Comparison of colloid preload versus coload under low dose spinal anesthesia for cesarean delivery.

BACKGROUND: Although fluid bolus is considered as a conventional prophylactic measure to prevent spinal-induced hypotension; vasopressors are nevertheless required. Low dose spinal anesthetics could markedly reduce such episodes of hypotension, by minimizing sympathetic blockade. AIMS: We chose to compare the relative efficacy of colloid preload versus coload under low dose spinal anesthesia, for elective cesarean delivery. SETTINGS AND
DESIGN: A prospective, randomized, double-blinded study.
MATERIALS AND METHODS: In total, 42 parturients were randomized to receive a preload (Group P) of hydroxyl ethyl starch (10 ml/kg) over 20 min before initiation of low dose spinal anesthesia (hyperbaric bupivacaine 5.5 mg with fentanyl 25 μg) or coload (Group C) of an identical fluid over 5 min, starting at the time of identification of cerebrospinal fluid. Our primary outcome included hemodynamic parameters and the incidence of hypotension. The neonatal outcome and side-effects were also monitored. STATISTICAL ANALYSIS: Mann-Whitney U test and Fisher's exact/Chi-square test, whichever appropriate. A P < 0.05 was considered to be significant.
RESULTS: The incidence of hypotension was lower in Group P (10%) when compared with Group C (25%), though insignificant statistically. The hemodynamic parameters were better in Group P, though intergroup statistical differences were not observed. The time to the first episode of hypotension was longer in the Group P (17 min) as compared with Group C (14 min). No notable side-effects or adverse neonatal outcome was noted.
CONCLUSION: Colloid preload has a clinical advantage over the coload strategy, in reducing hypotensive episodes under low dose spinal anesthesia. Preload is better under large hemodynamic fluctuations while coload is preferable for emergency scenarios.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Spinal-induced hypotension (SIH) remains the most common intraoperative anesthetic complication during cesarean delivery. It is considered to be a combined effect of reduced cardiac output and decreased systemic vascular resistance (SVR), secondary to sympathetic blockade during the spinal anesthesia. The relative efficacy of various maneuvers and drugs continues to be contentious, in the prevention of above complication. Though intravenous (IV) fluid boluses and left uterine displacement are considered as a conventional prophylactic measure to augment the venous return (thereby cardiac output), vasopressors are nevertheless required to treat any significant decrease in SVR.[1] Apart from this, low dose spinal anesthesia has also been shown to markedly reduce the incidence of hypotension by causing less intense sympathetic blockade and thus providing a stable SVR.[2]

Data regarding the combined use of colloid bolus and low dose spinal anesthesia in reduction of hypotension during cesarean delivery is scarce in the published literature.[3] With the recent focus is on the timing of fluid bolus (preload or coload) and the viability of colloids, we chose to compare the relative efficacy of colloid preload versus coload in reduction of hypotension during cesarean delivery, under the settings of low dose spinal anesthesia.

MATERIALS AND METHODS

After ethical approval and written-informed consent, 42 parturients, American Society of Anesthesiologists Grade I-II, aged 18-40 years, height 145-165 cm, body mass index 25 ± 10%, >37 weeks of gestation, with a uncomplicated pregnancy, scheduled for elective cesarean delivery, in between June 2012 and December 2012, were included in this trial. Patients having pregnancy-induced hypertension, chronic hypertension, multiple gestation, weight >100 kg, any end organ disease, anemia (hemoglobin concentration <8 g/dl), drug hypersensitivity or any contraindication to regional anesthesia were excluded.

Using computer generated random numbers, parturients were assigned to one of the two groups: Group P to receive a preload of Hydroxyl ethyl starch (6%) @10 ml/kg (IV) over 20 min, before inducing spinal anesthesia or Group C coloaded with the same fluid @10 ml/kg (IV) over 5 min, starting at the initiation of spinal anesthesia. All parturients were given 0.5% hyperbaric bupivacaine 1.1 ml (5.5 mg) with a fixed dose of fentanyl (25 μg) diluted to 2.5 ml volume with normal saline through intrathecal route. A two-operator technique was employed to prevent the observer bias. Randomization was performed by an Anesthetist, intended to deliver the studied fluid and to initiate spinal anesthesia. Further interventions and monitoring were conducted by a second anesthetist blinded to group allocation. To ensure the adequacy of blinding, the reservoir bag and IV tubing of the studied fluid were kept covered with an opaque cloth to shield it from the outcome assessor's view.

After adequate fasting, all patients were premedicated with Metoclopramide (10 mg, IV) and Ranitidine (50 mg, IV), 2 h prior to the procedure. On arrival to the operative room, standard monitors were attached and baseline parameters recorded. At 20 min before the induction of anesthesia, studied fluid was attached to the IV cannula (18 Gauge) and infusion was initiated depending on group allocation. All patients were positioned in a sitting position for combined spinal-epidural technique. Under full aseptic conditions, a 18-Gauge Tuohy needle (Espocan, B. Braun, Germany) was inserted into the L3-4 or L4-5 interspace and epidural space was confirmed using loss of resistance to 2 ml of air. Thereafter, the intrathecal sac was punctured with a 27-Gauge Whitacre spinal needle using a needle-through-needle technique. After confirming free flow of cerebrospinal fluid, considered as initiation of spinal anesthesia, the prepared drug solution was injected. The spinal needle was then withdrawn and epidural catheter was then inserted 4-5 cm in the epidural space and after securing the catheter, the cases were immediately turned supine with a 15° left lateral tilt. Maintenance fluid (Ringer lactate) was replaced with the reservoir bag of studied fluid, 5 min after the initiation of spinal anesthesia and thereafter infused at a rate of 10 ml kg-1 h-1 throughout the intraoperative period. The level of sensory blockade was evaluated bilaterally (defined as sensation to pin prick) in an ascending fashion from T12 dermatome, at 5 min intervals for first 20 min and thereafter at 10 min intervals, until the completion of the procedure. Surgery was allowed to commence, once T5 dermatomal level was achieved. An effective dose was defined as the one that resulted in a sensory block height to T5 level within 20 min of the intrathecal injection with no epidural top-up requirements (maternal abdominal discomfort = 5 on a 10-point numerical score or on maternal request for rescue) within 60 min of spinal anesthesia. All ineffective doses were managed by administering epidural top-ups of 4 ml plain bupivacaine (0.5%) and such cases were excluded from the study.

All patients were continuously monitored for any hemodynamic variations (primary outcome) (heart rate [HR], blood pressure [BP]), recorded at 2 min intervals for the first 20 min and thereafter at 5 min intervals, until the completion of surgery. Any episode of hypotension (systolic BP below 90 mm of Hg or >25% of the baseline) was treated with a bolus dose of phenylephrine (25 μg IV) and additional rapid infusion of lactated Ringer's solution. Vasopressor was repeated every 2 min if hypotension persisted or recurred. Bradycardia (heart rate <50 beats/min) was treated with injection. Atropine 0.5 mg IV bolus. Any episode of nausea or vomiting was treated by a bolus dose of Ondansetron (4 mg, IV). Supplemental oxygen was delivered through a facemask, if SpO2 falls below 94%.

All statistical analyses were performed using the “IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY: IBM Corp”. The continuous variables (demographic characteristics, hemodynamic parameters, fetal blood gas parameters, Apgar score, vasopressor requirement and sensory characteristics) were compared by Mann-Whitney U test. Discrete variables (side-effects) were compared using Fisher's exact test/Chi-square test, whichever appropriate. A P < 0.05 was considered significant.

To detect a 20% difference in the primary outcome among the groups with a standard deviation of 22% estimated from initial pilot observations, with 80% power and 5% alpha error, 20 subjects per group were required. We selected 21 parturients in each group, to compensate for an expected drop out rate of 5%, estimated from initial pilot observations. The sample size was calculated using the power and sample size calculator of the department of biostatics, Vanderbilt University, USA.

RESULTS

Of the 42 cases enrolled for the study, two were excluded from data analysis (1 in each group) due to the requirement of epidural supplements during the intraoperative period. Thus, 20 cases in each group completed the study successfully. The study groups were comparable in terms of the demographic profile, baseline hemodynamics, estimated intraoperative blood loss, IV fluid usage and the duration of surgery [Table 1].

Table 1

Comparison of baseline characteristics

The median height of maximal sensory blockade (T5 dermatome in both groups) and the time required to achieve the same were comparable between the groups [Table 2]. The incidence of hypotension and maximal intraoperative HR were lower in Group P (10%, 100.36 bpm) as compared with Group C (25%, 105.84 bpm), though insignificant statistically. Similarly, the minimum systolic blood pressure, mean arterial pressure (MAP) and diastolic blood pressure (DBP) obtained during intraoperative period were higher in Group P as compared to Group C, however no statistical significance was observed between the groups [Table 2]. The median time to the first episode of hypotension was longer in the Group P (17 min) as compared with Group C (14 min). Phenylephrine requirement was higher in Group C (450 μg) with no significant difference between the groups [Table 2].

Table 2

Comparison of intraoperative characteristics

No notable side-effects were observed in both groups except for an episode of nausea in one patient in Group P versus two patients in Group C. No adverse neonatal outcome was observed in terms of birth weight, Apgar score and acid-base status, in both groups [Table 3].

Table 3

Neonatal outcome

DISCUSSION

Our observation indicates that under low dose spinal anesthesia, colloids attain better hemodynamic stability when administered as a preload bolus in comparison to its coload form, although insignificant statistically underneath the selected sample size for the study. The incidence of hypotension was markedly reduced in both groups (10% in Group P, 25% in Group C) in comparison to previous literature showing an incidence of 68-75% under the conventional spinal anesthetic doses (12.75 mg).[4]

Fluid boluses are aimed at restoration of decreased venous return secondary to sympathetic blockade (decreased SVR), after the initiation of spinal anesthesia.[45] Colloid preload causes a substantial increase in intravascular volume sufficient to offset the effects of increased atrial natriuretic peptide and maintains a constant venous return (consequently cardiac output) in parallel to altered hemodynamics as an effect of spinal anesthesia.[6] Since sympatholysis ensues rapidly after induction of spinal anesthesia, the time to maximal therapeutic effect from a colloid coload may not correspond to the period of evolving hypotension after spinal anesthesia. This phenomenon might have contributed to increased incidence of hypotension in coload group in our study.

Previous study documents incidence of hypotension in 68-75% parturients, who received colloid bolus before or at the initiation of spinal anesthesia (12.75 mg hyperbaric bupivacaine).[4] We observed incidence of 10-25% under the similar methodology, except for low dose spinal anesthesia (5.5 mg). Reduced incidence of hypotension in our study could be attributed to the combined effect of minimally altered SVR under low dose spinal anesthesia and better maintenance of cardiac output by colloid bolus in such circumstances. These findings are also supported by a similar study conducted with colloid preload demonstrating an 18% incidence of hypotension under low dose spinal anesthesia (9 mg).[2] However, our previous study showed a 17.4% incidence of hypotension under the similar spinal anesthetic doses (5.5 mg).[3] Higher incidence of hypotension in that the study could be accredited to use of crystalloid preload or due to higher sympathetic blockade (sensory block: T2-T3 level) as an effect of epidural volume extension. In our study, the time to the first episode of hypotension was 17 and 14 min in preload and coload group, respectively. This period corresponded to the time of fetal delivery, which usually accompanies around 500-800 ml of blood loss and thus requiring vasopressors in some cases. Thus, in other words we effectively prevented any incidence of SIH secondary to sympathetic blockade after initiation of spinal anesthesia.

Previous data shows that varying doses of hyperbaric bupivacaine (3.75-8 mg) have been utilized as a low dose spinal anesthesia.[78910] We chose a dose of 5.5 mg hyperbaric bupivacaine, considering its safety and efficacy in reduction of hypotension and low failure rates (5%) for cesarean delivery under spinal anesthesia.[2] With regard to colloid of choice, we opted for Hydroxyl ethyl starch (6%), considering its wider margin of safety against venous thrombosis and allergic reactions.[11] It is also considered to be safe for the neonate and placental transfer has been found to be negligible even at a 10% concentration in various experimental studies.[12] In addition, its 100% volume retaining effect lasts only for 30 min, which is considered as ideal period to cover the interval between initiation of spinal anesthesia and cesarean delivery.[13] These observations are also supported by its widespread use and efficacy during cesarean delivery in the previous literature.[46]

Hemodynamic alterations were less profound by colloid preload in comparison with coload strategy in our study. Teoh and Sia also demonstrated an advantageous role of colloid preload over coload, in the maintenance of cardiac output after spinal anesthesia.[14] However, they did not recorded MAP or DBP, which are more likely to be related to uteroplacental perfusion. In our study, there were only minor fluctuations in DBP and MAP values, which could have contributed to the relatively stable uteroplacental perfusion and consequently favorable neonatal outcome in all the enrolled cases, with no intergroup differences. There were also no significant maternal side-effects except for an episode of nausea/vomiting in one case in preload groups and two cases in coload group.

Limitations

The lack of the control group prohibited the calculation of an absolute reduction in the incidence of hypotension. We omitted it as withholding fluids shall be against ethical clinical practice. Since the duration of effective sensory-motor blockade is shorter under low dose spinal anesthesia, these doses should not be used for surgeries of longer duration or complicated cesarean deliveries where maintenance of maternal hemodynamics is at most important. Furthermore, larger randomized trials are required for documenting its statistical significance and advocacy in the clinical practice.

CONCLUSION

Colloid preload has a clinically advantage over the coload strategy in reducing hypotensive episodes, under low dose spinal anesthesia for cesarean delivery. Preload should be advocated for situations where large hemodynamic fluctuations are anticipated, although coload is better suited for emergency scenarios, due to shortage of enough time for fluid preloading in such circumstances. Understanding the individual benefit with each strategy allows for better planning of anesthesia and selection of either approach should be based upon the need of the hour against the chances of maternal hypotension.