A Randomized Controlled Comparison Between Combined Spinal-Epidural and Single-Shot Spinal Techniques in Morbidly Obese Parturients Undergoing Cesarean Delivery: Time for Initiation of Anesthesia Vernon H. Ross, MD, Laura S. Dean, MD, John A. Thomas, MD, Lynne C. Harris, BSN, and Peter H. Pan, MSEE, MD BACKGROUND: There is no current consensus on the optimal technique for subarachnoid anesthesia in morbidly obese parturients even though some providers prefer the combined spinalepidural (CSE) over single-shot spinal (SSS) technique. In this randomized controlled study, we compared the time required for initiation of subarachnoid anesthesia between SSS and CSE techniques in morbidly obese parturients undergoing elective cesarean delivery. METHODS: Morbidly obese parturients presenting for elective cesarean delivery were randomized to receive subarachnoid anesthesia performed either with a SSS or a CSE technique. The spinal procedure in the sitting position was attempted by an experienced resident for up to 10 minutes, and if unsuccessful, the attending obstetric anesthesiologist assumed control of the procedure. The primary outcome was the time it took from the insertion of the introducer needle (SSS group) or insertion of the epidural needle (CSE group) to the end of intrathecal injection of drugs (procedure time). RESULTS: Forty-four patients were enrolled and completed the study. Three were excluded due to protocol violations. Of the remaining, 21 patients were in the SSS group and 20 in the CSE group. Demographic variables and mean (SD) body mass index (48.7 ± 7.6 kg/m2 for SSS; 49.9 ± 8.6 kg/m2 for CSE) were not different between groups. The median [interquartile range] for procedure time was 210 [116–692] seconds and 180 [75–450] seconds for SSS and CSE groups, respectively (P = 0.36), while the 95% confidence interval (CI) of the difference was −80 to +180 seconds. The first operator completed the procedure in 100 kg presenting for elective CD. Patients were approached for the study when manpower and schedule allowed. Exclusion criteria included any contraindication to neuraxial anesthesia and associated spinal drugs. A computer-generated randomization sequence and allocation (generated with Microsoft Office Excel’s random number function [RAND] and group sorting function) were created for the 2 groups. The randomized group allocation for each subject, listed sequentially on the pages inside a binder securely stored in the research file cabinet for this study, was obtained by the attending anesthesiologist shortly before performing subarachnoid anesthesia for the respective subject. The subjects were randomized to receive subarachnoid anesthesia performed either with a standard SSS technique (SSS group) or a CSE technique (CSE group). The person recruiting the subject was unaware of the subject’s group assignment. The subarachnoid procedure was performed with the patient in the sitting position by an experienced resident or fellow as the first operator. The trainees had performed an average of >100 SSS and 100 epidural or CSE procedures during previously completed obstetric and regional anesthesia rotations. The first operator was allowed up to 10 minutes to complete the procedure (defined as time from the insertion of the introducer for the spinal needle in the SSS group or from insertion of the epidural needle in the CSE group to the injection of intrathecal drugs), and if unsuccessful, the attending obstetric anesthesiologist assumed control of the procedure. In the SSS group, a 25-gauge, 90-mm Whitacre spinal needle (BD Medical, Franklin Lakes, NJ) was inserted through a 20-gauge, 37-mm introducer needle. Operators in the SSS group had the option to begin with or switch to the longer 101-mm, 24-gauge Gertie Marx spinal needle (IMD Inc, Huntsville, UT) or a 25-gauge, 119-mm Whitacre needle at their discretion. In the CSE group, a 17-gauge, 89-mm Weiss epidural needle was used to identify the epidural space, and spinal drug was administered through a 27-gauge, 119mm Whitacre spinal needle using a needle-through-needle technique. Operators in the CSE group also had the option to begin with or change to a longer 127-mm Tuohy epidural needle with a 160-mm, 25-gauge Gertie Marx spinal needle at their discretion. In both groups, free cerebrospinal fluid return in the hub of the spinal needle and free aspirate of cerebrospinal fluid were confirmed before injection of a subarachnoid dose of 1.6 mL hyperbaric bupivacaine (0.75%) with fentanyl 20 µg and preservative-free morphine 200 µg. In the CSE group, the epidural catheter was inserted and secured in the usual manner after removal of the spinal needle. Testing or dosing through the epidural catheter was withheld unless supplement surgical anesthesia was needed. After administration January 2014 • Volume 118 • Number 1
of the subarachnoid dose, patients in both groups were positioned supine with left lateral tilt. Research personnel, not involved with the medical care of the subject, recorded the time for placement of the subarachnoid anesthesia from start of procedure, insertion of each needle to time of intrathecal injection of spinal drugs and successful surgical anesthesia (defined as achieving a sensory blockade to T4 level to cold temperature checked with alcohol every 1 minute until achieving T4 level), as well as the number of attempts for the procedure. An attempt was defined as a change of interspinous space for needle insertion, withdrawing the spinal or epidural needle more than half its inserted length to redirect it, or a change of provider. Patients were asked immediately after successful completion of the neuraxial procedure to report a verbal numeric pain score (0–10, 0 being no pain at all, and 10 being worst pain imaginable) associated with the pain intensity of the neuraxial anesthetic procedure. The primary outcome measure was the time it took from the insertion of the introducer for the spinal needle in the SSS group or the insertion of the epidural needle in the CSE group to successful intrathecal injection of spinal drugs, regardless of which operator successfully completed the procedure. The main secondary outcomes were the proportion of first operators to complete the procedure within 10 minutes and total number of attempts. Other exploratory outcomes were the time it took from intrathecal injection to achieving sensory blockade to T4 level and the patients’ verbal numeric procedure pain scores.
Statistics
Statistical analyses were conducted using SigmaStat version 3.0 for Windows (SPSS Inc., Chicago, IL and then acquired by IBM in 2009). A priori sample size analysis with 2-tailed student t test for power of 0.8 and an α of 0.05 was applied. To detect a clinically relevant time difference of 210 seconds in the primary outcome between groups with a 230-second SD (data based on previous quality assurance medical record review), a priori sample size analysis revealed that a minimum sample size of 20 per group was required. A post hoc noninferiority analysis with the predefined 210 seconds noninferiority margin was also planned. Descriptive statistics were calculated for all variables and compared between groups, such that mean ± SD was used for normally distributed variables; median [interquartile range] for data that were not normally distributed or for data with outliers or ordinal data; and number (percentage) for categorical data. Kolmogorov-Smirnov (with Lilliefors correction) test was used to test for normality of data distribution for each variable. Unpaired 2-tailed t tests were used for comparing parametric data between groups and Mann-Whitney rank sum test for nonparametric data. χ2 analysis and Fisher exact test were applied as appropriate for comparing proportions between groups. Difference between groups and the 95% confidence interval (CI) of the difference were calculated. For data reported in medians, the difference between groups and the 95% CI of the difference were calculated based on Hodges-Lehmann method. For all analyses, P was set at 0.05 for statistical significance. In the Hodges-Lehmann method, the difference between every possible pair of data (x’s and y’s where x and y were data points of the 2 groups, respectively) between the 2 groups
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Combined Spinal-Epidural Versus Single-Shot Spinal for Morbidly Obese Parturients
were calculated to give a total of m times n such differences (where m and n were the sample size of the 2 groups, respectively). The median of this list of m times n differences was determined as the median difference between groups. Then the rank and its associated value for the lower and upper 95% confidence limit were determined in this list of m times n differences, using the standard formula RL = mn/2 − Z α/2 * SQRT[(mn(m + n + 1)/12)], and RU = mn − RL + 1, where Z α/2 was chosen for the 95% confidence level, and RL and RU were the rank number for lower and upper confidence limit of the difference. Although the Hodges-Lehmann method is generally robust for measuring effect size, the analysis may underestimate the positive difference between the CSE and SSS techniques if the data are nonnormally distributed (e.g., significant skew, kurtosis, or outliers).
RESULTS
Forty-four patients were enrolled and completed the study. Three subjects were excluded due to protocol violation (Fig. 1). Of the remaining, 21 patients were in the SSS group and 20 in the CSE group. Demographic variables and BMI were not different between groups (Table 1). The median [interquartile range] time from insertion of introducer to intrathecal injection of drugs was 210 [116– 692] seconds and 180 [75–450] seconds for the SSS and CSE groups, respectively (P = 0.36 with Mann-Whitney rank sum test), while the 95% CI of the difference was −80 to +180 seconds, favoring the CSE group. For the proportion of procedures completed within 10 minutes by the first operator, the 95% CI of the difference between groups was 2% to 45%, favoring the CSE group. For the exploratory measure on the
Figure 1. Subject enrollment, inclusions, and exclusions flow chart.
Table 1. Demographics of the Single-Shot Spinal and Combined Spinal-Epidural Groups Demographic Age (y) Estimated Gestation Age (wk) Parity Height (cm) Weight (kg) BMI (kg/m2) BMI [interquartile range](kg/m2) BMI minimum to maximum (kg/m2) Iliac crest felt to be palpable by first provider (%) Lumbar spinous processes felt to be palpable by first provider (%)
Single-shot spinal (SSS) group (N = 21) 30 ± 6 38 ± 2 1 [1–2] 165 ± 8 134 ± 17 48.7 ± 7.6 [43.5–48.0] 39.3–70.5 62% 38%
Combined spinal-epidural (CSE) group (N = 20) 30 ± 5 38 ± 1 2 [1–2] 167 ± 4 139 ± 25 49.9 ± 8.6 [44.1–55.1] 35.5–64.0 65% 40%
No statistical differences in all demographic variables between groups. Data are presented as mean ± SD except for parity as median [interquartile range], and when otherwise specified as percent. BMI = body mass index.
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Table 2. Comparison of Primary and Secondary Outcomes in All Subjects Between Single-Shot Spinal and Combined Spinal-Epidural Techniques Outcome variables measured Time from start of insertion of spinal introducer (or epidural needle) to intrathecal drug injection (s) Time from subcutaneous lidocaine injection to intrathecal drug injection (s) Time from intrathecal drug injection to established blockade of cold to T4 (s) Percent of subjects with procedures completed within 10 min by first operator (%) Total number of attempts Patients’ self-rating pain score of having the procedure performed on them (0–10)
Single-shot spinal (SSS) group N = 21 210 [116–692]
Combined spinal epidural (CSE) group N = 20 180 [75–450]
P 0.36
Difference between groups and 42
285 [170–740]
257 [120–480]
0.32
15
294 ± 153
347 ± 164
0.29
−53
71
95
0.09
−24
5 [4–10] 4.1 ± 2.5
3 [1–4] 5.1 ± 2.9
0.007 0.24
3 1.0
Data are presented as mean ± SD, median [interquartile range], or percent; and the difference between groups and . Hodges-Lehmann method was used for calculation of the difference between groups and when the data are presented in medians. Data from single shot spinal group was the minuend and combined spinal epidural group the subtrahend in the calculation for the difference and 95% confidence interval of the difference between groups. With the current analysis using Hodges-Lehmann method, the results may underestimate the positive upside difference of using combined spinal epidural versus single shot spinal techniques.
number of attempts to successful completion of the procedure, the 95% CI of the difference between groups was 1 to 6 attempts, favoring the CSE group (Table 2). There was no difference between groups in the time to reach T4 block to cold. No patient in the CSE group had a recognized unintentional dural puncture with the Tuohy needle, and no patient in either group experienced a spinal headache. None of the epidural catheters in the CSE group was needed for surgical anesthesia. Neonatal outcomes (1- and 5-minute Apgar scores) and maternal side effects (excessive high spinal blocks and vasopressor use) were not different between groups (data not shown).
DISCUSSION
Our findings suggest that the CSE technique is noninferior to SSS technique for placement of subarachnoid anesthesia in morbidly obese parturients. Our data showed a statistically insignificant difference of 30 seconds in median times for the primary outcome between groups. We designed our study to detect a 210-second difference for clinical significance because we considered 180 seconds to be the typically recommended time needed for oxygen administration before induction of general anesthesia, plus the 30 seconds we presumed it would take to reposition the patient from an unsuccessful neuraxial anesthetic attempt for general anesthesia. Due to the larger than expected SD, the smaller than expected differences between groups, and the nonparametric distribution of the primary outcome, there was insufficient evidence to reject the null hypothesis with the priori sample size. With the post hoc analysis for noninferiority with the predefined noninferiority margin of 210 seconds, the 95% CI of the primary outcome in the CSE group indicated that CSE was noninferior to the SSS technique and did not require more time than a SSS for subarachnoid anesthesia placement. With our findings of the large variance and small difference in the primary outcome, a post hoc sample size analysis revealed a huge sample size of >1000 would be required to detect such a small true difference of 30 seconds between groups, making such a study impractical. However, our current findings have relevant clinical implications for decision making and also provide important
January 2014 • Volume 118 • Number 1
information for hypothesis generation and a guide for better clinically relevant choices of primary outcomes for future study design on the subject, such as comparing number of attempts to success or success rate with first provider between different neuraxial anesthetic techniques. The exploratory secondary measure suggested a higher likelihood of successful completion of the procedure within 10 minutes with fewer attempts by an experienced resident or fellow with a CSE than with a SSS technique. Though the difference in the success rate did not reach statistical significance (P = 0.09), it may be considered clinically relevant and applicable. Furthermore, future study designs may be more appropriately focused on comparing success rate within 10 or less minutes and number of attempts between these 2 anesthetic techniques than measuring time differences. The literature comparing the success and speed of placement between the CSE and the SSS techniques for morbidly obese patients consists primarily of observational studies or retrospective reviews.10 To our knowledge, no randomized controlled study compared these 2 techniques in morbidly obese parturients. Twenty years ago in a retrospective review of morbidly obese parturients, Hood and Dewan3 suggested epidural anesthesia was more commonly (71%) used for CD. In 2010, Butwick et al.10 reported in a retrospective study that parturients with a BMI ≥40 kg/m2 who underwent elective CD were more likely (60%) to have received CSE for their anesthetic, while the SSS technique was more common (83%) among those with a BMI
of the subarachnoid dose, patients in both groups were positioned supine with left lateral tilt. Research personnel, not involved with the medical care of the subject, recorded the time for placement of the subarachnoid anesthesia from start of procedure, insertion of each needle to time of intrathecal injection of spinal drugs and successful surgical anesthesia (defined as achieving a sensory blockade to T4 level to cold temperature checked with alcohol every 1 minute until achieving T4 level), as well as the number of attempts for the procedure. An attempt was defined as a change of interspinous space for needle insertion, withdrawing the spinal or epidural needle more than half its inserted length to redirect it, or a change of provider. Patients were asked immediately after successful completion of the neuraxial procedure to report a verbal numeric pain score (0–10, 0 being no pain at all, and 10 being worst pain imaginable) associated with the pain intensity of the neuraxial anesthetic procedure. The primary outcome measure was the time it took from the insertion of the introducer for the spinal needle in the SSS group or the insertion of the epidural needle in the CSE group to successful intrathecal injection of spinal drugs, regardless of which operator successfully completed the procedure. The main secondary outcomes were the proportion of first operators to complete the procedure within 10 minutes and total number of attempts. Other exploratory outcomes were the time it took from intrathecal injection to achieving sensory blockade to T4 level and the patients’ verbal numeric procedure pain scores.
Statistics
Statistical analyses were conducted using SigmaStat version 3.0 for Windows (SPSS Inc., Chicago, IL and then acquired by IBM in 2009). A priori sample size analysis with 2-tailed student t test for power of 0.8 and an α of 0.05 was applied. To detect a clinically relevant time difference of 210 seconds in the primary outcome between groups with a 230-second SD (data based on previous quality assurance medical record review), a priori sample size analysis revealed that a minimum sample size of 20 per group was required. A post hoc noninferiority analysis with the predefined 210 seconds noninferiority margin was also planned. Descriptive statistics were calculated for all variables and compared between groups, such that mean ± SD was used for normally distributed variables; median [interquartile range] for data that were not normally distributed or for data with outliers or ordinal data; and number (percentage) for categorical data. Kolmogorov-Smirnov (with Lilliefors correction) test was used to test for normality of data distribution for each variable. Unpaired 2-tailed t tests were used for comparing parametric data between groups and Mann-Whitney rank sum test for nonparametric data. χ2 analysis and Fisher exact test were applied as appropriate for comparing proportions between groups. Difference between groups and the 95% confidence interval (CI) of the difference were calculated. For data reported in medians, the difference between groups and the 95% CI of the difference were calculated based on Hodges-Lehmann method. For all analyses, P was set at 0.05 for statistical significance. In the Hodges-Lehmann method, the difference between every possible pair of data (x’s and y’s where x and y were data points of the 2 groups, respectively) between the 2 groups
www.anesthesia-analgesia.org
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Combined Spinal-Epidural Versus Single-Shot Spinal for Morbidly Obese Parturients
were calculated to give a total of m times n such differences (where m and n were the sample size of the 2 groups, respectively). The median of this list of m times n differences was determined as the median difference between groups. Then the rank and its associated value for the lower and upper 95% confidence limit were determined in this list of m times n differences, using the standard formula RL = mn/2 − Z α/2 * SQRT[(mn(m + n + 1)/12)], and RU = mn − RL + 1, where Z α/2 was chosen for the 95% confidence level, and RL and RU were the rank number for lower and upper confidence limit of the difference. Although the Hodges-Lehmann method is generally robust for measuring effect size, the analysis may underestimate the positive difference between the CSE and SSS techniques if the data are nonnormally distributed (e.g., significant skew, kurtosis, or outliers).
RESULTS
Forty-four patients were enrolled and completed the study. Three subjects were excluded due to protocol violation (Fig. 1). Of the remaining, 21 patients were in the SSS group and 20 in the CSE group. Demographic variables and BMI were not different between groups (Table 1). The median [interquartile range] time from insertion of introducer to intrathecal injection of drugs was 210 [116– 692] seconds and 180 [75–450] seconds for the SSS and CSE groups, respectively (P = 0.36 with Mann-Whitney rank sum test), while the 95% CI of the difference was −80 to +180 seconds, favoring the CSE group. For the proportion of procedures completed within 10 minutes by the first operator, the 95% CI of the difference between groups was 2% to 45%, favoring the CSE group. For the exploratory measure on the
Figure 1. Subject enrollment, inclusions, and exclusions flow chart.
Table 1. Demographics of the Single-Shot Spinal and Combined Spinal-Epidural Groups Demographic Age (y) Estimated Gestation Age (wk) Parity Height (cm) Weight (kg) BMI (kg/m2) BMI [interquartile range](kg/m2) BMI minimum to maximum (kg/m2) Iliac crest felt to be palpable by first provider (%) Lumbar spinous processes felt to be palpable by first provider (%)
Single-shot spinal (SSS) group (N = 21) 30 ± 6 38 ± 2 1 [1–2] 165 ± 8 134 ± 17 48.7 ± 7.6 [43.5–48.0] 39.3–70.5 62% 38%
Combined spinal-epidural (CSE) group (N = 20) 30 ± 5 38 ± 1 2 [1–2] 167 ± 4 139 ± 25 49.9 ± 8.6 [44.1–55.1] 35.5–64.0 65% 40%
No statistical differences in all demographic variables between groups. Data are presented as mean ± SD except for parity as median [interquartile range], and when otherwise specified as percent. BMI = body mass index.
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Table 2. Comparison of Primary and Secondary Outcomes in All Subjects Between Single-Shot Spinal and Combined Spinal-Epidural Techniques Outcome variables measured Time from start of insertion of spinal introducer (or epidural needle) to intrathecal drug injection (s) Time from subcutaneous lidocaine injection to intrathecal drug injection (s) Time from intrathecal drug injection to established blockade of cold to T4 (s) Percent of subjects with procedures completed within 10 min by first operator (%) Total number of attempts Patients’ self-rating pain score of having the procedure performed on them (0–10)
Single-shot spinal (SSS) group N = 21 210 [116–692]
Combined spinal epidural (CSE) group N = 20 180 [75–450]
P 0.36
Difference between groups and 42
285 [170–740]
257 [120–480]
0.32
15
294 ± 153
347 ± 164
0.29
−53
71
95
0.09
−24
5 [4–10] 4.1 ± 2.5
3 [1–4] 5.1 ± 2.9
0.007 0.24
3 1.0
Data are presented as mean ± SD, median [interquartile range], or percent; and the difference between groups and . Hodges-Lehmann method was used for calculation of the difference between groups and when the data are presented in medians. Data from single shot spinal group was the minuend and combined spinal epidural group the subtrahend in the calculation for the difference and 95% confidence interval of the difference between groups. With the current analysis using Hodges-Lehmann method, the results may underestimate the positive upside difference of using combined spinal epidural versus single shot spinal techniques.
number of attempts to successful completion of the procedure, the 95% CI of the difference between groups was 1 to 6 attempts, favoring the CSE group (Table 2). There was no difference between groups in the time to reach T4 block to cold. No patient in the CSE group had a recognized unintentional dural puncture with the Tuohy needle, and no patient in either group experienced a spinal headache. None of the epidural catheters in the CSE group was needed for surgical anesthesia. Neonatal outcomes (1- and 5-minute Apgar scores) and maternal side effects (excessive high spinal blocks and vasopressor use) were not different between groups (data not shown).
DISCUSSION
Our findings suggest that the CSE technique is noninferior to SSS technique for placement of subarachnoid anesthesia in morbidly obese parturients. Our data showed a statistically insignificant difference of 30 seconds in median times for the primary outcome between groups. We designed our study to detect a 210-second difference for clinical significance because we considered 180 seconds to be the typically recommended time needed for oxygen administration before induction of general anesthesia, plus the 30 seconds we presumed it would take to reposition the patient from an unsuccessful neuraxial anesthetic attempt for general anesthesia. Due to the larger than expected SD, the smaller than expected differences between groups, and the nonparametric distribution of the primary outcome, there was insufficient evidence to reject the null hypothesis with the priori sample size. With the post hoc analysis for noninferiority with the predefined noninferiority margin of 210 seconds, the 95% CI of the primary outcome in the CSE group indicated that CSE was noninferior to the SSS technique and did not require more time than a SSS for subarachnoid anesthesia placement. With our findings of the large variance and small difference in the primary outcome, a post hoc sample size analysis revealed a huge sample size of >1000 would be required to detect such a small true difference of 30 seconds between groups, making such a study impractical. However, our current findings have relevant clinical implications for decision making and also provide important
January 2014 • Volume 118 • Number 1
information for hypothesis generation and a guide for better clinically relevant choices of primary outcomes for future study design on the subject, such as comparing number of attempts to success or success rate with first provider between different neuraxial anesthetic techniques. The exploratory secondary measure suggested a higher likelihood of successful completion of the procedure within 10 minutes with fewer attempts by an experienced resident or fellow with a CSE than with a SSS technique. Though the difference in the success rate did not reach statistical significance (P = 0.09), it may be considered clinically relevant and applicable. Furthermore, future study designs may be more appropriately focused on comparing success rate within 10 or less minutes and number of attempts between these 2 anesthetic techniques than measuring time differences. The literature comparing the success and speed of placement between the CSE and the SSS techniques for morbidly obese patients consists primarily of observational studies or retrospective reviews.10 To our knowledge, no randomized controlled study compared these 2 techniques in morbidly obese parturients. Twenty years ago in a retrospective review of morbidly obese parturients, Hood and Dewan3 suggested epidural anesthesia was more commonly (71%) used for CD. In 2010, Butwick et al.10 reported in a retrospective study that parturients with a BMI ≥40 kg/m2 who underwent elective CD were more likely (60%) to have received CSE for their anesthetic, while the SSS technique was more common (83%) among those with a BMI
