S1 DETERMINATION OF THE DOSERESPONSE RELATIONSHIP OF SPINAL BUPIVACAINE

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Abstracts of free papers presented at the annual meeting of the

S1


Determination of the dose-response relationship of spinal bupivacaine, levobupivacaine and ropivacaine, combined with sufentanil, during anaesthesia for caesarean section

E Roofthooft, R Dreelinck, J Dubois, N Berends,
M Van de Velde

Department of Anesthesiology, UZ Leuven, Belgium

Introduction: Ropivacaine (R) and levobupivacaine (L) are less toxic and produce less motor block then bupivacaine (B). Reduced toxicity and increased motor-sensory separation must be evaluated in the light of the relative potency of the drugs. Recently, the full dose- response relation of R, L and B was described during intrathecal labour analgesia.1 R and L were found to be less potent then B. In labour, many factors influence pain intensity. The response to surgery might better allow investigators to describe the dose-response relationship. This study determines the dose-response relationship of spinal L, R and B when used to achieve surgical anaesthesia for caesarean section.

Method: Following ethics committee approval and written consent, 450 term patients with singleton pregnancies undergoing elective caesarean section were included in a blinded, randomised trial. Combined spinal-epidural anaesthesia was performed using intrathecal L, B or R in doses of 5.0, 6.25, 7.5, 8.75, 10 or 11.25 mg, always combined with sufentanil 2.5 μg. Patients were defined responders to anaesthesia if adequate anaesthesia was reached within 15 min and persisted for 60 min. Adequate anaesthesia was defined as insensitivity to cold up to T2 and no need for anaesthetic supplementation. Patient demographics, obstetrical data, haemodynamics, maternal and fetal side effects and pain scores were noted. Group-specific dose-response curves were constructed using a probit regression model. ED50 and ED95 were calculated. A logistic regression model was used to check the sensitivity of the results and a likelihood-ratio test to compare the dose-response curves of L, R and B.

Results: see table:


ED50 (mg) (95% CI)

ED95 (mg) (95% CI)

B

5.417 (4.398-6.028)

8.633 (7.876-10.104)

L

7.246 (6.145-8.064)

13.277 (11.584-17.102)

R

7.512 (6.743-8.178)

12.328 (11.077-14.706)

B was significantly more potent then L and R, whilst R and L were of similar potency.

Discussion: Based on the present dose-response study, intrathecal L and R, combined with sufentanil, are less potent then B when used for anaesthesia during caesarean section. R and L are of similar potency.

Reference

1 Van de Velde M, Dreelinck R, Dubois J, et al. Determination of the full dose-response relation of intrathecal bupivacaine, levobupivacaine, and ropivacaine, combined with sufentanil, for labor analgesia. Anesthesiology 2007; 106: 149-56.

Stability of adrenaline in pH-adjusted lidocaine

J Allam, H Gill,* C Tuleu,* P Knowlden, E Smith, S M Yentis

Chelsea and Westminster Hospital, London, UK and *The School of Pharmacy, University of London, UK

Introduction: Addition of bicarbonate speeds the onset of epidural lidocaine for emergency caesarean section.1 Adrenaline is often added to this mixture to reduce toxicity and prolong the block.2 However, adrenaline degrades completely 24 h after mixing,3 but there are no data for <24 h. We studied the degradation of adrenaline at intervals after combining the three ingredients.

Method: We prepared three syringes as follows: 2 mL of 8.4% sodium bicarbonate was added to 20 mL of lidocaine; 2 mL of this mixture was discarded and 0.1 mL of 1:1000 adrenaline added. The solution was stored at 24°C, unprotected from ambient artificial light. Adrenaline and lidocaine were assayed by high-performance liquid chromatography with ultraviolet detection at 0, 2, 4, 6 and 20 h. Results were analysed with repeated measures ANOVA, P <0.05 indicating statistical significance.

Results: Adrenaline concentrations in the bicarbonated mixture significantly decreased (P <0.0001) as shown below. Lidocaine concentrations were unchanged.

Table. Mean ± SD decrease in adrenaline concentration (as proportion of initial) at intervals after preparation.

0 h

0%

2 h

4.1 ± 0.6%

4 h

12.4 ± 2.1%

6 h

27 ± 3.6%

20 h

100%

Conclusion: Anecdotal enquiries suggest that anaesthetists who use pH-adjusted lidocaine/adrenaline for epidural top-ups commonly prepare the mixture well in advance of its use, despite a lack of data about its stability between 0 and 24 h. Our study suggests that this practice is inadvisable, especially if the mixture is kept in bright light and/or higher temperatures, when faster degradation would be expected (let alone issues over sterility). However, if kept away from bright light and at 24°C or lower, our results suggest that over 90% of the adrenaline is still present within the first 2 h of preparation.

References

1. Lam DT, Ngan Kee WD, Khaw KS. Extension of epidural blockade in labour for emergency Caesarean section using 2% lidocaine with epinephrine and fentanyl, with or without alkalinisation. Anaesthesia 2001; 56: 790-4.

2. Regan K, O’Sullivan G. Extension of epidural blockade for emergency caesarean section: a survey of UK practice. Int J Obstet Anesth 2006; 15: S7.

3. Robinson J, Fernando R, Sun Wai WYS, Reynolds F. Chemical stability of bupivacaine, lidocaine and epinephrine in pH adjusted solutions. Anaesthesia 2000; 55: 853-8.


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Tags: bupivacaine (b)., relationship, determination, doseresponse, spinal, bupivacaine