International Journal of Obstetric Anesthesia (2008) 17, 208–2110959-289X/$ - see front matter �c 2008 Elsevier Ltd. All rights reserved.

doi:10.1016/j.ijoa.2008.01.010

EDITORIAL

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Many recipes for the same dish: can minor modification cause

major improvement?

In this issue of the International Journal of ObstetricAnesthesia, a paper by Cesur and colleagues demon-strates a remarkable reduction in the incidence of hypo-tension (from 67% to 14%) with only a slight change intheir caesarean section spinal anaesthetic technique.1

Along with the reduction in hypotension the authorsnoted that the incidence of nausea fell from 53% to14% and mean ephedrine use from 20 mg to 2 mg.1

The only ‘prophylaxis,’ used in both groups, was theinfusion of crystalloid 10 mL/kg over 15 min beforethe spinal. However, based on our current understand-ing of factors governing the spread of hyperbaric andplain solutions of bupivacaine, the authors have beenunable to convince the editors and reviewers of theirunderlying hypothesis as to why sequential injection of1 mL of 0.5% plain bupivacaine followed by 1 mL of0.5% hyperbaric bupivacaine should work as postulated.Nevertheless, the editors, after much discussion of allpossible reasons for such extraordinary results and, wellaware of the many examples throughout medical historywhere established opinion rejected a new theory or pre-vented for many years the acceptance of a treatment ta-ken as read today, decided to publish the paper in full sothat you, the readers, can decide for yourself, or betterstill repeat the study.

The aim of the study was to investigate whether thesequential injection technique could eliminate some ofthe disadvantages of plain and hyperbaric bupivacainewhile, at the same time, preserving the advantages ofboth drugs. The authors’ hypothesis is that sequentialinjections of 1 mL plain and 1 mL hyperbaric bupiva-caine administered in the sitting position are the equiv-alent of two different low-dose drugs and theirbehaviour must be considered independently. Once thedrugs are injected and patients laid supine on a wedge,the authors claim that hyperbaric bupivacaine spreadsunder the influence of gravity to the upper thoracic der-matomes while plain bupivacaine, unaffected by gravity,remains in the lumbar and lower thoracic regions, rein-forcing anaesthesia in these lower dermatomes. Thisdrug distribution, they suggest, results in a concentra-tion gradient of bupivacaine throughout the spinal canaland the reduced incidence of hypotension observed is aconsequence of the low concentration of bupivacaine inthe upper part of the thoracic spinal canal being insuffi-cient to block sympathetic nervous system outflow.

The authors’ idea for their novel technique was basedon the premise described by Rawal et al. for combinedspinal-epidural (CSE): that limiting the dose of spinaldrug would lead to a dense block of lower spinal seg-ments, while the epidural could be used to extend theblock to upper thoracic segments and thus minimisehypotension.2 As regards their hypothesis for sequentialinjections of plain and hyperbaric bupivacaine, there aretwo problems. First, in order to restrict the block to thelower dermatomes, Rawal and colleagues used hyper-baric bupivacaine (mean dose 8.2 mg) injected in the sit-ting position. The technique did indeed restrict the blockas the spinal hyperbaric bupivacaine provided adequateanaesthesia for only 27% of patients. This is quite theopposite to the hypothesis under consideration, thatan even smaller dose of hyperbaric bupivacaine injectedin the sitting position will spread to the upper thoracicdermatomes. Secondly, in a subsequent study by thesame institution specifically investigating the incidenceof hypotension with the sequential CSE technique andusing 7.5 mg of spinal hyperbaric bupivacaine, therewas no difference in the incidence of hypotension oncethe epidural was used to extend the block to the upperthoracic dermatomes.3

Another difficulty for the sequential injection theoryis the abundant evidence that, even in pregnant women,plain bupivacaine is hypobaric,4 and as long as a patientremains in an upright position, plain bupivacaine ‘floats’upwards while hyperbaric bupivacaine sinks rapidly intothe sacral canal. This behaviour of anaesthetic agents isto be expected and many studies confirm this. Eventhose that more closely mimic the methodology anddoses used by Cesur and colleagues do not support theirhypothesis. In one study using sequential injections ofhypobaric fentanyl followed by either plain or hyper-baric bupivacaine, the authors observed that hypobaricagents ‘floated’ upwards while the hyperbaric agentwas confined to the lower thoracic and lumbar areas.5

However, in this study women remained reclining for30 minutes.5 In another study, comparing 1-mL dosesof plain and hyperbaric 0.25% bupivacaine (mixed withfentanyl 0.3 mL) injected while the patients were sittingand who were then laid in a supine wedged positionwithin 2–3 minutes, it was noted that the level of blockwas significantly higher in the plain bupivacaine group.6

A study of hyperbaric versus hypobaric sufentanil

Editorial 209

injected while patients were in the sitting position andwho were then laid lateral or supine after an epiduralcatheter had been secured, noted there was significantlypoorer analgesia in the hyperbaric sufentanil group.7

The authors postulated that this was because the initialsitting position encouraged rapid ascent of the hypo-baric solution to supraspinal sites in the brain stem!Finally, in a recent study, very low-dose 0.5% plainbupivacaine was compared with a conventional doseof 0.5% hyperbaric bupivacaine (4.5 mg plain v 12 mghyperbaric, both with fentanyl 50 lg and morphine200 lg). Injections were made with patients sittingfollowing which they were immediately laid supine ona wedge. The mean maximum level of block in bothgroups was C8 and there was no difference in the inci-dence of hypotension.8 All these data indicate that whenpregnant women receive spinal injections in the sittingposition and are then repositioned to a supine wedgedposition even small doses of hypobaric solutions, includ-ing plain bupivacaine, rapidly spread to the upper tho-racic region while small volumes of hyperbaricsolutions may suffer a restricted spread. However, thisdoes not necessarily detract from the authors’ basic pre-mise as there could still be a concentration gradient ofbupivacaine, but for a reason opposite to that proposed.With the technique as described,1 it would be plainbupivacaine that one would expect to spread to theupper thoracic region while hyperbaric bupivacainewould tend to be restricted to the lower thoracic andlumbo-sacral areas. Could this be the explanation forthe concentration gradient proposed by Cesur andcolleagues?

Several studies of plain and hyperbaric bupivacainefor caesarean section indicate that after the mother isplaced in a supine wedged position both drugs spreadto the same extent.9–12 The authors of the current studydismiss these results because the volumes/doses usedwere ‘‘large’’ (2-3.0 mL, 10-15 mg) and the drugs werenot given sequentially in small doses. One can acceptthis argument with regard to these studies,9–12 but it isnot so easy to dismiss data from another study indicat-ing no difference in the spread of low-dose plain orhyperbaric bupivacaine (6.6 mg) or the fact that it wasthe plain bupivacaine group that had the higher inci-dence of hypotension.13 However, it does need to bepointed out that in this latter study,13 the initial spinalinjections were made with the patients in the right lateralposition and so during spinal injection gravitational ef-fects on spread would be non existent and both groupswould be exposed to an identical effect from the massmovement of cerebrospinal fluid (CSF).

It seems that all evidence relating to spinal anaesthe-sia in women undergoing caesarean section demon-strates that various volumes/doses of hyperbaric andplain bupivacaine, when injected on their own, spreadin a similar manner and achieve the same block height

but, of course, none of the studies compared a sittinglow-dose sequential injection group. Since mass move-ment of CSF caused by placing a pregnant woman atterm in the supine wedged position is one of the predom-inant factors governing the spread of spinal agents, is itpossible that two drugs of different baricity, injected inclose sequence, would be affected to a different extent?If the small volume of hyperbaric bupivacaine rapidlyredistributed to the sacral region, then it is possible thatit could be less influenced by the mass movement of CSFas discussed above.6–8

One must always bear in mind some as yet unrecogn-ised factors that could result in a re-evaluation or are-interpretation of the facts. As an example of suchunknowns, Mike Tunstall used to encourage his traineesto have an open and enquiring mind as he told them thestory of the development of Entonox. Dr Tunstall wasadvised by some of the most experienced gas physicistsof the day that his proposal to mix nitrous oxide andoxygen in the same cylinder was a waste of time. It couldnot be done. Once under pressure, the nitrous oxidewould simply settle in liquid form at the bottom of a cyl-inder while all the oxygen remained in gaseous form atthe top. Dr Tunstall ignored the advice and the truth,as we know today, is very different!

A significant concentration gradient of bupivacaineas a result of the sequential injection technique seemsparamount for the theory as described to result in a par-tial blockade of the sympathetic nervous system, henceaccounting for the difference in the incidence of hypo-tension. The authors suggest that even with an adequatesurgical block into the upper thoracic dermatomes thedifferent concentration of bupivacaine may affect thesympathetic nervous system differently. Unfortunately,studies used to support this hypothesis do not seem todo so. I agree with the authors when they state ‘‘whiledifferent doses (of bupivacaine) produce similar segmen-tal levels, they do not (all) result in satisfactory analgesiaand a similar incidence of hypotension.’’ In making thisstatement the authors fail to appreciate that in the stud-ies referred to (1) the blocks were assessed by pinprick,(2) in the higher dose groups there was a significantlybetter quality of surgical analgesia and (3) associatedwith this there was a greater incidence of hypotensionin the higher dose groups. The fact that different dosesof spinal bupivacaine produce the same level of blockto pinprick but provide a very different quality of surgi-cal anaesthesia is well known and has been discussed indetail previously.14–16 In essence, pinprick testing doesnot identify different densities of block at a lower spinalcord level but these variations in block density are re-vealed by differences in efficacy: higher bupivacainedoses give more efficacious blocks and a greater degreeof hypotension.17–20 I am not aware of any study wherelower doses of bupivacaine, without adjuvant drugs,have provided a similar adequacy of surgical anaesthesia

210 Editorial

to higher doses, and also a lower incidence of hypoten-sion. A lower incidence of hypotension is always associ-ated with a less dense block and a poorer quality ofsurgical anaesthesia. This is quite different from thefindings of Cesur and colleagues. They observed no dif-ference in onset, spread, duration or surgical quality ofthe blocks in their two groups, yet one had a dramati-cally reduced incidence of hypotension.

Have Cesur and colleagues discovered a techniquethat, for some as yet unexplained reason, truly reducesthe incidence of hypotension without compromisingblock efficacy, or are the findings simply due to a type1 error? The possibility of a chance effect cannot be ig-nored. Other data presented are unusual and suggestchance effects. Out of 72 patients there were no casesof post dural puncture headache even though a 25-gaugeQuincke needle with the bevel facing cephalad was used.Previous studies suggest an expected headache rate inthe region of 15-22%.21–23 No intrathecal opioids wereused yet there were no cases requiring supplementaryanalgesia. Previous studies using 8–10 mg of unsupple-mented 0.5% hyperbaric bupivacaine for spinal anaes-thesia for caesarean section report a need foradditional intra-operative analgesia varying from 20–95% whether lateral or sitting positions were used forthe injection.19,24,25

Before accepting the results, remarkable as they are,the study needs to be repeated and, as well as observa-tions on the blood pressure, in order to clarify anyunderlying mechanism, there must be as much detailas possible about the onset, the extent, and the durationof the block to different sensory modalities (cold, sharp,touch). Additionally, to address some limitations of thecurrent study, a four-group study would be the ideal.This would compare injections made in the sitting posi-tion of (1) hyperbaric bupivacaine alone, (2) plainbupivacaine alone, (3) sequential injections of plain thenhyperbaric bupivacaine, (4) sequential injections ofhyperbaric and then plain bupivacaine.

The results as presented suggest that a simple modifi-cation to the basic technique of spinal anaesthesia hasthe potential to minimise hypotension without compro-mising anaesthetic efficacy. Were this to be so, it wouldrepresent a significant advance in the history of spinalanaesthesia for caesarean section, leading to yet furtherrefinements.

Ian RussellConsultant Anaesthetist & Honorary Senior Lecturer,

Department of Anaesthesia, Hull Royal Infirmary, Hull

UK

References

1. Cesur M, Alici H A, Erdem A F, Borekci B, Silbir F. Spinalanesthesia with sequential administration of plain and hyperbaric

bupivacaine provides satisfactory analgesia with hemodynamicstability in cesarean section. Int J Obstet Anesth 2008; 17: 217–22.

2. Rawal N, Schollin J, Wesstrom G. Epidural versus combinedspinal epidural block for cesarean section. Acta AnaesthesiolScand 1988; 32: 61–6.

3. Thorkn T, Holmstrom B, Rawal N, Schollin J, Lindeberg S,Skeppner G. Sequential combined spinal epidural block versusspinal block for cesarean section: Effects on maternal hypotensionand neurobehavioral function of the newborn. Anesth Analg 1994;78: 1087–92.

4. McLeod G A. Density of spinal anaesthetic solutions of bupiva-caine, levobupivacaine, and ropivacaine with and without dex-trose. Br J Anaesth 2004; 92: 547–51.

5. Teoh W H, Sia A T. Hyperbaric bupivacaine 2.5 mg prolongsanalgesia compared with plain bupivacaine when added tointrathecal fentanyl 25 microg in advanced labor. Anesth Analg2003; 97: 873–7.

6. Rofaeel A, Lilker S, Fallah S, Goldszmidt E, Carvalho J.Intrathecal plain vs hyperbaric bupivacaine for labouranalgesia: efficacy and side effects. Can J Anesth 2007; 54:15–20.

7. Ferouz F, Norris M C, Arkoosh V A, Leighton B L, Boxer L M,Corba R J. Baricity, needle direction, and intrathecal sufentanillabor analgesia. Anesthesiology 1997; 86: 592–8.

8. Bryson G L, MacNeil R, Jeyaraj L M, Rosaeg O P. Small dosespinal bupivacaine for cesarean delivery does not reduce hypoten-sion but accelerates motor recovery. Can J Anesth 2007; 54: 531–37.

9. Russell I F, Holmqvist E L O. Subarachnoid analgesia forcaesarean section: A double blind comparison of plain andhyperbaric 0.5% bupivacaine. Br J Anaesth 1987; 59: 347–53.

10. Richardson M G, Collins H V, Wissler R N. Intrathecal hypobaricversus hyperbaric bupivacaine with morphine for cesarean section.Anesth Analg 1998; 87: 336–40.

11. Sarvela P J, Halonen P M, Korttila K T. Comparison of 9 mg ofintrathecal plain and hyperbaric bupivacaine both with fentanylfor cesarean delivery. Anesth Analg 1999; 89: 1257–62.

12. Hallworth S P, Fernando R, Columb M O, Stocks G M. Theeffect of posture and baricity on the spread of intrathecalbupivacaine for elective cesarean delivery. Anesth Analg 2005;100: 1159–65.

13. Vercauteren M P, Coppejans H C. Small-dose hyperbaric versusplain bupivacaine during spinal anesthesia for cesarean section.Anesth Analg 1998; 86: 989–93.

14. Russell I F. Assessing the block for caesarean section. Int J Anesth2001; 10: 83–5.

15. Russell I F. At caesarean section under regional anaesthesia, it isessential to test sensory block with light touch before allowingsurgery to start. Int J Obstet Anesth 2006; 15: 294–7.

16. Russell I F. The futility of using sharp pin-prick (or cold) to assessspinal or epidural anesthesia for cesarean section. Reg Anesth PainMed 2001; 26: 385–6.

17. Pedersen H, Santos A C, Steinberg E S, Schapiro H M, Harmon TW, Finster M. Incidence of visceral pain during cesarean section:The effect of varying doses of spinal bupivacaine. Anesth Analg1989; 69: 46–9.

18. Ben-David B, Miller G, Gavriel R, Gurevitch A. Low-dosebupivacaine-fentanyl spinal anesthesia for cesarean delivery. RegAnesth Pain Med 2000; 25: 235–9.

19. Choi D H, Ahn H J, Kim M H. Bupivacaine-sparing effect offentanyl in spinal anesthesia for cesarean delivery. Reg AnesthPain Med. 2000; 25: 240–5.

20. Kiran S, Singal N K. A comparative study of three differentdoses of 0.5% hyperbaric bupivacaine for spinal anaesthesia inelective caesarean section. Int J Obstet Anesth 2002; 11: 185–9.

21. Mihic D N. Postspinal headache and relationship of needle bevelto longitudinal dural fibres. Reg Anesth 1985; 10: 76–81.

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22. Tarkkila P J, Heine H, Tervo R R. Comparison of Sprotte andQuincke needles with respect to post dural puncture headache andbackache. Reg Anesth 1992; 17: 283–7.

23. Imarengiaye C, Ekwere I. Postdural puncture headache: a cross-sectional study of incidence and severity in a new obstetricanaesthesia unit. Afr J Med Sci. 2006; 35: 47–51.

24. Santos A, Pedersen H, Finster M, Edstrom H. Hyperbaricbupivacaine for spinal anesthesia in cesarean section. AnesthAnalg 1984; 63: 1009–13.

25. Abouleish E, Rawal N, Fallon K, Hernandez D. Combinedintrathecal morphine and bupivacaine for cesarean section. AnesthAnalg. 1988; 67: 370–4.