Background:Despite preventive strategies, hypotension is the most common complication of spinal anesthesia in cesarean section.
Objectives:The aim of this study was to assess the effect of glucose-containing crystalloid infusion on maternal hemodynamic status after spinal anesthesia for cesarean section.
Methods:In this prospective, randomized, double-blind clinical trial, 80 parturients undergoing elective cesarean section with spinal anesthesia were studied. In group A (n = 40) ringer with 1% glucose solution (10 gr glucose in 1000 mL ringer) and in group B (n = 40) only ringer solution infused before and after spinal anesthesia. Demographic data, hemodynamic change, complications and their treatments, maternal blood sugar level and neonatal APGAR (appearance, pulse, grimace, activity and respiration) score, intraoperative fluid, duration of surgery, and anesthesia were recorded in the two groups.
Results:The incidence of hypotension in group A was significantly lower than group B (27.5% vs 75%) (P = 0.002). Other complications (sustained hypotension, nausea, pallor, and shivering were significantly lower in parturients of the group A (P < 0.05). Maternal blood sugar (BS), before and after surgery, was not significantly different in the two groups (P = 0.207 and P = 0.239, respectively). There was no statistically significant difference in the APGAR score of neonates at the 1st and 5th minutes of the birth between the two groups (P = 0.076).
Conclusions:It seems that adding 1% glucose to crystalloid solution improves the hemodynamic status and decreases post-spinal anesthesia complications without significant changes in the maternal blood sugar level and APGAR score of neonates.
Regional anesthesia is one of the most common methods used during cesarean section (1). Hypotension, due to sympathetic block, is the most common side effect of spinal anesthesia in cesarean section and can lead to severe injuries (2-4). Even with preventive approaches, its prevalence is 80% - 100% in parturients undergoing cesarean section (5-7).
Hypotension decreases cerebral blood flow and may lead to side effects such as nausea, vomiting, decreased consciousness, as well as respiratory and cardiac depression in the mother. Moreover, severe and sustained hypotension can reduce the uteroplacental blood flow and ultimately lead to fetal acidosis and depressed APGAR score (8-12).
Although crystalloid fluid preload is widely used to prevent and treat post-spinal anesthesia hypotension, its efficacy is not certain (9, 13-18). Studies suggest that rapid crystalloid infusion before spinal anesthesia causes rapid redistribution of fluid and secretion of atrial natriuretic peptide (ANP). Therefore, its peripheral vasodilation effect causes a rapid elimination of the preloaded volume. Administration of colloidal fluids for the prevention of post-spinal anesthesia hypotension is more effective than crystalloid fluids in some studies (13-15).
In a study, maternal cardiac output stability with colloidal solutions infusion (hydroxyethyl starch containing 1% dextrose) was better than crystalloid solutions. However, Yorozu et al. (17), did not find a statistically significant difference in comparison of preloading infusion of colloids vs ringer lactate in the prevention of post-spinal anesthesia hypotension in parturients undergoing cesarean section.
Today, it is advisable to use oral or intravenous glucose-containing solutions to provide maternal and fetal energy and accelerate the progress of labor (18, 19). In a review study, preoperative carbohydrate administration improved recovery, accelerated gastrointestinal function, and reduced hospitalization time without postoperative side effects in patients undergoing various surgical procedures (20).
Glucose decreases maternal and fetal ketone bodies that are produced due to mother’s long-term fasting during delivery (21).
Intravenous glucose-containing solutions may also reduce fetal arterial acidemia and hypercarbia and increase maternal and embryonic energy (22). It seems to prevent post-operative hypoglycemia and may not affect the APGAR (appearance, pulse, grimace, activity, and respiration) scores and the acid-base balance of the umbilical artery (23).
Recent studies have shown the benefits of administering colloidal fluid containing glucose 1% before or immediately after spinal anesthesia to improve the hemodynamic status of the mother under cesarean section (24-27). Although some satisfactory effects of perioperative glucose administration have been demonstrated in some studies, there is no certain data to indicate the effect of glucose-containing crystalloid infusion on the maternal hemodynamic. The current study was hypothesized to evaluate these effects.
After approving the ethics committee of Tabriz University of Medical Sciences, the proposal has been registered in the Iranian center of the clinical trials (IRCT201702077013N17; http://www.irct.ir).
In this double-blind randomized prospective clinical trial, the prevalence of hypotension after spinal anesthesia was considered as a primary outcome. According to Arora et al. (27), the prevalence of hypotension in the control group was 67%, with α = 0.05 for the first type of error and power of β = 0.80 for detecting the difference of 32% reduction in the incidence of hypotension after spinal anesthesia, 80 specimens were estimated. A total of 80 pregnant women in the age ranges of 18 - 40 years, with American Society of Anesthesiologists (ASA) class I, with singleton term (> 37 weeks of gestational age) pregnancy who were candidates for the elective cesarean section with spinal anesthesia enrolled in the study.
They were randomly allocated into two groups of A and B using Random list software. A total of 40 parturients enrolled in each group. The informed consent form was achieved from all women before beginning the study. Demographic charectristics including age, weight, height, body mass index (BMI), cause of cesarean section, and number of pregnancies were recorded.
The exclusion criteria were body mass index (BMI) > 35 kg/m2, any coexisting systemic disease, contraindications of spinal anesthesia, history of glucose intolerance, drug history of glucose metabolism affecting drugs, bleeding more than 1000 cc, and fetal problems.
In the operating room, the standard monitoring was done including non-invasive blood pressure (NIBP), electrocardiogram (ECG), and pulse oximetry (SPO2). The parturients in group A (n = 40) received 1% glucose containing ringer serum, which was prepared by adding 10 g of glucose to 1000 mL ringer before and during operation. Group B (n = 40) only received the ringer serum.
In both groups, before spinal anesthesia, 8 mL/kg intravenous bolus serum infused in 15 minutes and after spinal anesthesia, infusion continued by 15 - 20 mL/kg/hr until the end of surgery.
In both groups, spinal anesthesia was performed in sitting position, in L3 - L4 or L4 - L5 intervertebral space by needle quincke 25 gaged. A total of 2.2 mL solution (10 mg (2 mL) Hyberbaric bupivacaine 0.5% plus 20 micrograms fentanyl) injected intrathecally.
Surgical incision was performed when the sensory block level of T4 was achieved by the same surgeon in all patients.
An anesthesiologist managed the anesthesia and the second anesthesiologist who was not aware of the study group collected the data. Intraoperative fluid volume, duration of surgery, and anesthesia and maximum sensory block level were recorded.
Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and heart rate (HR) were recorded until the end of the operation. SPO2 and ECG were monitored continuously.
All the spinal anesthesia induced complications including hypotension, bradycardia, nausea and vomiting, agitation, shivering, pallor, respiratory depression, and decreased consciousness were recorded.
In case of hypotension (SBP < 100 mmHg or decrease of more than 25% of baseline), 5 - 20 mg ephedrine or 50 - 200 μg phenylephrine were injected intravenously. Sustained hypotension defined as failure to respond to a single dose of vasopressor. Bradycardia (heart rate less than 50 beats/min) was treated with a dose of 0.02 mg/kg atropine. A total of 1 mg of midazolam was injected to treat agitation and 5mg metoclopramide was injected for treating nausea and vomiting.
Respiratory support was done in case of decreased consciousness and respiratory depression (SPO2 < 90%).
The 1st and 5th minutes APGAR score were recorded. In addition to the above, the total dose of vasopressors and maternal blood sugar (BS) values before and after the surgery were recorded.
Data were analyzed by SPSS 16 software. All data were reported as means ± standard deviation (SD) for quantitative variables and percentages for categorical variables (28). One-way ANOVA and independent two-sample t-test were used to confirm the effect of glucose-containing crystalloid infusion on maternal hemodynamic status. A dependent two-sample t-test was used for comparison of the variables in the two groups. P < 0.05 was considered statistically significant.
Overall, 80 parturients participated in this study. A total of six women were excluded from the study due to a BMI of more than 35 kg/m2, 4 women due to high bleeding, whom were replaced with 10 parturients that were enrolled in the study, and finally 80 pregnant women were examined with 40 in each group.
Demographic characteristics (age, weight, height, BMI) and cause of cesarean delivery and number of pregnancies were not different between the two groups (Table 1).
|Group A (n = 40)||Group B (n = 40)||P Value|
|Age (y)a||29.20 ± 5.88||29.95 ± 5.89||0.571|
|Weight (kg)a||75.17 ± 9.30||77.23 ± 11.85||0.389|
|Height (cm)a||160.50 ± 5.46||160.35 ± 5.78||0.905|
|BMI (kg/m2)a||29.19 ± 3.39||29.93 ± 3.57||0.340|
|Cause of cesarean section (%)b||0.344|
|History of cesarean||80||72.5|
|Number of pregnancies (%)b||0.102|
There were no significant differences in intraoperative fluid infusion volume, duration of surgery, and anesthesia and maximum sensory block level (Table 2).
In the analysis of hemodynamic variables, the incidence of hypotension in all women was 51.3%. Hypotension occurred in 11 (27.5%) patients in group A and 30 (75%) in group B. Incidence of hypotension in group A was significantly lower than group B (P = 0.002). There was a statistically significant difference in hypotension incidence in time intervals of 2 (P = 0.006), 4 (P = 0.001), 6 (P = 0.005), and 8 minutes (P = 0.024) after spinal anesthesia between the two groups (Table 3).
|Time||Group A (n = 40)||Group B (n = 40)||P Value|
There was a significant difference in average systolic blood pressure in time intervals of 2 (P = 0.015), 4 (P = 0.001), and 6 minutes (P = 0.006) after spinal anesthesia between the two groups. In other time intervals, there were no significant differences (P > 0.05) (Figure 1).
There was a significant difference in average diastolic blood pressure in time intervals of 4 (P = 0.009) and 6 minutes (P = 0.020) after spinal anesthesia between the two groups. In other time intervals, there were no significant differences (P > 0.05) (Figure 2).
There was a significant difference in average mean blood pressure in time intervals of 4 (P = 0.003) and 6 minutes (P = 0.010) after spinal anesthesia between the two groups. In other time intervals, there were no significant differences (P > 0.05) (Figure 3).
Bradycardia occurred in one patient (2.5%) in group A and one patient (2.5%) in group B (P = 0.500). There was no significant difference in heart rate in all time intervals after spinal anesthesia between the two groups (P > 0.05) (Figure 4).
Blood oxygen saturation decreased below 90% only in one patient in group B. There was no significant difference in average basic oxygen saturation and in other time intervals after spinal anesthesia between the two groups (P > 0.05) (Figure 5).
In the evaluation of the incidence of other complications of spinal anesthesia, sustained hypotension, nausea, pallor, and shivering incidence were significantly higher in group B. There were no statistical differences in the incidence of other complications between the two groups (Table 4).
|Group A (n = 40)||Group B (n = 40)||P Value|
|Nausea and vomiting||2.4||26.2||0.002|
|Treatment of complicationsb|
|Ephedrine (mg)||5.11 ± 2.26||9.66 ± 3.51||0.002|
|Phenylephrine (μg)||50.00 ± 0.00||66.66 ± 25.81||0.145|
|Atropine (mg)||22.33 ± 36.95||0.50 ± 0.00||0.660|
|Midazolam (mg)||1.00 ± 0.00||1.06 ± 0.25||0.620|
|Metoclopramide (mg)||0||5.00 ± 0.00||-|
|Respiratory support (%)a||0||2.4||0.910|
In assessing the drug used to treat the complications, the used dose of ephedrine (P = 0.002) was significantly higher in group B. Only one woman needed respiratory support who was in group B (Table 4).
There was no significant difference in blood sugar level before anesthesia and after the end of surgery in the two groups (P > 0.05). However, both groups had increased blood glucose levels after surgery (P = 0.001). The 1st and 5th minute APGAR score of neonates was not significantly different between the two groups (P = 0.076). Only 3 cases (8.9%) of the total neonates had a 1st min APGAR score of 7 or less than 7, all of which were in group B. None of the neonates had a 5th min APGAR of less than 8 (Table 5).
|Group A (n = 40)||Group B (n = 40)||P Value|
|Maternal blood sugar(mg/dL)|
|Before the surgery||86.45 ± 12.55||89.92 ± 11.72||0.207|
|After the surgery||92.73 ± 12.83||95.94 ± 11.10||0.239|
|Neonatal APGAR score|
|1 min||8.97 ± 0.15||8.79 ± 12.73||0.059|
|5 min||10||9.86 ± 0.47||0.076|
In this study, the incidence of hypotension in all time intervals in group A was lower than group B (P = 0.002), which indicates improvement of hemodynamic status in the group A. Consequently, complications such as sustained hypotension, agitation, nausea, and pallor were lower in group A, and less ephedrine was used to treat complications in this group.
Nette et al. reported that glucose-containing solutions could maintain a blood volume more than isovolemic solutions (29).
Gosmanov et al. (30), also studied the effects of dextrose and intra-lipid infusion and found that dextrose infusion increased blood pressure and the vascular effects that were observed with dextrose infusion depended on blood glucose concentrations.
Fathi et al. (4), in a study on patients undergoing femoral fracture surgeries who received Hetastarch or Ringer’s lactate solutions, showed that Hetastarch was not significantly more effective in compensation of hypotension induced by spinal anesthesia.
Wilson et al. (31), reported that glucose infusion does not affect the incidence of hypotension and does not facilitate its treatment. Smith et al. (20), Showed that infusion of glucose-containing solution can reduce the duration of hospitalization.
Yorozu et al. (17), did not succeed in finding positive effects of HES in preventing hypotension and reducing ephedrine doses for treatment of hypotension after spinal anesthesia, however, they found that intravenous fluid demand in use of colloid was less than ringer lactate. They reported that this effect was related to the higher viscosity of HES compared to lactate ringer, partly due to the presence of 1% dextrose in a HES solution (17).
In a study by Brenck et al. (32), that examined the risk factors for hypotension in pregnant women undergoing cesarean section, age, body mass index, and block level were effective factors in the prevalence of hypotension. However, in the present study, there was no statistically significant relationship between the above factors and the occurrence of hypotension.
By administering high-energy solutions during the perioperative period, glucose-based solutions have been shown to eliminate the effects of fasting and maintain liver glycogen and reduce the stress responses and increase the insulin sensitivity of the tissues (18, 19).
In the present study, although blood sugar levels increased after surgery, this change was within the physiological range and was not significant. Fukuda et al. (22), concluded that administration of 1% glucose, with ringer acetate to women undergoing cesarean section with epidural anesthesia, does not cause maternal hyperglycemia and it properly maintains the levels of blood glucose in newborns.
Yatabe et al. (23), concluded that administration of 1% glucose solution in women undergoing cesarean section with combined spinal-epidural is effective in preventing hypoglycemia in neonates.
There was no significant difference between the 1st and 5th min of APGAR scores in both groups. In the Yorozu et al. and Smith et al. studies, there was no significant difference in the outcome of newborns after administration of glucose-containing solutions, which indicates that the glucose-containing crystalloid infusion has no negative effect on the outcome of neonates (17, 20).
The findings of the present study showed that glucose-containing crystalloid infusion can reduce post-spinal anesthesia hypotension and its subsequent complications. Maternal blood sugar level and neonatal outcome were not significantly different in the two groups and it shows the safety of glucose-containing crystalloid administration.
Imani F, Entezary SR, Alebouyeh MR, Parhizgar S. The maternal and neonatal effects of adding tramadol to 2% lidocaine in epidural anesthesia for cesarean section. Anesth Pain Med. 2011;1(1):25-9. doi: 10.5812/kowsar.22287523.1271. [PubMed: 25729652]. [PubMed Central: PMC4335753].
Kinsella SM, Carvalho B, Dyer RA, Fernando R, McDonnell N, Mercier FJ, et al. International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. Anaesthesia. 2018;73(1):71-92. doi: 10.1111/anae.14080. [PubMed: 29090733].
Zieleskiewicz L, Noel A, Duclos G, Haddam M, Delmas A, Bechis C, et al. Can point-of-care ultrasound predict spinal hypotension during caesarean section? A prospective observational study. Anaesthesia. 2018;73(1):15-22. doi: 10.1111/anae.14063. [PubMed: 28986931].
Fathi M, Imani F, Joudi M, Goodarzi V. Comparison between the effects of ringer's lactate and hydroxyethyl starch on hemodynamic parameters after spinal anesthesia: A Randomized Clinical Trial. Anesth Pain Med. 2013;2(3):127-33. doi: 10.5812/aapm.7850. [PubMed: 24244923]. [PubMed Central: PMC3821133].
Chestnut DH, Polley LS, Wong CA, Tsen LC. Chestnut's obstetric anesthesia: principles and practice. 4th ed. Philadelphia: Elsevier Health Sciences; 2009.
Quan ZF, He HL, Tian M, Chi P, Li X. Influence of lateral decubitus positioning after combined use of hyperbaric and hypobaric ropivacaine on hemodynamic characteristics in spinal anesthesia for caesarean section. Int J Clin Exp Med. 2014;7(12):5669-74. [PubMed: 25664088]. [PubMed Central: PMC4307535].
Yurtlu BS, Hanci V, Okyay RD, Bostankolu SE, Kayhan GE, Hakimoglu, S , et al. Effects on hypotension incidence: hyperbaric, isobaric, and combinations of bupivacaine for spinal anesthesia in cesarean section. Turk J Med Sci. 2012;42(2):307-13. doi: 10.3906/sag-1010-1258.
George RB, McKeen DM, Dominguez JE, Allen TK, Doyle PA, Habib AS. A randomized trial of phenylephrine infusion versus bolus dosing for nausea and vomiting during Cesarean delivery in obese women. Can J Anaesth. 2018;65(3):254-62. doi: 10.1007/s12630-017-1034-6. [PubMed: 29209926]. [PubMed Central: PMC5856192].
Ayorinde BT, Buczkowski P, Brown J, Shah J, Buggy DJ. Evaluation of pre-emptive intramuscular phenylephrine and ephedrine for reduction of spinal anaesthesia-induced hypotension during Caesarean section. Br J Anaesth. 2001;86(3):372-6. [PubMed: 11573527].
Bhat MA, Buchh VN, Gurcoo SA, Nazir I, Qazi S. Comparison between phenylephrine and ephedrine in preventing hypotension during spinal anesthesia for cesarean section. J Obst Anaesth Critical Care. 2012;2(2):92. doi: 10.4103/2249-4472.104734.
Wang X, Xu JM, Zhou F, He L, Cui YL, Li ZJ. Maternal position and development of hypotension in patients undergoing cesarean section under combined spinal-epidural anesthesia of intrathecal hyperbaric ropivacaine. Med Sci Monit. 2015;21:52-8. doi: 10.12659/MSM.892224. [PubMed: 25557016]. [PubMed Central: PMC4292763].
Hirose N, Kondo Y, Maeda T, Suzuki T, Yoshino A. Relationship between regional cerebral blood volume and oxygenation and blood pressure during spinal anesthesia in women undergoing cesarean section. J Anesth. 2016;30(4):603-9. doi: 10.1007/s00540-016-2165-6. [PubMed: 27011334].
Nishikawa K, Yokoyama N, Saito S, Goto F. Comparison of effects of rapid colloid loading before and after spinal anesthesia on maternal hemodynamics and neonatal outcomes in cesarean section. J Clin Monit Comput. 2007;21(2):125-9. doi: 10.1007/s10877-006-9066-4. [PubMed: 17265094].
Rout CC, Rocke DA, Levin J, Gouws E, Reddy D. A reevaluation of the role of crystalloid preload in the prevention of hypotension associated with spinal anesthesia for elective cesarean section. Anesthesiology. 1993;79(2):262-9. [PubMed: 8192733].
Teoh WH, Sia AT. Colloid preload versus coload for spinal anesthesia for cesarean delivery: the effects on maternal cardiac output. Anesth Analg. 2009;108(5):1592-8. doi: 10.1213/ane.0b013e31819e016d. [PubMed: 19372341].
Tamilselvan P, Fernando R, Bray J, Sodhi M, Columb M. The effects of crystalloid and colloid preload on cardiac output in the parturient undergoing planned cesarean delivery under spinal anesthesia: a randomized trial. Anesth Analg. 2009;109(6):1916-21. doi: 10.1213/ANE.0b013e3181bbfdf6. [PubMed: 19923521].
Yorozu T, Morisaki H, Kondoh M, Zenfuku M, Shigematsu T. Comparative effect of 6% hydroxyethyl starch (containing 1% dextrose) and lactated Ringer's solution for cesarean section under spinal anesthesia. J Anesth. 2002;16(3):203-6. doi: 10.1007/s005400200025. [PubMed: 14517641].
Shrivastava VK, Garite TJ, Jenkins SM, Saul L, Rumney P, Preslicka C, et al. A randomized, double-blinded, controlled trial comparing parenteral normal saline with and without dextrose on the course of labor in nulliparas. Am J Obstet Gynecol. 2009;200(4):379 e1-6. doi: 10.1016/j.ajog.2008.11.030. [PubMed: 19217592].
Sharma C, Kalra J, Bagga R, Kumar P. A randomized controlled trial comparing parenteral normal saline with and without 5% dextrose on the course of labor in nulliparous women. Arch Gynecol Obstet. 2012;286(6):1425-30. doi: 10.1007/s00404-012-2485-1. [PubMed: 22865033].
Smith MD, McCall J, Plank L, Herbison GP, Soop M, Nygren J. Preoperative carbohydrate treatment for enhancing recovery after elective surgery. Cochrane Database Syst Rev. 2014;(8). CD009161. doi: 10.1002/14651858.CD009161.pub2. [PubMed: 25121931].
Fukuda I, Matsuda H, Sugahara S, Kazama T. The effect of intravenous glucose solutions on neonatal blood glucose levels after cesarean delivery. J Anesth. 2013;27(2):180-5. doi: 10.1007/s00540-012-1516-1. [PubMed: 23143044]. [PubMed Central: PMC3622020].
Yatabe T, Tateiwa H, Ikenoue N, Kitamura S, Yamashita K, Yokoyama M. Influence of administration of 1 % glucose solution on neonatal blood glucose concentration in cesarean section. J Anesth. 2013;27(2):302-5. doi: 10.1007/s00540-012-1512-5. [PubMed: 23132181].
Mercier FJ, Augè M, Hoffmann C, Fischer C, Le Gouez A. Maternal hypotension during spinal anesthesia for caesarean delivery. Minerva Anestesiol. 2013;79(1):62-73.
Arora P, Singh RM, Kundra S, Gautam PL. Fluid administration before caesarean delivery: Does type and timing matter? J Clin Diagn Res. 2015;9(6):UC01-4. doi: 10.7860/JCDR/2015/12083.6008. [PubMed: 26266190]. [PubMed Central: PMC4525580].
Faiz SH, Rahimzadeh P, Imani F, Bakhtiari A. Intrathecal injection of magnesium sulfate: shivering prevention during cesarean section: a randomized, double-blinded, controlled study. Korean J Anesthesiol. 2013;65(4):293-8. doi: 10.4097/kjae.2013.65.4.293. [PubMed: 24228140]. [PubMed Central: PMC3822019].
Nette RW, Krepel HP, van den Meiracker AH, Weimar W, Zietse R. Specific effect of the infusion of glucose on blood volume during haemodialysis. Nephrol Dial Transplant. 2002;17(7):1275-80. [PubMed: 12105252].
Gosmanov AR, Smiley DD, Peng L, Siquiera J, Robalino G, Newton C, et al. Vascular effects of intravenous intralipid and dextrose infusions in obese subjects. Metabolism. 2012;61(10):1370-6. doi: 10.1016/j.metabol.2012.03.006. [PubMed: 22483976]. [PubMed Central: PMC3738183].
Wilson D, Douglas J, Heid R, Rurak D. Preoperative dextrose does not affect spinal-induced hypotension in elective Cesarean section. Can J Anaesth. 1999;46(11):1024-9. doi: 10.1007/BF03013196. [PubMed: 10566921].
Brenck F, Hartmann B, Katzer C, Obaid R, Bruggmann D, Benson M, et al. Hypotension after spinal anesthesia for cesarean section: identification of risk factors using an anesthesia information management system. J Clin Monit Comput. 2009;23(2):85-92. doi: 10.1007/s10877-009-9168-x. [PubMed: 19277879].