE, Macario A, Desai JB, Ratner EF. Spinal versus epidural anesthesia for cesarean section: A comparison of time efficiency, costs, charges, and complications. Anesth Analg 1995;80:709-12. |
|7.||Ueyama H, He YL, Tanigami H, Mashimo T, Yoshiya I. Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal anesthesia for elective Cesarean section. Anesthesiology 1999;91:1571-6. |
|8.||Ngan Kee WD, Khaw KS, Lee BB, Ng FF, Wong MM. Randomized controlled study of colloid preload before spinal anesthesia for cesarean section. Br J Anaesth 2001;87:772-4. |
|9.||Khaw KS, Ngan Kee WD, Wong M, Ng F, Lee A. Spinal ropivacaine for cesarean delivery: A comparison of hyperbaric and plain solutions. Anesth Analg 2002;94:680-5. |
|10.||Cunningham FG, MacDonald PC, Gant NF. Hypertension disorders in pregnancy. In: Cunningham FG, MacDonald PC, Gant NF, editors. Williams obstetrics. 18 th ed. Norwalk, CT: Appleton and Lange; 1989. p. 653-94. |
|11.||Sibai BM, Mabie BC, Harvey CJ, Gonzalez AR. Pulmonary edema in severe preeclampsia-eclampsia: Analysis of thirty-seven consecutive cases. Am J Obstet Gynecol 1987;156:1174-9. |
|12.||Aya AG, Mangin R, Vialles N, Ferrer JM, Robert C, Ripart J, et al. Patients with severe preeclampsia experience less hypotension during spinal anesthesia for elective cesarean delivery than healthy parturients: a prospective cohort comparison. Anesth Analg 2003;97:867-72. |
|13.||Visalyaputra S, Rodanant O, Somboonviboon W, Tantivitayatan K, Thienthong S, Saengchote W. Spinal versus epidural anesthesia for cesarean delivery in severe preeclampsia: A prospective randomized, multicenter study. Anesth Analg 2005;101:862-8. |
|14.||Dutta DC. Hypertensive disorder in pregnancy. Text book of Obstetrics. 7 th ed. Ch.17. Kolkata: New Central Book Agency LTD; 2011. p. 228. |
|15.||Mojica JL, Meléndez HJ, Bautista LE. The timing of intravenous crystalloid administration and incidence of cardiovascular side effects during spinal anesthesia: the results from a randomized controlled trial. Anesth Analg 2002;94:432-7. |
|16.||Greenwood JP, Scott EM, Stoker JB, Walker JJ, Mary DA. Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans. Circulation 2001;104:2200-4. |
|17.||Aya AG, Vialles N, Tanoubi I, Mangin R, Ferrer JM, Robert C, et al. Spinal anesthesia-induced hypotension: a risk comparison between patients with severe preeclampsia and healthy women undergoing preterm cesarean delivery. Anesth Analg 2005;101:869-75. |
|18.||Eneroth-Grimfors E, Westgren M, Ericson M, Ihrman-Sandahl C, Lindblad LE. Autonomic cardiovascular control in normal and pre-eclamptic pregnancy. Acta Obstet Gynecol Scand 1994;73:680-4. |
|19.||Sen S, Ozmert G, Turan H, Caliskan E, Onbasili A, Kaya D, The effects of spinal anesthesia on QT interval in preeclamptic patients. Anesth Analg 2006;103:1250-5. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3]