A prospective randomized controlled study comparing intrathecal bupivacaine combined with fentanyl and sufentanil in abdominal and lower limb surgeries.

BACKGROUND: Hyperbaric bupivacaine along with either fentanyl or sufentanil as additive, has been widely used in spinal anesthesia. In the present study, we compared the analgesic effects of intrathecal fentanyl versus sufentanil combined with bupivacaine for surgical procedures over the abdomen and lower limbs. SETTINGS AND
DESIGN: This was randomized controlled study conducted in a tertiary care hospital attached to a medical school.
METHODS: Sixty American Society of Anesthesiologists I and II patients were randomized into three groups by sealed envelope technique. Group 1 was to receive bupivacaine with fentanyl; group 2 to receive bupivacaine with sufentanil and group 3 to receive bupivacaine with saline (control), intrathecally. The parameters checked were hemodynamic changes, onset and duration of sensory block, duration of analgesia and maximal sensory level achieved. STATISTICAL ANALYSIS: The data collected were analyzed using χ2 test and paired Student's t-test.
RESULTS: The time taken for the onset of analgesia was longest in the control group followed by fentanyl group. The earliest onset of action of 9.35 ± 1.92 min was recorded in sufentanil group. Duration of sensory blockade and analgesia was longest for fentanyl group than the other groups. Adverse effects noted were more for sufentanil group but were self-limiting.
CONCLUSION: Fentanyl with bupivacaine produced prolonged analgesia and delayed two-segment regression and demonstrated reduced incidence of complications as compared with intrathecal sufentanil. As the quality of analgesia was complete and comparable, fentanyl emerges as a better option for analgesia and it is much economical too when compared to sufentanil.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Painless surgery and painless postoperative period is probably the greatest gift that can be given to the patients. Epidural and intrathecal administration of drugs have been increasingly used for relief of pain. Among the various drugs studied, fentanyl and sufentanil hold good promise and are still being studied for their analgesic efficacy. Fentanyl alone has been assessed for its effect by numerous authors and has been compared with other narcotics intrathecally. There were a few studies describing the effect of fentanyl in prolonging the duration of analgesia after spinal anesthesia. Some studies showed that there was no effect on onset and duration of sensory block with plain bupivacaine or with fentanyl added, but the duration of analgesia was prolonged in fentanyl group.[12] Some articles compared the use of intrathecal fentanyl for caesarean section and it was found that limited dose of intrathecal fentanyl did not cause maternal respiratory depression or changes in neonatal Apgar scores and can effectively prolong the analgesic effect of bupivacaine.[3] Thus the previous studies shows that additives, if combined with hyperbaric bupivacaine can effectively prolong the duration of analgesia while reducing the incidence of adverse effects.

Not many studies have been published on the effects of these drugs on surgical procedures occurring below umbilicus, involving different surgical specialties. In our prospective randomized double blinded study our aim was to compare the effect of combining 0.5% hyperbaric bupivacaine with fentanyl or sufentanil on onset, duration and recovery from analgesia. Its hemodynamic effects and adverse effects.

METHODS

The study was undertaken for a period of 3 years. Institutional Ethics Committee approval was obtained and written informed consent was obtained from the patients. Patients of either sex in the age group of 18–60 years belonging to American Society of Anesthesiologists grade I and II and patients undergoing elective surgery under spinal anaesthesia for any procedure below the level of umbilicus were included. The patients excluded from the study are the persons with body mass index >30 kg/m2, local infection at the site of injection, back pain, patients on chronic analgesic therapy, spine abnormalities, coagulopathies, any known allergies to drugs and pregnancy.

The prospective randomized double blinded study was done in 60 patients. They were divided into three groups by sealed envelope technique which is a computer generated method of randomization. Detailed preoperative evaluation and all necessary basic investigations were done. Nil per oral status was maintained in all the patients. On the day of surgery, the patients were preloaded with 10–15 ml/kg of ringer lactate.

Spinal anesthesia was performed in lateral position at L3-L4 space by an anesthesiologist blinded to the drug injected. The drug syringes were prepared before injection by another anesthesiologist who was not involved in the study. Intraoperative and postoperative assessments were performed by an anesthesiologist blinded to the patient allocation and study drugs. The first group of patients (fentanyl group) received 25 mcg of fentanyl (Fendrop-sun pharma) in combination with 3 ml of 0.5% bupivacaine (Anawin Heavy-Neon) to make a total volume of 3.5 ml. The second group of patients (Sufentanil group) received 5 mcg of sufentanil (Sufentil-Claris Lifesciences) in combination with 3 ml of 0.5% bupivacaine to make a total volume of 3.5 ml. The last group (control group) received 0.5 ml of normal saline in combination with 3 ml of 0.5% bupivacaine to make a total volume of 3.5 ml. The subarachnoid block (SAB) was performed in the lateral position and the scheduled drug was injected intrathecally.

The data collected include the time of onset of action (interval between the injection to the complete loss of sensation to pin prick), level of sensory blockade, duration of sensory blockade (time to two-segment regression), duration of analgesia (time to request for analgesic supplementation) and hemodynamic effects. Systolic blood pressure (BP), diastolic BPs and pulse rate were recorded every 2 min till 10 min and then every 5 min till 30 min and finally at 45 min interval. After surgery, patients were monitored in the recovery room till spinal anesthesia wore off and were then shifted to the ward.

The data collected were analyzed using χ2 test and paired Student's t-test. Tukey's Honestly Significant Difference, which is a single step multiple comparison test, was used to draw the results.

RESULTS

Sex distribution of patients between the groups was not statistically significant (P < 0.33). The fentanyl group had 9, 3 and 8 patients undergoing procedures in general surgery, gynecology and orthopedics respectively. The sufentanil group had 6, 3, 2 and 9 patients for undergoing procedures in general surgery, gynecology, orthopedics and urology, respectively. The control group had 3 and 17 patients for procedures in general surgery and urology. No significant intergroup differences were identified with regard to individual characteristics, duration of surgery and total fluid use.

The change in the heart rate of patients among all the groups has been statistically not significant after the SAB [Graph 1].

Graph 1

Comparison of mean heart rate among the three groups

The fall in the systolic BP from the baseline after SAB in the sufentanil group was significant statistically at 6th and 8th min (P 0.049). However, it did not warrant any treatment with vasopressors [Graph 2]. There was no statistically significant change in diastolic BP between the three groups [Graph 3].

Graph 2

Comparison of systolic blood pressure among the three groups

Graph 3

Comparison of diastolic pressure among the three groups

The time taken for the onset of analgesia recorded in different groups varied and the difference were very highly significant (P < 0.001). It was the longest in the control group, 14.55 ± 2.19 min followed by 13 ± 2.73 min in the fentanyl group. The earliest onset of action at 9.35 ± 1.92 min was recorded in sufentanil group [Graph 4].

Graph 4

Comparison of onset of sensory blockade

The maximum level of T4 was achieved in 13 patients in fentanyl group while 11 patients in sufentanil group achieved this level. Only 3 patients in control group achieved T4 level (P < 0.002) [Graph 5].

Graph 5

Comparison of highest sensory level

Duration of sensory blockade assessed by two-segment regression took 82.45 ± 15.58 min in the control group, 122.55 ± 12.56 min in sufentanil group and the longest of 152 ± 10.93 min with fentanyl group. The intergroup comparison indicates that it is very highly significant (P < 0.001) [Graph 6].

Graph 6

Comparison of mean two-segment regression

The patients in the control group requested at 119 ± 14.65 min for supplemental analgesics, fentanyl group requested at 216.70 ± 27.48 min, whereas sufentanil group requested at 160.55 ± 27.01 min. The analgesia produced by fentanyl intrathecally has been the longest, up to 3½ h and almost 1 h more than sufentanil. The intergroup variation is very highly significant (P < 0.001) [Graph 7].

Graph 7

Comparison of mean request time

Nineteen patients from the fentanyl group, 7 patients from the sufentanil group and 13 from the control group did not have any of the known complications of narcotics or spinal anesthesia. One patient in fentanyl group and 6 patients in sufentanil group had hypotension. The adverse effects noted were given in Table 1.

Table 1

Complications in each group. Fentafentanyl group, sufenta-sufentanil group

DISCUSSION

Moderate to severe pain affects roughly half of all postsurgical patients upholding the urgent need for reassessment of the conventional approach to pain therapy. The approach to total pain relief is multimodal analgesia using a combination of drugs or techniques. The major advantage of the “selective” blockade of pain by spinal opioids is that, the absence of sympathetic blockade and postural hypotension, potentially allowing early ambulation of patients. However, early and late respiratory depression is a major concern with spinal opioids. An overdose of intrathecal or intravenous opioid may result in sudden apnea necessitating emergent treatment. Usually, the onset of respiratory arrest is gradual with more time available for diagnosis and implementation of the treatment.

Various agents have been used epidurally or intrathecally along with local anesthetic to prolong the analgesia. Of these, fentanyl and sufentanil hold promise and are being evaluated for the risks and the benefits.

The onset and duration of analgesia recorded with fentanyl and sufentanil in the present study were comparable with similar studies conducted earlier.

Hemodynamic parameters

In the present study, we found that there were no significant hemodynamic changes between fentanyl group and sufentanil group. In a study comparing intrathecal fentanyl and sufentanil as adjuvants to hyperbaric bupivacaine in lower limb procedures, it was found that there was no significant variation in hemodynamic parameters.[4] In a study conducted by Kim et al., it was found that there was no statistically significant difference in hemodynamic parameters in the fentanyl, sufentanil or control group.[5] Hassani et al. studied comparing 0.5% isobaric bupivacaine 15 mg with 25 mcg fentanyl, 2.5 mcg sufentanil and saline in 90 patients Hemodynamic stability was more with sufentanil compared with fentanyl. The reason may be due to a lower dose of sufentanil (2.5 μg) used when compared to our dose (5 μg).[7]

Respiratory parameters

There were no statistically significant differences in respiratory parameters.[4]

Maximal block height

The maximal block height achieved was T4 in our study while it was T6 in another study. The level was comparable in all the groups.[4] In another study, it was found that peak level of sensory blockade was higher in sufentanil group (T11) than fentanyl group (L1) but this level achieved was significantly lower than our group.[5] In a study conducted by Hassani et al. it was found that maximal block height achieved was T4. 30% of patients in sufentanil group reached this level while only 5% in fentanyl group reached this level.[7] It was comparable to our findings. In another study comparing intrathecal fentanyl and sufentanil for endoscopic urological procedures, it was found that the maximal block height achieved by sufentanil group was (T10-T11) while fentanyl group was (T8-T11), which was significantly lower level achieved than our findings. The difference may be due to the lower dosage of hyperbaric bupivacaine (5 mg) used.[8]

Lee et al. did another study in 72 healthy parturients comparing intrathecal bupivacaine with fentanyl, sufentanil and control group and found that the maximal level of sensory blockade achieved was T3 for all the group.[9]

Sensory block

In our study, the duration of analgesia and of sensory blockade were prolonged with fentanyl group. The onset of sensory blockade was faster with sufentanil group as compared with fentanyl group. In another study comparing intrathecal fentanyl and sufentanil for lower limb surgeries it was found that, the onset of analgesia was faster with sufentanil group (4 ± 1.5 min) compared with fentanyl group (4.73 ± 1.77 min) which was similar to our findings. But the duration of sensory blockade and the duration of analgesia was more with sufentanil group, which was against our findings.[4] Kim et al. found that there was no statistically significant difference in the onset of block level between the two groups and also there was no differences between the three groups on time to two-segment regression.[5] As against our findings, Palmer et al. found that a slower onset of block was noticed in parturients who had received intrathecal sufentanil compared with fentanyl in spite of higher doses of sufentanil used.[6] In our study sufentanil group had a faster onset of action than fentanyl group. The authors cannot ascertain whether the effects of specific gravity of sufentanil with bupivacaine had any role in the faster onset of analgesia. The two-segment regression with fentanyl took at least 30 min longer than with sufentanil group. Complete analgesia also lasted longer with fentanyl, by about 56 min as compared to sufentanil group. In another study it was found that the duration of analgesia was longer with sufentanil group, in spite of using lower dose of sufentanil, which was contradicting our findings. The pain scores were significantly lower with sufentanil group.[7] The onset of sensory block was delayed in fentanyl and sufentanil group as compared to control group in another study. The difference may be due to the lower dose of bupivacaine used in fentanyl, sufentanil group (5 mg) as against control group (7 mg).[8] The duration of block was shorter in control group which was similar to our findings. Quality of analgesia was better and prolonged with sufentanil group whereas in our study analgesia was prolonged with fentanyl group. In a study done by Jung et al., the duration of analgesia was significantly prolonged in fentanyl and sufentanil group when compared with control, fentanyl being slightly more than sufentanil group.[9]

Similar studies conducted with intrathecal bupivacaine and its combination with fentanyl and sufentanil proved that these additives are effective in prolonging the duration of analgesia. In equipotent doses fentanyl and sufentanil provided similar onset and duration of sensory and motor blockade.[1011]

Use of opioids along with bupivacaine has definitely prolonged the duration of analgesia and also helps in early ambulation. Kararmazetal., demonstrated that motor blockade is prolonged with plain bupivacaine than low dose bupivacaine with additives added.[12]

A limitation of our study was we didn’t use equipotent doses of fentanyl and sufentanil. These ‘beneficial’ results with fentanyl group could be partially explained by the argument that the fentanyl group was relatively ‘overdosed’ compared with sufentanil group. There is indirect evidence to suggest that the ratio used in the present study (fentanyl: sufentanil) was higher than the potency ratio of 3.2:1 (fentanyl:sufentanil) for ED50 values (without the addition of any local anaesthetics).[13]

In this context, one must take into consideration the high cost of sufentanil and greater risk of dosing error due to higher potency of sufentanil compared with fentanyl.

Finally when the complications were considered, 95% of the patients from fentanyl group and 55% from sufentanil group did not have any complications. Though sufentanil group had comparatively more complications, they were either self-limiting like pruritus or clinically insignificant hypotension. Thus, quality of analgesia of fentanyl was comparable with that of sufentanil with lesser side-effects.

CONCLUSION

Sufentanil mixed with bupivacaine provided a faster onset of analgesia. Fentanyl group had higher levels of sensory block. Fentanyl with bupivacaine produced prolonged analgesia. To conclude we opine that bupivacaine combined with additives demonstrated reduced incidence of complications, and offer hemodynamic stability. As the quality of analgesia was complete and comparable, fentanyl emerges as a better option for analgesia as it is more economical than sufentanil.