Prevention of altered hemodynamics after spinal anesthesia: A comparison of volume preloading with tetrastarch, succinylated gelatin and ringer lactate solution for the patients undergoing lower segment caesarean section.

BACKGROUND: Spinal anesthesia has replaced general anesthesia in obstetric practice. Hemodynamic instability is a common, but preventable complication of spinal anesthesia. Preloading the circulation with intravenous fluids is considered a safe and effective method of preventing hypotension following spinal anesthesia. We had conducted a study to compare the hemodynamic stability after volume preloading with either Ringer's lactate (RL) or tetrastarch hydroxyethyl starch (HES) or succinylated gelatin (SG) in the patients undergoing cesarean section under spinal anesthesia.
MATERIALS AND METHODS: It was a prospective, double-blinded and randomized controlled study. Ninety six ASA-I healthy, nonlaboring parturients were randomly divided in 3 groups HES, SG, RL (n = 32 each) and received 10 ml/kg HES 130/0.4; 10 ml/kg SG (4% modified fluid gelatin) and 20 ml/kg RL respectively prior to SA scheduled for cesarean section. Heart rate, blood pressure (BP), oxygen saturation was measured.
RESULTS: The fall in systolic blood pressure (SBP) (<100 mm Hg) noted among 5 (15.63%), 12 (37.5%) and 14 (43.75%) parturients in groups HES, SG, RL respectively. Vasopressor (phenylephrine) was used to treat hypotension when SBP <90 mm Hg. Both the results and APGAR scores were comparable in all the groups. Lower preloading volume and less intra-operative vasopressor requirement was noted in HES group for maintaining BP though it has no clinical significance.
CONCLUSION: RL which is cheap, physiological and widely available crystalloid can preload effectively and maintain hemodynamic stability well in cesarean section and any remnant hypotension can easily be manageable with vasopressor.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Spinal anesthesia for cesarean sections has proved its popularity and has gradually replaced general anesthesia as it overcomes the common problems of general anesthesia such as difficult intubation, increased chance of gastric acid aspiration and fetal hypoxia.[12] In spite of its advantages such as rapid onset of action and better quality of sensory and motor block, hemodynamic instability after spinal anesthesia for cesarean section remain a common and serious complication.[3] To reduce the incidence and severity of hemodynamic instability various techniques such as left lateral tilt, manual uterine displacement[3] uses of vasopressor drugs,[4] preloading or intravascular volume expansion with crystalloid or colloid have been proposed.[5] Preloading with crystalloid and various types of colloids are one of the important measures for prevention of hypotension with spinal anesthesia.[56] An endeavor was made to determine and compare the alteration of hemodynamic status after volume preloading with either tetrastarch (6% hydroxyl ethyl starch [HES 130/0.4]) or succinylated gelatin (SG) or Ringer lactate (RL) solution in patients undergoing cesarean section under spinal anesthesia in prospective double blinded parallel group randomized controlled study.

MATERIALS AND METHODS

This study was performed during the period from June 2011 to January 2012. After obtaining approval from the institutional ethical committee and written informed consent from 96 non-laboring healthy parturients (ASA grade I) age group between 20 and 30 years scheduled for elective cesarean section were randomly allocated by computer derived random number into three equal groups (n = 32) according to preloading fluid they received. Group hydroxyethyl starch (HES) (received 10 ml/kg tetrastarch [HES 130/0.4] or up to a maximum of 500 ml over 20 min), Group SG (received 10 ml/kg SG or up to a maximum of 500 ml over 20 min) and Group RL (received 20 ml/kg RL over 20 min). Infusion started just 20 min prior to spinal anesthesia. Study solution was prepared and wrapped in a black cover by an assistant not contributing in the study and hence that the investigator is blinded to the study solution. The infusion was administered with the help of infusion pump Baxter Flo-Gard 6201™.

Pregnancy with hypertension, diabetes, heart diseases, fetal distress, moderate to severe anemia (<8 gm%), hepatorenal compromise, patient refusal, infection at the site of injection, any known allergy to bupivacaine, bleeding diathesis, elevated intracranial pressure, spine deformity and patients with major systemic illness were excluded from the study.

On arrival at the operation theater, standard multi parameter monitor was attached. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), was recorded as baseline values. After confirming fetal heart sound by an obstetrician, intravenous (IV) access was secured with 18-G cannula in all patients. Under strict aseptic precaution, spinal anesthesia was administered in a sitting position at L3/4 intervertebral space with 26-G Quincke's type spinal needle and 2 ml 0.5% Bupivacaine Heavy along with 0.5 ml Fentanyl (25 μg) were administered at the rate of 0.2 ml/s. The patient was then kept in supine with a 15 cm wedge under the right buttock and oxygen was administered at 2-3 l/min through nasal oxygen cannula. 5 IU oxytocin was given as IV bolus after delivery of baby and 10 IU was given as slow IV infusion in RL which continued throughout surgery and also in the post-operative period.

HR, SBP, DBP and MAP were recorded just after completion of test solution, every 5 min for first 30 min after spinal anesthesia, every 10 min up to end of operation, every 30 min up to 2 h post-operatively. SPO2 and electrocardiogram were monitored continuously in peri- and post-operative period and any adverse effects like nausea-vomiting or any other discomfort was also noted. Any decrease in SBP < 100 mmHg or a drop > 20% of baseline value was considered as hypotension and SBP < 90 mm Hg was treated with bolus IV 80 μg phenylephrine which may be repeated after 5 min if SBP not corrected. Tachycardia was defined as HR > 100 and bradycardia when HR < 60. When HR falls < 50 beats/min injection atropine 0.5 mg IV was administered.

For the purpose of sample size calculation SBP was taken as a primary parameter of interest. It was calculated that 32 subject will be required per group in order to detect a difference of 6 mmHg between two groups with 80% power and 5% probability of type 1 error respectively. This calculation assumed standard deviations of 15 mmHg for SBP giving a root mean square standardized effect value of 0.4 for three groups. Sample size calculation was done by Statistica version 6.

For statistical analysis, the raw data were entered into Microsoft excel spread sheet and analyzed by appropriate statistical software, namely Statistica version 6 and SPSS® statistical package version 17.0 (SPSS Inc., Chicago, IL, USA). Normally distributed numerical variables were compared between the groups by Analysis of Variance followed by Tukey's test as post-hoc test for comparison between two individual groups. Categorical variables were compared between groups by Chi-square test. All analyses were two-tailed and a P < 0.05 was considered to be statistically significant.

RESULTS

Demographic data were comparable in all three groups [Table 1]. These groups had comparable maximal dermatomal distribution and no difference in quality of sensory and motor block. There was statistically no significant difference in age and height and weight.

Table 1

Comparison of demographic data between the three study groups

The pre-operative HR was comparable between three groups. HR remained stable during preloading. All three groups showed a comparable rise in HR at the time of insertion of spinal needle. The groups showed a comparable rise in HR at the time between 15 and 35 min which here coincided with the fall in SBP. This was followed by a decreasing trend in HR until the end of surgery (50 min in most cases). The HR was stable until 240 min [Figure 1 and Table 2]. The HRs in all the groups were quite comparable throughout the study period. A clinically significant fall in HR >20% from the baseline occurred in 2 patients in the group HES, 1 patient in group SG and 5 patients in the group RL. Though the fall was >20% the HR was always greater than 60/min. However one patient in group SG needed injection atropine due to bradycardia.

Figure 1

Mean heart rate among hydroxyethyl starch, succinylated gelatin and Ringer's lactate group

Table 2

Comparing the perioperative mean HR (beats/min) between the three study groups at succeeding time intervals

The mean baseline SBP was comparable between the groups. The same trend was maintained throughout the period of preloading. (P = 0.155). There was rise in SBP in all the groups after 15 min. Incidence of hypotension (SBP < 100 mmHg) was seen in 5 patients of group HES (15.63%), 12 of group SG (37.5%) and 14 of group RL (43.75%) and among them 3,5 and 9 patients require phenylephrine (80 μg at a time) respectively for treatment of hypotension [Table 3].

Table 3

Comparing the perioperative mean SBP (mmHg) between the three study groups at succeeding time intervals

Comparing the peri-operative MAP between the groups under study, there was statistically significant difference between group HES and group RL at 20 min (P = 0.011), 25 min (P = 0.005), 35 min (P = 0.012), 120 min (P = 0.001) and 180 min (P = 0.003) [Figure 2 and Table 4].

Figure 2

Mean arterial pressure among hydroxyethyl starch, succinylated gelatin and Ringer's lactate group

Table 4

Comparing the perioperative mean of MAP (mmHg) between the three study groups at succeeding time intervals

Comparing the peri-operative mean SPO2, APGAR score (1 min and 5 min), intra-operative vasopressor doses used, nausea frequency between the groups under study, among the 96 subjects, nausea was felt by 9 subjects. Among them 2 are from group SG and 6 from group RL. The difference was statistically not significant and only 17 received vasopressor: Group HES –3 (9.38%), group SG — 5 (15.63%), group RL — 9 (28.12%) [Table 5].

Table 5

Comparison of hypotension, vasopressor use, APGAR score between 3 study groups

DISCUSSION

Hypotension during spinal anesthesia for caesarean delivery can have detrimental effects on both mother and neonate; these effects include decreased uteroplacental blood flow, impaired fetal oxygenation with asphyxial stress and fetal acidosis and maternal symptoms of low cardiac output, such as nausea, vomiting, dizziness and decreased consciousness.[7] Therefore, there has been much attention in the literature to methods of preventing and treating hypotension in obstetric anesthesia. Uterine displacement is routine, whereas the use of IV fluid preload is controversial.[8] Despite these conservative measures, a vasopressor drug is often required.

In spite of all controversies prehydration with crystalloid or colloid before spinal anesthesia has widely been used. Because Wollman and Marx[9] proposed the importance of fluid infusion to counteract the relative hypovolemia induced by spinal anesthesia, various fluids, including crystalloids and colloids, have been used for preloading before spinal anesthesia for caesarean section. Many of the studies have been reported[10111213] regarding the effects of volume preload, using various fluids, on the incidence and severity of hypotension induced by spinal anesthesia. Park et al. studied the effects of varying volumes of crystalloid administration and its effects on maternal hemodynamics and colloid osmotic pressure and concluded that the 20 and 30 ml/kg groups showed a larger decline in maternal COP than the 10 ml/kg group; no differences in neonatal COP were seen with varying preload.[10] Mathru et al. concluded that infusion of 5% albumin in D5RL (15 ml/kg) combined with left uterine displacement is an effective means of acute hydration for prevention of hypotension during cesarean sections performed under spinal anesthesia.[11] A study done by Rout et al. demonstrated that rapid (20 ml/kg over either 20 min or 10 min) administration of crystalloid preload before spinal anesthesia did not decrease the incidence or severity of hypotension.[12] Baraka et al. concluded that prophylactic administration of gelatin is more effective than saline in attenuating spinal anesthesia-induced hypotension.[13]

The demographic (age, weight and height) profile; between three groups which was statistically insignificant (P > 0.05); of our patients was quite similar with other research investigations and provided us the uniform platform to evenly compare the results obtained.

In our study, the HR remained relatively unchanged during the period of preloading (15 min) among all the groups. This corresponds with similar findings of Mathru et al.,[11] Riley et al.,[14] Ueyama et al.,[15] Mojica et al.[16] There was a rise in the HR at the time of lumber puncture in all three groups whereas in other studies tachycardia corresponded to the periods of hypotension, which occurred after spinal anesthesia. This occurred between 3 and 10 min of lumber puncture in most patients in several studies Rout et al.,[12] Riley et al.,[14] Siddik et al.[17] Our study corresponds with Marhofer et al.,[18] Shroff et al.[19] and Singh and Saha.[20]

In our study, after the onset of preloading, SBP remained stable in three groups till the end of preloading. This is similar to the findings of Mathru et al.,[11] Rout et al.,[12] Baraka et al.[13] and Ueyama et al.[15] The SBP remained unchanged at the time of lumber puncture unlike the HR. After spinal anesthesia, SBP decreased slightly and reached its nadir between 10 and 15 min after lumber puncture. Thereafter, all three groups showed a slight decreasing trend in SBP which became statistically significant at 20 min (P = 0.015), and 25 min (P = 0.037). The fall of SBP in group HES was lesser than that in group RL. This difference was statistically significant though clinically not significant. After 60 min SBP tended to rise. The rising trend of group RL was just below level of group HES [Figure 3]. This difference was statistically significant at 120 min (P = 0.002) though clinically insignificant as the mean SBP values were always >100 mmHg in three groups. The time of decrease in BP corresponds to studies by other workers like Mathru et al.,[11] Rout et al.,[12] Baraka et al.,[13] Ueyama et al.[15] in whose studies SBP decreased maximally from baseline values at periods ranging 4 min after LP[12] to 10 min after LP.[14] In all these studies hypotension was clinically significant necessitating vasopressor therapy. After this period (10-15 min of LP), the SBP remained stable till the end of surgery. In our study the SBP of 3 subjects of group HES (9.38%), 5 subjects of group SG (15.63%) and 9 subjects of group RL (28.12%) decreased to < 90 mmHg 10 to 15 min after spinal anesthesia and required vasopressor to treat hypotension.

Figure 3

Mean systolic pressure among hydroxyethyl starch, succinylated gelatin and Ringer's lactate group

The success of our preloading volumes in maintaining hemodynamic stability and comparatively less incidence of hypotension may be explained by:

Lower mean body weight of our subjects compared with western subjects thus requiring lower preloading volumes.

Lower dose of bupivacaine used (10 mg of 0.5% bupivacaine) in our study.

Riley et al.[14] used 12 mg 0.75% bupivacaine, morphine 0.2 mg and fentanyl 10μg. French et al.[21] used 2.5-3.0 ml of 0.5% bupivacaine (12.5-15 mg), Siddik et al.[17] used 13 mg 0.75% bupivacaine, Ueyama et al.[15] used 8.0 tetracaine with 0.1 mg morphine in 10% dextrose. In our study, the dose of bupivacaine (0.5%) was 2 ml (10 mg) with fentanyl 25μg used as additives.

Above mentioned researchers managed hypotension with ephedrine use. But Lee et al.[22] in commented in a review article that the use of phenylephrine was associated with better fetal acid-base status and the traditional idea that ephedrine is the preferred choice over phenylephrine for the management of maternal hypotension during spinal anesthesia for elective cesarean delivery in healthy, non-laboring women was not true. Veeser et al.[23] also accepted that phenylephrine is a relatively safe and efficacious peripartum pressor agent that maintains better placental perfusion than ephedrine. Using these experiences we have managed hypotension with phenylephrine.

Marhofer et al. in[18] noted that they did not find significant differences in any initial hemodynamic baseline values between the study groups. MAP decreased significantly following spinal anesthesia in group RL compared with group H (Hetastarch). Our study had also a statistically significant fall in MAP in RL group but it is of mere clinical significance.

APGAR score of our study corresponds with the study of Riley et al.,[14] Siddik et al.,[17] French et al.,[21] Singh and Saha.[20]

Intra-operative vasopressor (phenylephrine) dosing used in our study corresponds with various studies incorporated in systemic review by Lee et al.[22] and kept as 80 μg at a time when SBP < 100 mmHg or a drop > 20% of baseline value.

In comparison of nausea frequency our study corresponds with Riley et al.,[14] Singh and Saha.[20]

In our study, we used 500 ml of HES 130/0.4, 500 ml of SGs and 1000 ml of RL as preloading fluid. This measure has prevented hypotension and maintained hemodynamic stability well. The trends in MAP and DBP were similar to those of SBP. Though the dose of crystalloids used for preloading varies from 10 ml/kg to 30 ml/kg[10] and 20 ml/kg was proven to be safe and effective for both mother and fetus in most studies and is recommended.[128] Patients in Group HES received 500 ml of HES 130/0.4 and in group SG received 500 ml of SG over 15 min prior to spinal anesthesia. Though licensed for up to 50 ml/kg/day, we chose 500 ml dose keeping in mind the physiological changes in the mother during pregnancy which predispose her to circulatory overload and pulmonary edema.[1524] These volumes were sufficient to maintain hemodynamic stability and incidence of hypotension is less in group HES and group SG compared to group RL. There are only four studies until date which have shown similar results. 2 studies were by Wollman and Marx of which one showing following administration of 1000 ml of D5RL, hypotension after subarachnoid block was completely prevented.[9] The third study was by Mathru et al.[11] in which preloading with 15 ml/kg of 5% albumin in D5RL prevented hypotension compared to preloading with D5RL alone. Other studies until date have failed to prevent hypotension, though the incidence of hypotension was decreased except the study was by Singh and Saha,[20] no cases of hypotension after volume preloading.

Zarychanski et al.,[25] evaluated the association of HES use with mortality and acute kidney injury in a systematic review and meta-analysis and finally concluded that HES was associated with a significant increased risk of mortality and acute kidney injury in seriously ill patients. Clinical use of HES for acute volume resuscitation is not warranted due to serious safety concerns. From the above recent studies it seems that harms of HES in some special (like-sepsis) conditions most likely outweigh the benefits and suggest that these products should not be used for acute volume resuscitation of critically ill patients.

CONCLUSION

After compilation and comparing of data it has been found that though statistically HES is better than SG and RL for preloading and hemodynamic maintenance of non-laboring parturients during caesarean section, the result is clinically not so significant and hypotension can easily be managed with available vasopressor like- phenylephrine. Incidence of nausea and APGAR scores were also clinically and statistically insignificant.

Hence we can conclude that RL which is cheap, more physiological and widely available crystalloid which can maintain hemodynamic stability well and free of colloid related hazards is still now a good choice for preloading and maintenance fluid during cesarean section.