Spinal sufentanil associated to hyperbaric bupivacaine: Is it possible to decrease opioid dose?

Abstracts

JUSTIFICATIVA E OBJETIVOS: A adição de bupivacaína isobárica a doses menores de sufentanil por via subaracnóidea promove analgesia de qualidade satisfatória, com menor incidência de efeitos colaterais. O objetivo do estudo foi avaliar a qualidade da analgesia e a incidência de efeitos colaterais de doses reduzidas de sufentanil subaracnóideo associados à bupivacaína hiperbárica em analgesia de parto. MÉTODO: Foram estudadas prospectivamente 69 gestantes de termo em trabalho de parto. As gestantes foram aleatoriamente divididas em três grupos que receberam, no espaço subaracnóideo, a combinação de 2,5 mg de bupivacaína hiperbárica e 1 ml de solução fisiológica (Grupo Controle); 2,5 mg de bupivacaína hiperbárica e 2,5 µg de sufentanil (Grupo S2,5) ou 2,5 mg de bupivacaína hiperbárica e 5 µg de sufentanil (Grupo S5). A dor, de acordo com a escala analógico visual (EAV) de dor e a incidência de efeitos colaterais foram avaliadas a cada 5 minutos nos primeiros quinze minutos e a seguir a cada 15 minutos até o nascimento. O estudo terminava com o nascimento, ou quando a paciente solicitava medicação analgésica de resgate (EAV > 3 cm). RESULTADOS: Os grupos S2,5 e S5 apresentaram maior duração de analgesia (67,2 ± 38,6 e 78,9 ± 38,7 minutos, respectivamente) e maior porcentagem de pacientes com analgesia efetiva (100% e 95,6%, respectivamente) que o grupo Controle, no qual a duração média de analgesia foi de 35,9 ± 21,6 minutos (p < 0,05) e a porcentagem de pacientes com analgesia efetiva foi de 69,6% (p < 0,05). CONCLUSÕES: A adição de sufentanil à bupivacaína hiperbárica melhora a qualidade e prolonga a duração da analgesia. Quando associado a 2,5 mg de bupivacaína hiperbárica, não há vantagem de se administrar dose superior a 2,5 µg de sufentanil para alívio da dor do trabalho de parto.

ANALGESIA; ANALGÉSICOS; ANALGÉSICOS; ANESTÉSICOS; ANESTÉSICOS; TÉCNICAS ANESTÉSICAS; TÉCNICAS ANESTÉSICAS; TÉCNICAS ANESTÉSICAS; TÉCNICAS ANESTÉSICAS

SCIENTIFIC ARTICLE

Spinal sufentanil associated to hyperbaric bupivacaine: is it possible to decrease opioid dose?^*

Sufentanil subaracnóideo asociado a la bupivacaína hiperbárica para analgesia de parto: es posible reducir la dosis del opioide?

Eduardo Tsuyoshi Yamaguchi, TSA, M.D.^I; José Carlos Almeida Carvalho, TSA, M.D.^II; Ubirajara Sabbag Fonseca, M.D.^III; Jacqueline Toshiko Hirahara, TSA, M.D.^IV; Mônica Maria Siaulys Capel Cardoso, TSA, M.D.^V

^IMédico Colaborador da Disciplina de Anestesiologia da FMUSP. Anestesiologista do Hospital e Maternidade Santa Joana

^IIDiretor Científico do Departamento de Anestesiologia do Hospital e Maternidade Santa Joana

^IIIME₂ da Disciplina de Anestesiologia da FMUSP

^IVME₃ da Disciplina de Anestesiologia da FMUSP. Anestesiologista do Hospital e Maternidade Santa Joana

^VDoutora em Anestesiologia pela FMUSP. Médica Supervisora da Anestesia Obstétrica do HCFMUSP. Anestesiologista do Hospital e Maternidade Santa Joana

^{Correspondence}

SUMMARY

BACKGROUND AND OBJECTIVES: The association of isobaric bupivacaine to lower spinal sufentanil dose provides satisfactory analgesia and lower incidence of side effects. This study aimed at evaluating quality of analgesia and incidence of side effects of decreased spinal sufentanil doses associated to hyperbaric bupivacaine for labor analgesia.

METHODS: Participated in this study 69 healthy term pregnant patients in active labor. Patients were randomly allocated in three groups receiving spinal combination of 2.5 mg hyperbaric bupivacaine and 1 mL saline solution (Control Group); 2.5 mg hyperbaric bupivacaine and 2.5 µg sufentanil (S2.5 Group) or 2.5 mg hyperbaric bupivacaine and 5 µg sufentanil (S5 Group). Pain, using a visual analogue scale (VAS), and side effects were evaluated at 5-minute intervals for the first 15 minutes and then at 15-minute interval until delivery. Study would end with delivery or when patient requested rescue analgesia (VAS > 3 cm).

RESULTS: Groups S2.5 and S5 presented longer analgesia duration (67.2 ± 38.6 and 78.9 ± 38.7 minutes, respectively) and a larger number of patients with effective analgesia (100% and 95.6%, respectively) as compared to Control group where mean analgesia duration was 35.9 ± 21.6 minutes (p < 0.05) with 69.6% of patients with effective analgesia (p < 0.05).

CONCLUSIONS: The association of sufentanil to hyperbaric bupivacaine improves quality and prolongs analgesia duration. When associated to 2.5 mg hyperbaric bupivacaine, there is no benefit in administering more than 2.5 µg of sufentanil for labor pain relief.

Key Words: ANALGESIA: labor; ANALGESICS, Opioids: sufentanil; ANESTHETICS, Local: bupivacaine; ANESTHETIC TECHNIQUES, Regional: combined, epidural, spinal block

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La adición de bupivacaína isobárica a dosis menores de sufentanil por vía subaracnóidea promueve analgesia de cualidad satisfactoria, con menor incidencia de efectos colaterales. El objetivo del estudio fue evaluar la calidad de la analgesia y la incidencia de efectos colaterales de dosis reducidas de sufentanil subaracnóideo asociados a bupivacaína hiperbárica en analgesia de parto.

MÉTODO: Fueron estudiadas prospectivamente 69 embarazadas de término en trabajo de parto. Las embarazadas fueron aleatoriamente divididas en tres grupos que recibieron, en el espacio subaracnóideo, la combinación de 2,5 mg de bupivacaína hiperbárica y 1 mL de solución fisiológica (Grupo Control); 2,5 mg de bupivacaína hiperbárica y 2,5 µg de sufentanil (Grupo S2,5) o 2,5 mg de bupivacaína hiperbárica y 5 µg de sufentanil (Grupo S5). El dolor, de acuerdo con la escala analógico visual (EAV) de dolor y la incidencia de efectos colaterales fueron evaluadas a cada 5 minutos en los primeros quince minutos y a seguir a cada 15 minutos hasta el nacimiento. El estudio terminaba con el nacimiento, o cuando la paciente solicitaba medicación analgésica de rescate (EAV > 3 cm).

RESULTADOS: Los grupos S2,5 y S5 presentaron mayor duración de analgesia (67,2 ± 38,6 y 78,9 ± 38,7 minutos, respectivamente) y mayor porcentaje de pacientes con analgesia efectiva (100% y 95,6%, respectivamente) que el grupo Control, en el cual la duración media de analgesia fue de 35,9 ± 21,6 minutos (p < 0,05) y el porcentaje de pacientes con analgesia efectiva fue de 69,6% (p < 0,05).

CONCLUSIONES: La adición de sufentanil a la bupivacaína hiperbárica mejora la calidad y prolonga la duración de la analgesia. Cuando asociado a 2,5 mg de bupivacaína hiperbárica, no hay ventaja de administrar dosis superior a 2,5 µg de sufentanil para alivio del dolor del trabajo de parto.

INTRODUCTION

Sufentanil is a widely used opioid for labor analgesia for its fast onset and high analgesic potency. Herman et al. ¹ and Arkoosh et al. ² have shown that sufentanil's DE₅₀ for spinal labor analgesia as a single drug is 2.6 µg (dose needed for inducing analgesia in 50% of patients) and that DE₉₅ is 8.9 µg (dose needed for inducing analgesia in 95% of patients).

The association of opioids to local analgesics is common in labor analgesia. The additive and synergistic effect of such drugs provides better quality analgesia with lower incidence of side effects ³.

A dose-response study with the combination of sufentanil and isobaric bupivacaine has shown that, when associated to 2.5 mg bupivacaine, spinal sufentanil dose may be decreased from 10 µg to 2.5 µg decreasing pruritus intensity without impairing analgesia quality ⁴.

Our routine labor analgesia has been the association of spinal sufentanil and hyperbaric bupivacaine. The association of hypobaric sufentanil and hyperbaric bupivacaine results in hyperbaric solution.

Anesthetic solutions baricity may significantly change anesthetic agents spread in the spinal space producing different clinical effects.

This study aimed at evaluating quality of analgesia and incidence of side effects provided by two different spinal sufentanil doses associated to hyperbaric bupivacaine in labor analgesia.

METHODS

After the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo and Hospital e Maternidade Santa Joana Ethics Committee approval, participated in this prospective, randomized and double blind study 69 healthy term pregnant women in active labor without obstetric or fetal complications.

After monitoring with ECG, noninvasive blood pressure and pulse oximetry, patients received volume expansion with 250 mL lactated Ringer' solution. Combined spinal-epidural anesthesia was induced with patients in the sitting position in L₂-L₃ or L₃-L₄ interspace using the needle-through-needle technique. Anesthetic solution was only administered after passive CSF reflux through needle's gun. Epidural catheter was inserted immediately after. After puncture, patients were placed in the supine position with uterine displacement to the left. Anesthetic solutions were prepared by an anesthesiologist not involved with patients care.

When analgesia was requested, patients were randomly distributed in 3 groups receiving:

• Control Group (n = 23): spinal 2.5 mg of 0.5% hyperbaric bupivacaine associated to 1 mL saline solution;

• Group S2.5 (n = 23): spinal 2.5 µg sufentanil associated to 2.5 mg of 0.5% hyperbaric bupivacaine and 0.5 mL saline solution;

• Group S5 (n = 23): spinal 5 µg sufentanil associated to 2.5 mg of 0.5% hyperbaric bupivacaine.

Pain and possible side effects (nausea, vomiting, pruritus) were evaluated at analgesia induction, at 5-minute intervals in the following 15 minutes and then at 15-minute intervals until delivery.

Pain was evaluated through a visual analog scale (VAS) from 0 to 10 cm (0 = no pain and 10 = unbearable pain) and by an anesthesiologist blind to the group the patient belonged to. After first 15 minutes, if pain was higher than 3 cm, 4 mL bolus of increasing 0.125% and 0.25% bupivacaine concentrations were administered through epidural catheter at 15-minute intervals until pain was controlled (below 3 cm).

The study was ended at first rescue analgesia request or at delivery.

For statistical analysis ANOVA was used to compare age, weight, height, initial dilatation and analgesia duration among groups; Kruskal-Wallis test was used for initial VAS and fifteen minutes after spinal injection; Chi-square test was used for delivery before rescue analgesia; and Fisher's Exact test was used to compare nausea, vomiting, pruritus and rescue analgesia in the first 15 minutes, considering significant p < 0.05.

RESULTS

Groups were similar in age, weight, height (Table I) and mean initial cervical dilatation (Table II).

Brazilian Journal of Anesthesiology, 2004; 54: 2: 145 - 152

Spinal sufentanil associated to hyperbaric bupivacaine: is it possible to decrease opioid dose?

Eduardo Tsuyoshi Yamaguchi; José Carlos Almeida Carvalho; Ubirajara Sabbag Fonseca;

Jacqueline Toshiko Hirahara; Mônica Maria Siaulys Capel Cardoso

Brazilian Journal of Anesthesiology, 2004; 54: 2: 145 - 152

Spinal sufentanil associated to hyperbaric bupivacaine: is it possible to decrease opioid dose?

Eduardo Tsuyoshi Yamaguchi; José Carlos Almeida Carvalho; Ubirajara Sabbag Fonseca;

Jacqueline Toshiko Hirahara; Mônica Maria Siaulys Capel Cardoso

Groups receiving 2.5 µg or 5 µg sufentanil had longer analgesia duration with lower need for rescue analgesia after the first 15 minutes as compared to Control Group (Table II).

Figure 1 shows the percentage of patients with VAS below 3 cm as a function of time. There has been a higher number of deliveries before rescue analgesia in Groups S2.5 and S5 as compared to Control Group (Figure 2).

Brazilian Journal of Anesthesiology, 2004; 54: 2: 145 - 152

Spinal sufentanil associated to hyperbaric bupivacaine: is it possible to decrease opioid dose?

Eduardo Tsuyoshi Yamaguchi; José Carlos Almeida Carvalho; Ubirajara Sabbag Fonseca;

Jacqueline Toshiko Hirahara; Mônica Maria Siaulys Capel Cardoso

Brazilian Journal of Anesthesiology, 2004; 54: 2: 145 - 152

Spinal sufentanil associated to hyperbaric bupivacaine: is it possible to decrease opioid dose?

Eduardo Tsuyoshi Yamaguchi; José Carlos Almeida Carvalho; Ubirajara Sabbag Fonseca;

Jacqueline Toshiko Hirahara; Mônica Maria Siaulys Capel Cardoso

Mean VAS scores at analgesia installation were similar among groups. However it has been observed that 15 minutes after initial spinal anesthetic injection, mean pain scores in Control Group were significantly higher as compared to groups receiving 2.5 and 5 µg sufentanil (Figure 3).

Brazilian Journal of Anesthesiology, 2004; 54: 2: 145 - 152

Spinal sufentanil associated to hyperbaric bupivacaine: is it possible to decrease opioid dose?

Eduardo Tsuyoshi Yamaguchi; José Carlos Almeida Carvalho; Ubirajara Sabbag Fonseca;

Jacqueline Toshiko Hirahara; Mônica Maria Siaulys Capel Cardoso

There were no statistically significant differences in nausea and vomiting among groups. Mild pruritus was higher in groups S2.5 and S5 as compared to Control Group. There has been severe pruritus in two Group S5 patients without statistical difference in this variable among groups (Table III).

Brazilian Journal of Anesthesiology, 2004; 54: 2: 145 - 152

Spinal sufentanil associated to hyperbaric bupivacaine: is it possible to decrease opioid dose?

Eduardo Tsuyoshi Yamaguchi; José Carlos Almeida Carvalho; Ubirajara Sabbag Fonseca;

Jacqueline Toshiko Hirahara; Mônica Maria Siaulys Capel Cardoso

DISCUSSION

Our results have shown that the association of 2.5 µg or 5 µg sufentanil to spinal hyperbaric bupivacaine for labor analgesia provides longer duration and better analgesia as compared to local anesthetic alone. These data are in line with Wong et al. ⁴ who have studied dose-response of opioid/local anesthetics combination and have also concluded that the association of different sufentanil doses (0.25; 5; 7.5 and 10 µg) to isobaric bupivacaine would improve quality and prolong labor analgesia duration.

The major difference between both studies is the baricity of spinal local anesthetics. The association of 0.5 or 1 mL sufentanil (density = 0.9933 g.mL^-1) to 0.5 mL of 0.5% hyperbaric bupivacaine (density = 1.026 g.mL^-1) at 20 ºC produces hyperbaric solutions (density = 1.002935 g.mL^-1). Wong et al. ⁴ in associating different sufentanil doses to hypobaric bupivacaine, have worked with isobaric solutions.

It is known that changes in baricity of spinal anesthetic solutions, especially sufentanil, may significantly change anesthetic solution spread dynamics in the spinal space and, as a consequence, its clinical effects ⁵.

Ferouz et al. ⁶ have shown that 1 mL of 10% dextrose associated to 1 mL sufentanil (10 µg.mL^-1) thus producing hyperbaric sufentanil solution, would determine less side effects (especially severe pruritus) but would impair analgesic quality. So, they have suggested that side effects would depend on the supraspinal action of opioids and that the analgesic action would depend both on the spinal and supraspinal action.

Although not directly comparing analgesic efficacy of hypobaric and hyperbaric sufentanil-containing solutions to bupivacaine, it is possible that potential analgesia quality impairment caused by hyperbaric sufentanil has been corrected by the association to local anesthetics, since both drugs would have additive and synergistic effects on pain.

It is our routine to administer opioids associated to local anesthetics, since in our practice labor analgesia is often induced at the end of the first labor stage and beginning of the second. Previous studies have shown that spinal opioids alone are not effective in relieving labor pain, especially as the patient gets closer to the second labor stage ^7-10.

However it is worth mentioning that in this study analgesia was always based on patients' request and not on cervical dilatation. Although mean cervical dilatation at analgesia request was approximately 5 cm, there has been wide individual variation (1 to 9 cm), which reflects individual differences in pain tolerance during labor.

We decided not to perform the test dose with 3 mL of 1.5% lidocaine and 1:200,000 epinephrine immediately after spinal anesthetic injection and further epidural catheter insertion as proposed by Wong et al. ⁴ because test dose could contribute to analgesia.

Test dose could improve the quality of analgesia with low spinal sufentanil and bupivacaine doses by the direct action of lidocaine in the epidural space, or indirectly, by interfering with spread dynamics of recently injected anesthetics and not yet fixed within the spinal space (mass effect and transmission of epidural pressure to the spinal space).

Cardoso et al. ¹¹, evaluating epidural pressure changes promoted by local anesthetics injected in different volumes and rates, have shown that even low volumes such as those used for test dose, when rapidly injected, determine higher epidural space peaks than the administration of higher volumes at lower rates.

It should be also mentioned that instantaneous checking of correct epidural catheter position does not assure its permanence in the same place during future manipulations. There are in the literature several cases of intravascular and spinal migration of epidural catheters previously well positioned. In addition, in labor analgesia, complications of intravascular local anesthetic injections by epidural catheter malposition are uncommon, because the anesthesiologist is working with extremely low local anesthetic doses and concentrations.

As to side effects, it has been observed that when sufentanil dose was decreased from 5 to 2.5 µg, there has been no change in nausea, vomiting, mild pruritus, severe pruritus and analgesia duration. These data are in line with Wong et al. ⁴ who have also found no differences in the incidence of nausea, vomiting, pruritus and analgesia duration after the administration of different spinal sufentanil doses (2.5; 5; 7.5 and 10 µg). In both studies, differences in the incidence of side effects and analgesia duration were only found between groups receiving sufentanil associated to bupivacaine as compared to control groups where labor analgesia was induced with local anesthetics alone.

It is however important to stress that sample size was not enough to show possible differences between both sufentanil doses. Power analysis for side effects-related variables has shown that in order to detect approximately 13% difference in pruritus, two groups of 198 patients each would have to be studied.

It has also been observed that the number of deliveries before the need for epidural complementation was higher in groups receiving sufentanil as compared to control. This fact does not necessarily indicate faster cervical dilatation with sufentanil, but is possibly related to longer analgesia duration in those groups as compared to control group.

Although respiratory depression has already been reported with spinal sufentanil ^12-14, we have not observed respiratory depression after spinal sufentanil and although the small sample size to draw any conclusion, it is possible that factors contributing for the absence of such complication were: non utilization of any other systemic drug depressing central nervous system; anesthetic solutions were prepared as from sufentanil's parent solution for spinal use, which contains just 5 µg of the drug per mL and not as from the solution for intravenous use, which contains 50 µg of the drug per mL (thus preventing potential dilution errors); sufentanil doses used in our study were lower (2.5 and 5 µg) than those used when respiratory depression has been observed (10 µg); and the use of hyperbaric solutions which probably limit cephalad spread of drugs to the spinal space ⁶.

In conclusion, the association of different sufentanil doses to spinal hyperbaric bupivacaine improves labor analgesia quality and duration. When associated to 2.5 mg hyperbaric bupivacaine there is no advantage in administering sufentanil doses higher than 2.5 µg.

REFERENCES

Apresentado (Submitted) em 28 de abril de 2003

Aceito (Accepted) para publicação em 17 de julho 2003

• 01. Herman NL, Calicott R, Van Decar TK et al - Determination of the dose-response relationship for intrathecal sufentanil in laboring patients. Anesth Analg, 1997;84:1256-1261.
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• 04. Wong CA, Scavone BM, Loffredi M et al - The dose-response of intrathecal sufentanil added to bupivacaine for labor analgesia. Anesthesiology, 2000;92:1553-1558.
• 05. Nicol ME, Holdcroft A - Density of intrathecal agents. Br J Anaesth, 1992;68:60-63.
• 06. Ferouz F, Norris MC, Arkoosh VA et al - Baricity, needle direction, and intrathecal sufentanil labor analgesia. Anesthesiology, 1997;86:592-598.
• 07. Camann WR, Denney RA, Holby ED et al - A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia. Anesthesiology, 1992;77:884-887.
• 08. Camann WR, Minzter BH, Denney RA et al - Intrathecal sufentanil for labor analgesia. Effects of added epinephrine. Anesthesiology, 1993;78:870-874.
• 09. Honet JE, Arkoosh VA, Norris MC et al - Comparison among intrathecal fentanyl, meperidine, and sufentanil for labor analgesia. Anesth Analg, 1992;75:734-739.
• 10. Norris MC, Fogel ST, Holtmann B et al - Intrathecal sufentanil (5 vs. 10 µg) for labor analgesia: efficacy and side effects. Reg Anesth Pain Med, 1998;23:252-257.
• 11. Cardoso MMSC, Carvalho JCA - Epidural pressures and spread of 2% lidocaine in the epidural space: influence of volume and speed of injection of the local anesthetic solution. Reg Anesth, 1998;23:14-19.
• 12. Fournier R, Gamulin Z, Van Gessel E - Respiratory depression after 5 µg of intrathecal sufentanil. Anesth Analg, 1998;87: 1377-1378.
• 13. Hays RL, Palmer CM - Respiratory depression after intrathecal sufentanil during labor. Anesthesiology, 1994;81:511-512.
• 14. Carvalho JCA - Respiratory arrest following intrathecal sufentanil. Can J Anesth, 1999;46:198-199.

Correspondence to

Dra. Mônica Maria Siaulys Capel Cardoso

Av. Dr. Enéas de Carvalho Aguiar, 255

8º andar PAMB - Divisão de Anestesiologia

05403-900 São Paulo, SP

*

Recebido do (

Received from) Departamento de Anestesiologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP) e do Hospital e Maternidade Santa Joana

Publication Dates

• Publication in this collection
  29 June 2004
• Date of issue
  Apr 2004

History

• Accepted
  17 July 2003
• Received
  28 Apr 2003