- Email: [email protected]
COMPARISON OF PLAIN AND ALKALINIZED LOCAL ANAESTHETIC MIXTURES OF LIGNOCAINE AND BUPIVACAINE FOR ELECTIVE EXTRADURAL CAESAREAN SECTION
British Journal of Anaesthesia 1991; 67: 699-703
COMPARISON OF PLAIN AND ALKALINIZED LOCAL ANAESTHETIC MIXTURES OF LIGNOCAINE AND BUPIVACAINE FOR ELECTIVE EXTRADURAL CAESAREAN SECTION R. FERNANDO AND H. M. JONES
We have examined a local anaesthetic mixture of 0.5% bupivacaine 10 ml and 2% lignocaine 10 ml with adrenaline 1 in 200000, to which 8.4% sodium bicarbonate 2ml was added, for extradural Caesarean section. The alkalinized mixture of local anaesthetics produced a block of more rapid onset and density than a mixture of bupivacaine and lignocaine alone (? < 0.001). KEY WORDS Anaesthesia: obstetric. Anaesthetics, local: alkalinized mixture, bupivacaine. lignocaine. Anaesthetic techniques: extradural.
Plain 0.5% bupivacaine and 2% lignocaine with adrenaline 1 in 200000 are popular agents for extradural Caesarean section [12, 13], but the former has potential cardiotoxicity and the latter provides poor quality extradural block [14, 15]. Mixtures of local anaesthetics have obvious advantages and have been used for several years in nonobstetric practice [16]. The dose of bupivacaine may be reduced, thereby reducing cardiotoxicity [17]. Recently, Howell and colleagues have used a mixture of 2% lignocaine 10 ml and 0.5% bupivacaine 10 ml to which adrenaline had been added to achieve a concentration of 1 in 200000 for obstetric use [14]. However, the onset time for this mixture (T4-S5 sensory block) did not differ significantly from that of three other solutions (mean onset time 24.6 min). There is some evidence to suggest that alkalinizing local anaesthetic solutions results in improved efficacy, by increasing the amount of lipid soluble form in solution [18]. We have therefore examined the use of an alkalinized mixture of lignocaine and bupivacaine in extradural block for Caesarean section.
The use of extradural block for Caesarean section has three main disadvantages: a slow onset time commonly ranging from 20 to 50 min to achieve a sensory block from T4 to S5 [1-3], a density of block not comparable to that of spinal anaesthesia [4] and, occasionally, a need for inducing general anaesthesia. Large volumes of local anaesthetic may be used, exceeding the recommended dose [5]. Spinal anaesthesia offers the advantages of rapid onset and good quality [6,7], but postdural PATIENTS AND METHODS puncture headache remains a disadvantage, even with 26-gauge spinal needles [6]. Thirty-gauge We prepared a solution of 2% lignocaine 10 ml needles may reduce the incidence of headache, but and 0.5% bupivacaine 10 ml to which 0.1 ml of may be associated with technical difficulties [8]. adrenaline 1 in 1000 was added to achieve a conPencil point needles are said to separate dural fibres and to reduce the incidence of headache [9]. Extradural block for obstetric anaesthesia R. FERNANDO*, F.F.A.R.C.S.I., F.C.ANAES.; H . M . J O N E S , would be enhanced if a local anaesthetic agent F.C.ANAES. ; Department of Anaesthetics, Royal Gwent Hoswere available which provided a block of rapid pital, Newport, Gwent NPT 2UB. Accepted for Publication: 23, 1991. onset, good quality and of adequate duration June •Present address: Department of Anaesthetics, Hammerusing the minimum dose, so that toxicity is smith Hospital, Du Cane Road, London. avoided [5, 10-12]. Correspondence to H. M. J.
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 22, 2015
SUMMARY
700
TABLE I. Bromage motor block 1—No block 2—Partial block
3—Almost complete block 4—Complete block
Full flexion of knees and feet. Just able to flex knees, but still full flexion of feet possible. Unable to flex knees, flexion, of feet possible. Unable to flex knees or feet.
with no sign of catheter misplacement, another 18 ml of test solution was injected over 2 min. The onset of sensory block was assessed every 1 min by loss of cold sensation to ethyl chloride spray, and motor block by the loss of leg muscle power on a four-point Bromage Scale (table I). The position of the patient was changed as deemed appropriate to achieve a bilateral sensory block (T4—S5) as quickly as possible. Finally, the patient was turned supine with left lateral tilt when the sensory block was adequate. If, 15 min after the end of die main injection of 18 ml, the thoracic or sacral level was considered inadequate, further increments of a 50:50 mixture of 2 % lignocaine and 0.5 % bupivacaine with adrenaline 1 in 200000 were given, and the patient's position changed if necessary. In all patients, ephedrine 30 mg was added to the third 500-ml container of Hartmann's solution. Hypotension was minimized by infusing this solution to ensure the systolic arterial pressure was maintained greater than 100 mm Hg. An upper sensory level of T4 and a lower level of S5 were considered adequate for surgery. The onset time was defined as the time from giving the test dose to the patient being ready for surgery. Any pain or discomfort during die procedure was treated with supplementary extradural solution and i.v. or extradural opioids after delivery of the baby. Fentanyl 100 ug in 8 ml of normal saline was administered via the extradural catheter at the completion of surgery for postoperative pain relief. At the end of the procedure, both anaesthetist and patient were asked to answer preset questions to evaluate die extradural block. The anaesdietist rated the quality of the block as follows: excellent = no pain or discomfort felt; very good = only mild discomfort was felt, not requiring treatment; good = pain or discomfort requiring further local anaesthetic or extradural fentanyl; fair = in addition to further local an-
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 22, 2015
centration of 1 in 200000. We then added 0.5-ml aliquots of 8.4% sodium bicarbonate to this mixture to optimize the pH without causing precipitation. pH was measured using a Kent E1L 7035 electrode subjected to a two-point calibration using commercially available buffered pH solutions. The final mixture consisted of 2 % lignocaine 10 ml and 0.5% bupivacaine 10 ml, 0.1ml of adrenaline 1 in 1000 and 2 ml of 8.4% sodium bicarbonate. After Ethics Committee approval and informed patient consent had been obtained, we studied 20 healthy women undergoing elective Caesarean section. They were allocated randomly in a double-blind design to receive one of two solutions: a 50:50 mixture of 0.5% bupivacaine and 2 % lignocaine with adrenaline 1 in 200000 to which 8.4 % sodium bicarbonate 2 ml had been added, or a 50:50 mixture of 0.5% bupivacaine and 2 % lignocaine with adrenaline 1 in 200000 to which 2 ml of normal saline had been added. One millilitre of each solution was kept for pH analysis at the end of the procedure. Hence 21 ml of each solution was used initially. All solutions were used at room temperature. The anaesthetist responsible for the conduct of the extradural block prepared die initial solution of 2% lignocaine 10 ml, 0.5% bupivacaine 10 ml and 0.1 ml of adrenaline 1 in 1000. A second anaesthetist who was not involved directly with clinical management or testing of the patient drew up either 2 ml of 8.4 % sodium bicarbonate or 2 ml of normal saline, according to the randomization envelopes. The first anaesthetist then added the 2 ml of solution into the previously prepared "20 ml" syringe with the local anaesthetic mixture. At no time was the first anaesthetist aware of the contents of the 2-ml syringe given to him. One millilitre of this final solution was withdrawn from the syringe and kept for pH analysis. After routine prophylaxis with ranitidine and oral antacid, cannulation of a vein and attachment of non-invasive cardiovascular monitoring, the patient was placed in the sitting position. The extradural space was located by a 16-gauge Tuohy needle at the L2-3 or L3-4 interspace using loss of resistance to air and 3 cm of catheter was left in the extraduraJ space. After an i.v. preload of Hartmann's solution 1 litre, 3 ml of the extradural solution was injected through the catheter with the patient in the left lateral position. After 5 min,
BRITISH JOURNAL OF ANAESTHESIA
ALKALINIZED LOCAL ANAESTHETICS IN OBSTETRICS aesthetic and extradural fentanyl, i.v. alfentanil 0.2 mg was required; poor = general anaesthesia had to be induced.
TABLE IV. Number of patients in each group experiencing pain or discomfort during their Caesarcan section
Statistical analysis To compare the sensory and motor block onset times between the two groups, a Mann—Whitney test was used. Fisher Exact test was used to evaluate tables IV and V. P < 0.05 was regarded as statistically significant.
Alkalinized group
Plain group
10 0 0 0
4 2 4 0
None Mild Moderate Severe
TABLE V. Anaesthetist' 5 assessment of the extradural block
RESULTS
TABLE II. Patient data (mean Alkalinized group (n = 10)
Plain group (n = 10)
26.3(3.16) 158.9(5.62) 74.8(11.25) 54.9(14.33)
28.2 (4.26) 158.7 (5.40) 70.5 (9.34) 41.4(12.47)
Alkalinized group
Plain group
10 0 0 0 0
4 2 2 2 0
Excellent Very good Good Fair Poor
Only 21 ml of local anaesthetic solution was used for all 10 patients in the pH adjusted group, whereas three patients in the control group required supplementary local anaesthetic to achieve a sensory block to T4. There was no symptomatic evidence of systemic toxicity in any patient. None of the patients in the pH-adjusted group felt any pain or discomfort during the procedure (P = 0.011) (table IV). Six patients in the control group required supplementation. Assessment of the extradural block by both the anaesthetist and the patient was completed at the end of the procedure. All 10 patients in the pHadjusted group were rated as excellent by the anaesthetist (P = 0.011) (table V). All 20 patients were highly satisfied with their extradural block.
TABLE III. Onset times for sensory and Bromage Scale 3 motor block. *P < 0.001 compared with plain group sensory block; ** P < 0.002 compared with plain group motor block Patient number 1 Alkalinized group Sensory onset (min)* Bromage 3 (min)** pH Plain group Sensory onset (min) Bromage 3 (min) PH
2
3
4
5
6
7
8
9
10
Mean
12 15 7. 12
13 14 7.12
13 15 7.20
14 14 7.10
13 17 7.20
14 15 7.20
13 15 7.25
12 16 7.30
13 18 7. 30
10 16 7.25
12.7 15.5
17 20 5. 30
20 22 4.70
20 25 4.90
13 15 5.00
21 23 4.60
21 26 4.60
22 25 5.00
23 23 4.90
24 26 5. 10
38 40 5.00
21.9 24.5
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 22, 2015
The groups were comparable in age, weight, height and duration of surgery (table II). There was a statistically significant difference (P < 0.001) between the two groups for onset time to sensory block T4-S5. Mean sensory onset time in the pH adjusted group was 12.7 (SD 1.16) min (range 10-14 min), whereas that in the control group was 21.9 (6.47) min (range 1338 min). The onset time to Bromage Scale 3 motor block was also significantly faster in the pH adjusted group (P < 0.002). The mean time in the alkalinized group was 15.5 (1.27) min (range 14-18 min), compared with 24.5 (6.38) min (range 15—40 min) in the control group (table III). The highest block in both groups was T2.
Age (yr) Height (cm) Weight (kg) Duration of surgery (min)
701
BRITISH JOURNAL OF ANAESTHESIA
702
In both groups, cardiovascular stability was achieved with the crystalloid preload and the ephedrine infusion. All the babies delivered had Apgar scores greater than 7 at 1 min and 9 or more at 5 min. None needed resuscitation. The pH of each solution was tested using a digital pH meter at the end of the procedure. The average pH of the alkalinized group was 7.20 (range 7.10-7.30); that of the control group was 4.91 (range 4.60-5.30) (P < 0.001).
Alkalinization of local anaesthetic solutions to speed up the onset of action has been used with varying degrees of success by several workers [18-20]. Another method to reduce the onset time has been the production of carbonated solution [21-23]. For example, lignocaine has been acidified by carbonation and is produced commercially by Astra Pharmaceuticals. Early work by Bromage indicated the superiority of such carbonated solutions compared with plain lignocaine in open studies in which a single local anaesthetic bolus was injected [22, 23]. Alkalinized solutions of 2 % lignocaine with adrenaline 1 in 400000 were compared with plain and carbonated lignocaine solutions for elective Caesarean section by Liepert and colleagues [21], who did not find any significant difference in the onset times (approximately 20 min) for all three groups. However, an incremental technique was used to deliver the local anaesthetic into the extradural space. We chose to use a bolus technique after a test dose had been given, as differences in onset times should be more apparent than with an incremental method. We found that the alkalinized mixture consistently had a more rapid onset of action which often reduced the waiting time to surgery by 50%. In addition, the extradural block was thought to be extremely dense in nature and provided good operating conditions without any patient experiencing pain or discomfort during the procedure. The onset times for the control mixture were comparable to those reported by Howell and colleagues [14]. Routine use of such a mixture has some disadvantages, including a potential for error in mixing four different drugs and unknown stability of the resultant solution. At present we mix the solutions immediately before use, as we have no data on the stability of this alkalinized mixture.
ACKNOWLEDGEMENTS We thank Dr R. Newcombe, Senior Lecturer in Medical Statistics, University Hospital of Wales for evaluating the data.
REFERENCES 1. Laishley RS, Morgan BM. A single dose epidural technique for Caesarean section. A comparison between 0.5% bupivacaine plain and 0.5% bupivacaine with adrenaline. Anaesthesia 1988; 43: 100-103. 2. Thorburn J, Moir D D . Epidural analgesia for elective Caesarean section technique and its assessment. Anaesthesia 1980; 35: 3-6. 3. Paech MJ, Westmore MD, Speirs HM. A double-blind comparison of epidural bupivacaine and bupivacaine/ fentanyl for Caesarean section. Anaesthesia and Intensive Care 1990; 18: 22-30. 4. Russell IFC. Spinal is better than epidural anaesthesia for elective Caesarean section. In: Morgan B, ed. Controversies in Obstetric Anaesthesia. Scvenoaks: Edward Arnold, 1990; 1-11. 5. Crawford JS, Davies P, Lewis M. Some aspects of epidural block provided for elective Caesarean section. Anaesthesia 1986; 41: 1039-1046. 6. Michie AR, Freeman RM, Dutton DA, Howie HB. Subarachnoid anaesthesia for elective Caesarean section. A comparison of two hyperbaric solution. Anaesthesia 1988; 43: 96-99. 7. Russell IF, Holmquist EL. Subarachnoid analgesia for Caesarean section. A double-blind comparison of plain and hyperbaric 0.5% bupivacaine. British Journal of Anaesthesia 1987; 59: 347-353. 8. Lesser P, Bembridge M, Lyons G, Macdonald R. An evaluation of a 30-gauge needle for spinal anaesthesia for Caesarean section. Anaesthesia 1990; 45: 767-768. 9. Cesarini M, Torrielli R, Lahave F, Mene JM, Cabiro C. Sprotte needle for intrathecal anaesthesia for Caesarean section: incidence of postdural puncture headache. Anaesthesia 1990; 45: 656-658. 10. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 1979; 51: 285-287. 11. Marx GF. Cardiotoxicity of local anesthetics. Anesthesiology 1984; 60: 3-5. 12. Abboud TK, Kim KC, Noueihed R, Kuhnert BR, Der Mardirossian N, Moumdjian J, Sarkis F, Nagappala S. Epidural bupivacaine, chlorprocaine or lidocaine for Cesarean section—maternal and neonatal effects. Anesthesia and Analgesia 1983; 62: 914-919.
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 22, 2015
DISCUSSION
However, alkalinized solutions of bupivacaine and adrenaline have been shown to be stable for up to 6h [24]. It has been suggested that sodium bicarbonate might be added to a premixed syringe of bupivacaine and lignocaine with adrenaline 1 in 200000 using an IMS (International Medication System) type of cartridge.
ALKALINIZED LOCAL ANAESTHETICS IN OBSTETRICS
19. Difazio CA, Carron H, Grosslight KR. Comparison of pH adjusted lidocaine solutions for epidural anesthesia. Anesthesia and Analgesia 1986; 65: 760-764. 20. Tackley RM, Coe AJ. Alkalinised bupivacaine and adrenaline for epidural Caesarean section. Anaesthesia 1988; 43: 1019-1021. 21. Liepert DJ, Mcmorland GH, Gambling DR, Kim HK, Ross PLE. Comparison of lidocaine CO,, 2 % lidocaine hydrochloride, and pH adjusted lidocaine hydrochloride for Caesarean section anaesthesia. Canadian Journal of Anaesthesia 1990; 37: 333-336. 22. Bromage PR. A comparison of the hydrochlonde and carbon dioxide salts of lidocaine and prilocaine in epidural analgesia. Ada Anaesthesiologica Scandinavica 1965; (Suppl. 16): 55-69. 23. Bromage PR. Improved conduction blockade in surgery and obstetrics: carbonated local anaesthetics. Canadian Medical Association Journal 1967; 97: 1377-1384. 24. Bonhomme L, Benhamau D, Martre H, Prcaux N. Chemical stability of bupivacaine and epinephrine in pH adjusted solutions. Anesthesiology 1987; 67: A279.
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 22, 2015
13. Paech MJ. Epidural anaesthesia for Caesarean section: a comparison of 0.5 % bupivacainc and 2 % lignocaine both with adrenaline. Anaesthesia ana" Intensive Care 1988; 16: 187-196. 14. Howell P, Davics W, Wrigley M, Tan P, Morgan B. Comparison of four local extradural anaesthetic solutions for elective Caesarean section. British Journal of Anaesthesia 1990; 65: 648-653. 15. Scott DB, Hibbard BM. Serious non-fatal complications associated with extradural block in obstetric practice. British Journal of Anaesthesia 1990; 64: 537-541. 16. Scow LT, Lips FG, Cousins MJ, Mather LE. Lidocainc and bupivacaine mixtures for epidural blockade. Anesthestology 1982; 56: 177-183. 17. De Jong RH, Bonin JD. Mixtures of local anesthetics are no more toxic than the parent drugs. Anesthesiology 1981; 54: 177-181. 18. McMorland GH, Douglas MJ, Jeffrey WK, Ross PLE, Axelson JE, Kim JHK, Gambling DR, Robertson K. Effect of pH adjusted bupivacaine on onset and duration of epidural analgesia in parturients. Canadian Journal of Anaesthesia 1986; 33: 537-541.
703
COMPARISON OF PLAIN AND ALKALINIZED LOCAL ANAESTHETIC MIXTURES OF LIGNOCAINE AND BUPIVACAINE FOR ELECTIVE EXTRADURAL CAESAREAN SECTION R. FERNANDO AND H. M. JONES
We have examined a local anaesthetic mixture of 0.5% bupivacaine 10 ml and 2% lignocaine 10 ml with adrenaline 1 in 200000, to which 8.4% sodium bicarbonate 2ml was added, for extradural Caesarean section. The alkalinized mixture of local anaesthetics produced a block of more rapid onset and density than a mixture of bupivacaine and lignocaine alone (? < 0.001). KEY WORDS Anaesthesia: obstetric. Anaesthetics, local: alkalinized mixture, bupivacaine. lignocaine. Anaesthetic techniques: extradural.
Plain 0.5% bupivacaine and 2% lignocaine with adrenaline 1 in 200000 are popular agents for extradural Caesarean section [12, 13], but the former has potential cardiotoxicity and the latter provides poor quality extradural block [14, 15]. Mixtures of local anaesthetics have obvious advantages and have been used for several years in nonobstetric practice [16]. The dose of bupivacaine may be reduced, thereby reducing cardiotoxicity [17]. Recently, Howell and colleagues have used a mixture of 2% lignocaine 10 ml and 0.5% bupivacaine 10 ml to which adrenaline had been added to achieve a concentration of 1 in 200000 for obstetric use [14]. However, the onset time for this mixture (T4-S5 sensory block) did not differ significantly from that of three other solutions (mean onset time 24.6 min). There is some evidence to suggest that alkalinizing local anaesthetic solutions results in improved efficacy, by increasing the amount of lipid soluble form in solution [18]. We have therefore examined the use of an alkalinized mixture of lignocaine and bupivacaine in extradural block for Caesarean section.
The use of extradural block for Caesarean section has three main disadvantages: a slow onset time commonly ranging from 20 to 50 min to achieve a sensory block from T4 to S5 [1-3], a density of block not comparable to that of spinal anaesthesia [4] and, occasionally, a need for inducing general anaesthesia. Large volumes of local anaesthetic may be used, exceeding the recommended dose [5]. Spinal anaesthesia offers the advantages of rapid onset and good quality [6,7], but postdural PATIENTS AND METHODS puncture headache remains a disadvantage, even with 26-gauge spinal needles [6]. Thirty-gauge We prepared a solution of 2% lignocaine 10 ml needles may reduce the incidence of headache, but and 0.5% bupivacaine 10 ml to which 0.1 ml of may be associated with technical difficulties [8]. adrenaline 1 in 1000 was added to achieve a conPencil point needles are said to separate dural fibres and to reduce the incidence of headache [9]. Extradural block for obstetric anaesthesia R. FERNANDO*, F.F.A.R.C.S.I., F.C.ANAES.; H . M . J O N E S , would be enhanced if a local anaesthetic agent F.C.ANAES. ; Department of Anaesthetics, Royal Gwent Hoswere available which provided a block of rapid pital, Newport, Gwent NPT 2UB. Accepted for Publication: 23, 1991. onset, good quality and of adequate duration June •Present address: Department of Anaesthetics, Hammerusing the minimum dose, so that toxicity is smith Hospital, Du Cane Road, London. avoided [5, 10-12]. Correspondence to H. M. J.
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 22, 2015
SUMMARY
700
TABLE I. Bromage motor block 1—No block 2—Partial block
3—Almost complete block 4—Complete block
Full flexion of knees and feet. Just able to flex knees, but still full flexion of feet possible. Unable to flex knees, flexion, of feet possible. Unable to flex knees or feet.
with no sign of catheter misplacement, another 18 ml of test solution was injected over 2 min. The onset of sensory block was assessed every 1 min by loss of cold sensation to ethyl chloride spray, and motor block by the loss of leg muscle power on a four-point Bromage Scale (table I). The position of the patient was changed as deemed appropriate to achieve a bilateral sensory block (T4—S5) as quickly as possible. Finally, the patient was turned supine with left lateral tilt when the sensory block was adequate. If, 15 min after the end of die main injection of 18 ml, the thoracic or sacral level was considered inadequate, further increments of a 50:50 mixture of 2 % lignocaine and 0.5 % bupivacaine with adrenaline 1 in 200000 were given, and the patient's position changed if necessary. In all patients, ephedrine 30 mg was added to the third 500-ml container of Hartmann's solution. Hypotension was minimized by infusing this solution to ensure the systolic arterial pressure was maintained greater than 100 mm Hg. An upper sensory level of T4 and a lower level of S5 were considered adequate for surgery. The onset time was defined as the time from giving the test dose to the patient being ready for surgery. Any pain or discomfort during die procedure was treated with supplementary extradural solution and i.v. or extradural opioids after delivery of the baby. Fentanyl 100 ug in 8 ml of normal saline was administered via the extradural catheter at the completion of surgery for postoperative pain relief. At the end of the procedure, both anaesthetist and patient were asked to answer preset questions to evaluate die extradural block. The anaesdietist rated the quality of the block as follows: excellent = no pain or discomfort felt; very good = only mild discomfort was felt, not requiring treatment; good = pain or discomfort requiring further local anaesthetic or extradural fentanyl; fair = in addition to further local an-
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 22, 2015
centration of 1 in 200000. We then added 0.5-ml aliquots of 8.4% sodium bicarbonate to this mixture to optimize the pH without causing precipitation. pH was measured using a Kent E1L 7035 electrode subjected to a two-point calibration using commercially available buffered pH solutions. The final mixture consisted of 2 % lignocaine 10 ml and 0.5% bupivacaine 10 ml, 0.1ml of adrenaline 1 in 1000 and 2 ml of 8.4% sodium bicarbonate. After Ethics Committee approval and informed patient consent had been obtained, we studied 20 healthy women undergoing elective Caesarean section. They were allocated randomly in a double-blind design to receive one of two solutions: a 50:50 mixture of 0.5% bupivacaine and 2 % lignocaine with adrenaline 1 in 200000 to which 8.4 % sodium bicarbonate 2 ml had been added, or a 50:50 mixture of 0.5% bupivacaine and 2 % lignocaine with adrenaline 1 in 200000 to which 2 ml of normal saline had been added. One millilitre of each solution was kept for pH analysis at the end of the procedure. Hence 21 ml of each solution was used initially. All solutions were used at room temperature. The anaesthetist responsible for the conduct of the extradural block prepared die initial solution of 2% lignocaine 10 ml, 0.5% bupivacaine 10 ml and 0.1 ml of adrenaline 1 in 1000. A second anaesthetist who was not involved directly with clinical management or testing of the patient drew up either 2 ml of 8.4 % sodium bicarbonate or 2 ml of normal saline, according to the randomization envelopes. The first anaesthetist then added the 2 ml of solution into the previously prepared "20 ml" syringe with the local anaesthetic mixture. At no time was the first anaesthetist aware of the contents of the 2-ml syringe given to him. One millilitre of this final solution was withdrawn from the syringe and kept for pH analysis. After routine prophylaxis with ranitidine and oral antacid, cannulation of a vein and attachment of non-invasive cardiovascular monitoring, the patient was placed in the sitting position. The extradural space was located by a 16-gauge Tuohy needle at the L2-3 or L3-4 interspace using loss of resistance to air and 3 cm of catheter was left in the extraduraJ space. After an i.v. preload of Hartmann's solution 1 litre, 3 ml of the extradural solution was injected through the catheter with the patient in the left lateral position. After 5 min,
BRITISH JOURNAL OF ANAESTHESIA
ALKALINIZED LOCAL ANAESTHETICS IN OBSTETRICS aesthetic and extradural fentanyl, i.v. alfentanil 0.2 mg was required; poor = general anaesthesia had to be induced.
TABLE IV. Number of patients in each group experiencing pain or discomfort during their Caesarcan section
Statistical analysis To compare the sensory and motor block onset times between the two groups, a Mann—Whitney test was used. Fisher Exact test was used to evaluate tables IV and V. P < 0.05 was regarded as statistically significant.
Alkalinized group
Plain group
10 0 0 0
4 2 4 0
None Mild Moderate Severe
TABLE V. Anaesthetist' 5 assessment of the extradural block
RESULTS
TABLE II. Patient data (mean Alkalinized group (n = 10)
Plain group (n = 10)
26.3(3.16) 158.9(5.62) 74.8(11.25) 54.9(14.33)
28.2 (4.26) 158.7 (5.40) 70.5 (9.34) 41.4(12.47)
Alkalinized group
Plain group
10 0 0 0 0
4 2 2 2 0
Excellent Very good Good Fair Poor
Only 21 ml of local anaesthetic solution was used for all 10 patients in the pH adjusted group, whereas three patients in the control group required supplementary local anaesthetic to achieve a sensory block to T4. There was no symptomatic evidence of systemic toxicity in any patient. None of the patients in the pH-adjusted group felt any pain or discomfort during the procedure (P = 0.011) (table IV). Six patients in the control group required supplementation. Assessment of the extradural block by both the anaesthetist and the patient was completed at the end of the procedure. All 10 patients in the pHadjusted group were rated as excellent by the anaesthetist (P = 0.011) (table V). All 20 patients were highly satisfied with their extradural block.
TABLE III. Onset times for sensory and Bromage Scale 3 motor block. *P < 0.001 compared with plain group sensory block; ** P < 0.002 compared with plain group motor block Patient number 1 Alkalinized group Sensory onset (min)* Bromage 3 (min)** pH Plain group Sensory onset (min) Bromage 3 (min) PH
2
3
4
5
6
7
8
9
10
Mean
12 15 7. 12
13 14 7.12
13 15 7.20
14 14 7.10
13 17 7.20
14 15 7.20
13 15 7.25
12 16 7.30
13 18 7. 30
10 16 7.25
12.7 15.5
17 20 5. 30
20 22 4.70
20 25 4.90
13 15 5.00
21 23 4.60
21 26 4.60
22 25 5.00
23 23 4.90
24 26 5. 10
38 40 5.00
21.9 24.5
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 22, 2015
The groups were comparable in age, weight, height and duration of surgery (table II). There was a statistically significant difference (P < 0.001) between the two groups for onset time to sensory block T4-S5. Mean sensory onset time in the pH adjusted group was 12.7 (SD 1.16) min (range 10-14 min), whereas that in the control group was 21.9 (6.47) min (range 1338 min). The onset time to Bromage Scale 3 motor block was also significantly faster in the pH adjusted group (P < 0.002). The mean time in the alkalinized group was 15.5 (1.27) min (range 14-18 min), compared with 24.5 (6.38) min (range 15—40 min) in the control group (table III). The highest block in both groups was T2.
Age (yr) Height (cm) Weight (kg) Duration of surgery (min)
701
BRITISH JOURNAL OF ANAESTHESIA
702
In both groups, cardiovascular stability was achieved with the crystalloid preload and the ephedrine infusion. All the babies delivered had Apgar scores greater than 7 at 1 min and 9 or more at 5 min. None needed resuscitation. The pH of each solution was tested using a digital pH meter at the end of the procedure. The average pH of the alkalinized group was 7.20 (range 7.10-7.30); that of the control group was 4.91 (range 4.60-5.30) (P < 0.001).
Alkalinization of local anaesthetic solutions to speed up the onset of action has been used with varying degrees of success by several workers [18-20]. Another method to reduce the onset time has been the production of carbonated solution [21-23]. For example, lignocaine has been acidified by carbonation and is produced commercially by Astra Pharmaceuticals. Early work by Bromage indicated the superiority of such carbonated solutions compared with plain lignocaine in open studies in which a single local anaesthetic bolus was injected [22, 23]. Alkalinized solutions of 2 % lignocaine with adrenaline 1 in 400000 were compared with plain and carbonated lignocaine solutions for elective Caesarean section by Liepert and colleagues [21], who did not find any significant difference in the onset times (approximately 20 min) for all three groups. However, an incremental technique was used to deliver the local anaesthetic into the extradural space. We chose to use a bolus technique after a test dose had been given, as differences in onset times should be more apparent than with an incremental method. We found that the alkalinized mixture consistently had a more rapid onset of action which often reduced the waiting time to surgery by 50%. In addition, the extradural block was thought to be extremely dense in nature and provided good operating conditions without any patient experiencing pain or discomfort during the procedure. The onset times for the control mixture were comparable to those reported by Howell and colleagues [14]. Routine use of such a mixture has some disadvantages, including a potential for error in mixing four different drugs and unknown stability of the resultant solution. At present we mix the solutions immediately before use, as we have no data on the stability of this alkalinized mixture.
ACKNOWLEDGEMENTS We thank Dr R. Newcombe, Senior Lecturer in Medical Statistics, University Hospital of Wales for evaluating the data.
REFERENCES 1. Laishley RS, Morgan BM. A single dose epidural technique for Caesarean section. A comparison between 0.5% bupivacaine plain and 0.5% bupivacaine with adrenaline. Anaesthesia 1988; 43: 100-103. 2. Thorburn J, Moir D D . Epidural analgesia for elective Caesarean section technique and its assessment. Anaesthesia 1980; 35: 3-6. 3. Paech MJ, Westmore MD, Speirs HM. A double-blind comparison of epidural bupivacaine and bupivacaine/ fentanyl for Caesarean section. Anaesthesia and Intensive Care 1990; 18: 22-30. 4. Russell IFC. Spinal is better than epidural anaesthesia for elective Caesarean section. In: Morgan B, ed. Controversies in Obstetric Anaesthesia. Scvenoaks: Edward Arnold, 1990; 1-11. 5. Crawford JS, Davies P, Lewis M. Some aspects of epidural block provided for elective Caesarean section. Anaesthesia 1986; 41: 1039-1046. 6. Michie AR, Freeman RM, Dutton DA, Howie HB. Subarachnoid anaesthesia for elective Caesarean section. A comparison of two hyperbaric solution. Anaesthesia 1988; 43: 96-99. 7. Russell IF, Holmquist EL. Subarachnoid analgesia for Caesarean section. A double-blind comparison of plain and hyperbaric 0.5% bupivacaine. British Journal of Anaesthesia 1987; 59: 347-353. 8. Lesser P, Bembridge M, Lyons G, Macdonald R. An evaluation of a 30-gauge needle for spinal anaesthesia for Caesarean section. Anaesthesia 1990; 45: 767-768. 9. Cesarini M, Torrielli R, Lahave F, Mene JM, Cabiro C. Sprotte needle for intrathecal anaesthesia for Caesarean section: incidence of postdural puncture headache. Anaesthesia 1990; 45: 656-658. 10. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 1979; 51: 285-287. 11. Marx GF. Cardiotoxicity of local anesthetics. Anesthesiology 1984; 60: 3-5. 12. Abboud TK, Kim KC, Noueihed R, Kuhnert BR, Der Mardirossian N, Moumdjian J, Sarkis F, Nagappala S. Epidural bupivacaine, chlorprocaine or lidocaine for Cesarean section—maternal and neonatal effects. Anesthesia and Analgesia 1983; 62: 914-919.
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 22, 2015
DISCUSSION
However, alkalinized solutions of bupivacaine and adrenaline have been shown to be stable for up to 6h [24]. It has been suggested that sodium bicarbonate might be added to a premixed syringe of bupivacaine and lignocaine with adrenaline 1 in 200000 using an IMS (International Medication System) type of cartridge.
ALKALINIZED LOCAL ANAESTHETICS IN OBSTETRICS
19. Difazio CA, Carron H, Grosslight KR. Comparison of pH adjusted lidocaine solutions for epidural anesthesia. Anesthesia and Analgesia 1986; 65: 760-764. 20. Tackley RM, Coe AJ. Alkalinised bupivacaine and adrenaline for epidural Caesarean section. Anaesthesia 1988; 43: 1019-1021. 21. Liepert DJ, Mcmorland GH, Gambling DR, Kim HK, Ross PLE. Comparison of lidocaine CO,, 2 % lidocaine hydrochloride, and pH adjusted lidocaine hydrochloride for Caesarean section anaesthesia. Canadian Journal of Anaesthesia 1990; 37: 333-336. 22. Bromage PR. A comparison of the hydrochlonde and carbon dioxide salts of lidocaine and prilocaine in epidural analgesia. Ada Anaesthesiologica Scandinavica 1965; (Suppl. 16): 55-69. 23. Bromage PR. Improved conduction blockade in surgery and obstetrics: carbonated local anaesthetics. Canadian Medical Association Journal 1967; 97: 1377-1384. 24. Bonhomme L, Benhamau D, Martre H, Prcaux N. Chemical stability of bupivacaine and epinephrine in pH adjusted solutions. Anesthesiology 1987; 67: A279.
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on July 22, 2015
13. Paech MJ. Epidural anaesthesia for Caesarean section: a comparison of 0.5 % bupivacainc and 2 % lignocaine both with adrenaline. Anaesthesia ana" Intensive Care 1988; 16: 187-196. 14. Howell P, Davics W, Wrigley M, Tan P, Morgan B. Comparison of four local extradural anaesthetic solutions for elective Caesarean section. British Journal of Anaesthesia 1990; 65: 648-653. 15. Scott DB, Hibbard BM. Serious non-fatal complications associated with extradural block in obstetric practice. British Journal of Anaesthesia 1990; 64: 537-541. 16. Scow LT, Lips FG, Cousins MJ, Mather LE. Lidocainc and bupivacaine mixtures for epidural blockade. Anesthestology 1982; 56: 177-183. 17. De Jong RH, Bonin JD. Mixtures of local anesthetics are no more toxic than the parent drugs. Anesthesiology 1981; 54: 177-181. 18. McMorland GH, Douglas MJ, Jeffrey WK, Ross PLE, Axelson JE, Kim JHK, Gambling DR, Robertson K. Effect of pH adjusted bupivacaine on onset and duration of epidural analgesia in parturients. Canadian Journal of Anaesthesia 1986; 33: 537-541.
703