798 q 2000 Blackwell Science Ltd

FORUM

Supraclavicular brachial plexus block as a sole anaesthetic

technique in children: an analysis of 200 cases

R. Pande,1 M. Pande,1 U. Bhadani,2 C. K. Pandey2 and A. Bhattacharya3

1 Associate Professor, 2 Assistant Professor and 3 Professor and Head of Department, Department of Anaesthesiology

and Critical Care, B P Koirala Institute of Health Sciences, Dharan, Nepal

Summary

Classical supraclavicular brachial plexus block was used as the sole anaesthetic technique in 200 children

aged between 5 and 12 years undergoing closed reduction of arm fractures. The local anaesthetic used

was lidocaine 1.5% with epinephrine. The block was graded as satisfactory if surgical manipulation

could be performed without discomfort and unsatisfactory if general anaesthesia had to be given. In

182 children, the procedure was carried out under the block alone, whereas the remaining 18 patients

required general anaesthesia. The mean (SD) time required for performing the block was 9.1 (3.7) min

and the mean (SD) time to sensory blockade was 8.3 (2.3) min. The mean duration of analgesia was

< 3.5 h. There were few complications, with no incidence of pneumothorax in any patient. The

acceptability of the block by the children and the parents was 72 and 85%, respectively. The classical

supraclavicular brachial plexus block was found to be acceptable, effective and with a good success rate.

Keywords Anaesthetic techniques: regional; brachial plexus. Surgery: orthopaedic. Anaesthesia: paediatric.

.................................................................................................

Correspondence to: Dr R. Pande

Accepted: 10 October 1999

Brachial plexus block is often used to provide anaesthesia for

closed reduction of fractures of the upper extremity [1].

Reports confirm that the supraclavicular approach is easy to

perform [2] and provides reliable anaesthesia of the upper

extremity with excellent muscular relaxation [3, 4]. However,

there do not appear to be any reports of the use of classical

supraclavicular block [5, 6] in children in the recent past.

In our institution, which is situated in the eastern hills of

Nepal, we encounter a large number of children with

supracondylar fractures of the upper extremity. Most of these

children sustain fractures as a result of falling from a height,

usually from trees. As they are treated on a day-care basis, we

designed a prospective study of the feasibility of using classical

supraclavicular brachial plexus block as the sole anaesthetic

technique. In this clinical study, we evaluated the accept-

ability, simplicity, safety and effectiveness of supraclavicular

block in young children with upper extremity trauma.

Methods

This prospective study was undertaken in 200 ASA

physical status I and II children aged between 5 and

12 years who were scheduled to undergo closed

reduction of upper extremity fractures on a day-care

basis. Approval of the hospital's ethics committee was

obtained as was informed consent from each patient

and his or her parents. The procedure was explained in

detail to the children and their parents, who were

present in the operating theatre during the insertion of

the block. All blocks were performed or supervised by

the authors. Patients with an open wound or with

possible infection at the site of injection, those with

associated multiple injuries and those requiring open

procedures were not studied. The children were kept

fasting for solids for 4 h and for clear liquids for 2 h

and were premedicated with oral diazepam

0.2 mg.kg21 1 h before the procedure. No other

sedation was given during the procedure.

Technique

Every attempt was made to obtain the cooperation of the

children by talking, explaining and providing comfort

both to the parents and the children. If appropriate, an

offer of sweets and cold drinks after the procedure was

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made. Facilities for resuscitation, monitoring of vital

functions and the provision of general anaesthesia were

available. An intravenous cannula was inserted after the

application of EMLA cream and a pulse oximeter was

applied to a finger. Each child was placed supine on an

operating table, with the head turned to the opposite side.

A folded towel was placed longitudinally between the

shoulder blades in line with the spine. An assistant gently

pushed the shoulder back towards the mattress and down

towards the feet. A skin weal was raised 1 cm above the

midpoint of the clavicle, lateral to the subclavian artery.

A 23 G, 2.5-cm hypodermic needle with a syringe

attached was introduced through the weal and was

directed downwards, backwards and medially until

contact was made with the first rib. No conscious effort

was made to elicit paraesthesiae. If paraesthesiae occurred,

the local anaesthetic was injected and these patients were

entered into the paraesthesia group. If no paraesthesiae

were produced, local anaesthetic was injected after

establishing contact with the first rib. These patients

comprised the no paraesthesia group. Subsequently, we

analysed the various parameters in these two groups to

discover whether paraesthesiae made any difference in

supraclavicular block in children. After a negative

aspiration, lidocaine 1.5% with epinephrine 1 : 200 000

in a dose of 6 mg.kg21 was injected.

Assessment

Patients were assessed for co-operation during the block,

time of onset of sensory and motor blockade, and the

duration of analgesia. The children were labelled as co-

operative when the block could be given without any

restraint and un-cooperative when gentle restraint had to

be used. The time from positioning of the patient to

injection of the local anaesthetic was taken as the time

taken to perform the block. The time taken to explain the

procedure and motivate the patient was not included in

this time. Sensory testing was performed in areas supplied

by radial, ulnar, median and musculocutaneous nerves.

Sensory loss was assessed using a needle, and the loss of

sensation to pinprick was taken as an indication of sensory

block, whereas inability to move the affected extremity

was taken as the criterion of motor block. The times to

onset of sensory and motor blockade were recorded.

The block was considered satisfactory if surgical

manipulation could be performed without pain. How-

ever, it was termed unsatisfactory when the patient did

not allow manipulation and general anaesthesia had to be

given. At the end of the procedure, the children were

observed in the recovery area. Sweets and cold drinks

were offered to the children who had not received a

general anaesthetic. A recovery nurse asked the children

and their parents about the block using a structured

questionnaire. They were also asked whether they would

accept the nerve block again for similar procedures, if the

need arose.

The patients were observed for complications, such as

pneumothorax and local haematoma formation. A

routine chest X-ray was not performed. The patients

were discharged using the criteria laid down for our unit

and those coming from distant locations were advised to

stay overnight in the rest area provided within the hospital

campus. The parents were instructed to report to an

Accident and Emergency department if any problem

occurred. The patients and their guardians were advised

to protect the affected extremity and to take oral

ibuprofen 6 mg.kg21 when pain was experienced. The

patients were examined the next morning when they

visited the hospital for a check X-ray of the arm and were

asked about the overall duration of analgesia. The

demographic data, time taken to perform the block,

onset and duration of sensory and motor block were

analysed using the Z-test. The acceptability and success

rate were analysed using the Chi-squared test. The

complications were analysed using the Chi-squared and

Fischer's exact test where applicable. A probability value

, 0.05 was taken to be significant.

Results

The mean ages and weights of the patients studied are

given in Table 1. The study population was predomi-

nantly male (78%). The fractures included closed (78%)

and minor open fractures (22%). All procedures were

simple closed reductions. Supracondylar fracture of the

Table 1 Age, weight, block characteristics and acceptability inchildren undergoing supraclavicular brachial plexus block.Values are mean (SD) or number [%].

Paraesthesiagroup(n � 110)

Noparaesthesiagroup(n � 90)

Age; years 9.8 (2.7) 9.6 (2.9)Weight; kg 18.5 (2.9) 18.3 (3.2)Successful blocks 100 [91%] 82 (91%)Time taken to perform block; min 9.1 (3.6) 9.1 (3.8)Time to onset of sensory block; min 8.3 (2.3) 8.2 (2.8)Time to onset of motor block; min 15.1 (5.0) 15.2 (4.6)Duration of analgesia; h 3.3 (1.8) 3.4 (1.2)Acceptable to children 72 [65%] 72 [80%]*Acceptable to parents 90 [82%] 80 [89%]

*Statistical difference between groups, p , 0.05.

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humerus (69%) and fracture of both radius and ulna (24%)

were the most common fractures in this series (Table 2).

One hundred and fifty children were easily convinced

about the benefits of the block, whereas the other 50

children had to be gently restrained during the procedure.

One hundred and ten children noted paraesthesiae,

whereas first rib contact was not associated with

paraesthesiae in 90 patients. Paraesthesiae were described

as a painful sensation by 90 children, the remaining 20

children describing the sensation as merely unpleasant.

In 182 (91%) children, analgesia was complete and the

procedure could be undertaken without any supplemen-

tation, whereas 18 (9%) patients required general

anaesthesia. The success rate was similar in both the

paraesthesia and no paraesthesia groups (Table 1). There

were no statistically significant differences in the time

taken to perform the block, the time to onset of sensory

and motor blocks or duration of analgesia between the

two groups.

The overall acceptability rates of the supraclavicular

block to the children and their parents were 72 and 85%,

respectively. The acceptability of the block was signifi-

cantly higher in patients who did not experience

paraesthesiae (Table 1). However, there was no statistical

difference between the two groups regarding the accept-

ability of the technique to parents.

Complications and side-effects were observed in 19

children (Table 3), but no incidence of pneumothorax

was observed in either group. Neurological complications

continuing after the offset of the blocks were not seen.

Discussion

The use of regional analgesic techniques as a sole method

of providing surgical anaesthesia is uncommon in

children. Difficulty in obtaining cooperation often

prevents the use of these techniques and regional blocks

are, therefore, usually combined with general anaesthesia.

Regional anaesthesia is ideal for surgical procedures of the

distal humerus, elbow and proximal forearm, and has been

used successfully in patients undergoing closed reduction

of arm fractures [7]. Supraclavicular block provides

anaesthesia of the entire upper extremity in a shorter

time than any other brachial plexus block [8, 9] and is also

recommended for procedures on the proximal arm. It

provides ideal operating conditions with good analgesia,

complete muscular relaxation and sympathetic blockade,

which may reduce postoperative vasospasm, pain and

oedema.

Because of its simplicity and efficacy, the supraclavicular

approach to the brachial plexus was once the most

popular technique, but in recent times it has fallen from

favour because of the fear of pneumothorax [10]. Even in

combination with general anaesthesia, classical supracla-

vicular brachial plexus block is rarely performed in

children. The technique is not mentioned in the standard

paediatric anaesthesia textbooks. We chose supraclavicular

brachial plexus block because of our familiarity with the

technique in adult patients. Close observation of the

technique in the Gurkha children coming to our

institution revealed that they were brave and would

accept the block quietly in the presence of their parents. It

was after this initial encouraging success that we decided

to undertake this study.

The majority of the children could be persuaded to

accept the block. Although no deliberate effort was made

to elicit paraesthesiae, it could not be avoided in the

majority of children, most of whom described the

paraesthesiae as a painful sensation. Techniques that

deliberately seek paraesthesiae may increase the success

rate of brachial plexus blocks [11], but are associated with

pain and may lead to a higher incidence of nerve injury.

Paraesthesiae did not make any significant difference in

the quality of block in this study, and the success rate, time

taken to perform the block and onset of sensory and

motor blockade were similar in the two groups of

children.

The overall success rate of the block in our study was

. 90%. This high success rate may be attributed to the

anatomical conformation of the brachial plexus, which

has a low volume as it passes over the first rib. The

Table 2 List of arm fractures in order of decreasing frequency.

Location Fracture

Distal humerus SupracondylarForearm Radius and ulnaDistal radius Epiphyseal injuriesDistal radius FractureForearm MonteggiaForearm GalleazziElbow DislocationsProximal humerus FractureProximal humerus Epiphyseal injuriesDistal humerus Lateral condylar

Table 3 Complications and side-effects in children undergoingsupraclavicular brachial plexus block.

Paraesthesiagroup(n � 110)

Noparaesthesia group(n � 90)

Pneumothorax 0 0Subclavian artery puncture 8 4Haematoma formation 0 0Horner's syndrome 6 1

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distribution of anaesthetic solution is confined to the

compact brachial plexus sheath and, having a limited

vascular surface area for drug absorption, results in an

effective block. The anatomic landmark of the first rib has

been used successfully in a similar study [12, 13].

The use of lidocaine 1.5% with adrenaline (epinephr-

ine) resulted in rapid sensory and motor block in our

study. Although higher doses of lidocaine have been used

safely for brachial plexus block without any toxic effects,

we did not exceed the recommended maximum dose,

mainly because of safety concerns in the paediatric

population.

The incidence of complications was low and was

similar in the two groups. There were no pneu-

mothoraces in our series, compared with the high

incidence (2±5%) reported in the literature [14]. In the

absence of any clinical evidence of pneumothorax,

routine chest X-rays were not taken as immediate X-

rays may be of little use because a small air leak may take

some time to result in a significant pneumothorax.

Many safe alternative approaches to supraclavicular

brachial plexus have been suggested [15±19] but they all

have drawbacks and we have limited experience with

some of these techniques. The axillary approach is

difficult to use in upper extremity trauma because of

pain and the relative immobility of the limb. The

interscalene technique of Winnie [20], although quite

effective, is associated with potentially severe adverse

effects [21±24]. The subclavian perivascular approach

[25, 26] requires considerable experience in children and

can result in complications such as pneumothorax,

undesirable nerve blocks and subclavian vessel puncture.

It has been claimed that the parascalene [27] approach is

easier, more reliable and relatively safe, but this

technique was not used in this study because of our

unfamiliarity with it.

Parental presence during induction of anaesthesia was

found to be very effective in relieving anxiety and in

minimising the need for premedication in preschool

children [28]. The presence of parents in the operating

theatre had a soothing effect on the children and helped in

the execution of the block. The involvement of parents

during the procedure might have been responsible for the

higher acceptance of the block by the children. The

occurrence of paraesthesiae during the block was

associated with a lower acceptance by the children as a

result of the pain and discomfort.

The classical technique of supraclavicular brachial

plexus block was found to have the advantages of being

easy to perform, requiring a single injection once the first

rib was contacted. The success rate was high with a low

complication rate. Occurrence of paraesthesiae did not

make any significant difference to the success of the block.

The technique was acceptable to both the children and

their parents.

References

1 Clayton ML, Turner DA. Upper arm block anesthesia in

children with fractures. Journal of the American Medical

Association 1959; 169: 99.

2 Brown DL, Cahill DR, Bridenbaugh LD. Supraclavicular

nerve block: anatomic analysis of a method to prevent

pneumothorax. Anesthesia and Analgesia 1993; 76: 530±4.

3 Small GA. Brachial plexus block anesthesia in children.

Journal of the American Medical Association 1951; 147: 1648±

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4 Bridenbaugh LD. The upper extremity: Somatic blockade.

In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in

Clinical Anaesthesia and Management of Pain. Philadelphia, PA:

JB Lippincott, 1988;387±416.

5 Kulenkampff D. Die Anasthesia des Plexus brachialis.

Zentralblatt Fur Chirurgie 1911; 38: 1337±40.

6 Winnie AP. Regional anesthesia. Surgical Clinics of North

America 1975; 55: 861±92.

7 Leak WD, Wichell SW. Regional anesthesia in paediatric

patients: review of clinical experience. Regional Anesthesia

1982; 7: 64.

8 Brown DL. Brachial plexus anesthesia: an analysis of options.

Yale Journal of Biology and Medicine 1993; 66: 415±31.

9 Lanz E, Theiss D, Jankovic D. The extent of blockade

following various techniques of brachial plexus block.

Anesthesia and Analgesia 1983; 62: 55±8.

10 Brand L, Papper EM. A comparison of supraclavicular and

axillary technique for brachial plexus blocks. Anesthesiology

1961; 22: 226±9.

11 Hickey R, Garland TA, Ramamurthy S. Subclavian

perivascular block: influence of location of parasthesia.

Anesthesia and Anagesia 1989; 68: 767±71.

12 Fung BK, Gislefoss AJ. Evaluation of supraclavicular brachial

plexus block in upper extremity surgery. Ma Tsui Hsueh Tsa

Chi 1993; 31: 87±90.

13 Korbon GA, Carron H, Lander J. First rib palpation: a safer,

easier technique for supraclavicular brachial plexus block.

Anesthesia and Analgesia 1989; 68: 682±5.

14 Farrar M, Scheybani M, Nolte H. Upper extremity block:

effectiveness and complications. Regional Anesthesia 1981; 6:

133±4.

15 Kapral S, Krafft P, Eibenburger K, Fitzgerald R, Gosch M,

Weinstabl C. Ultrasound guided supraclavicular approach for

regional anesthesia of the brachial plexus. Anesthesia and

Analgesia 1994; 78: 507±13.

16 Lin SY, Jiang CJ, Luu KC, et al. The application of pulse

oximeter for supraclavicular brachial block. Ma Tsui Hsueh

Tsa Chi 1990; 28: 43±8.

17 Yamano Y. Safe method of supraclavicular brachial plexus

anesthesia. Archives of Orthopedic and Trauma Surgery 1983;

102, 92±4.

18 Moorthy SS, Schmidt SI, Dierdorf SF, et al. A supraclavicular

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lateral paravascular approach for brachial plexus regional

anesthesia. Anesthesia and Analgesia 1991; 72: 241±4.

19 Pham Dang C, Gunst JP, Gouin F, et al. A novel

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Analgesia 1970; 49: 455±66.

21 Kayerker UM, Dick MM. Phrenic nerve paralysis following

interscalene brachial plexus block. Anesthesia and Analgesia

1983; 62: 536±7.

22 Bashein G, Robertson HT, Kennedy WF Jr. Persistent

phrenic nerve paresis following interscalene brachial plexus

block. Anesthesiology 1985; 63: 102±4.

23 Uremy WF, Talts KH, Sharrock NE, et al. One hundred

percent incidence of hemidiaphragmatic paresis associated

with interscalene brachial plexus anesthesia as diagnosed by

ultrasonography. Anesthesia and Analgesia 1991; 72: 498±507.

24 Fujimura N, Namba H, Tsundole K, et al. Effect of

hemidiaphragmatic paresis caused by interscalene brachial

plexus block on breathing pattern, chest wall mechanics, and

arterial blood gases. Anesthesia and Analgesia 1995; 81: 962±6.

25 Winnie AP, Collins VJ. The subclavian perivascular

technique of brachial plexus anesthesia. Anesthesiology

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26 Ortells Polo MA, Garcia Guiral M, Garcia Amigueti FJ,

Carral Olondris JN, Garcia Godino T, Aguiar Mojarro JA.

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27 Dalens B, Vanneuville G, Tanguy A. A new parascalene

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Anaesthetists' Society Journal 1983; 30: 286±9.

FORUM

Early release pattern of S100 protein as a marker of brain

damage after warm cardiopulmonary bypass

M. Shaaban Ali,1 M. Harmer,2 R. S. Vaughan,3 J. Dunne3 and I. P. Latto3

1 Research Fellow, 2 Professor of Anaesthetics and 3 Consultant Anaesthetist, Department of Anaesthetics and Intensive

Care Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK

Summary

Warm blood cardioplegia may be more beneficial to the heart than cold cardioplegia, but the

effects of warm cardiopulmonary bypass and warm blood cardioplegia on the brain are

controversial. S100 protein is an early marker of brain damage and has been detected after cold

cardiopulmonary bypass. We studied S100 concentrations in 20 patients undergoing coronary artery

bypass surgery before and after warm cardiopulmonary bypass (34±37 8C) using warm blood

cardioplegia (37 8C) for all patients. The peak level of S100 protein occurred immediately after

warm cardiopulmonary bypass, then decreased progressively until the last measurement at 4.5 h

after bypass. The peak level appears to be dependent upon the age of the patient, with the

following regression equation: y � 23.2 1 0.08x, where y is S100 protein concentration in

mg.l21 and x is patient age in years. Further studies are needed to investigate the clinical

significance of this early release pattern. Patient age should be taken into account when studying

S100 protein levels after cardiopulmonary bypass.

Keywords Complications: neurological. Surgery: cardiovascular. Protein: S100.

.................................................................................................

Correspondence to: Dr M. Shaaban Ali

Accepted: 17 January 2000

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S100 protein is an acidic calcium-binding protein found

in high concentrations in glial and Schwann cells. It exists

in various forms, including alpha and beta configurations.

The beta subunit is highly brain specific and is well

established as a marker of cerebral injury after cardiac

surgery with cold cardiopulmonary bypass (CPB) [1±5].

High levels of S100 protein have been recorded soon after

cold CPB in between 11 and 87% of patients who

recovered without overt neurological injury [1, 2]. The

peak level of S100 protein occurred immediately after

cold CPB and then decreased for 5 h after CPB [2, 5],

with high levels recurring in some patients between 15

and 48 h after surgery [2]. These recurring high levels of

S100 protein were associated with peri-operative cerebral

complications such as stroke, delayed awakening and

confusion [2].

The effect of warm CPB and warm blood cardioplegia

on the brain is still controversial [6, 7]. However, warm

blood cardioplegia has been reported as being more

beneficial to the heart than cold crystalloid or cold blood

cardioplegia [8±10]. The major advantages of blood as a

cardioplegic perfusate are related to its ability to transfer

oxygen to tissue, to buffer changes in pH and to provide

the appropriate osmotic environment for myocardial cells.

All these major characteristics attributable to blood are

optimal at normothermia and may be decreased, absent or

even deleterious as blood temperature is lowered, hence

the advantage of normothermic blood cardioplegia over cold

cardioplegia [9]. Normothermicblood cardioplegia not only

prevents additional damage caused by ischaemia, hypother-

mia and reperfusion, but also, when the myocardium is at rest

and provided with fundamental nutritional factors, allows

some degree of cellular repair during the operative period

[9]. Therefore, aortic cross-clamping time is no longer

equivalent to ischaemic time [8].

The aim of this preliminary study was to evaluate the

S100 protein release pattern after warm CPB (34±37 8C)

in patients undergoing coronary artery bypass surgery.

Methods

After obtaining local research ethics committee approval

and written informed consent, we studied 20 patients

undergoing coronary artery bypass grafting. Patients with

a pre-operative history of cerebral injury, a history of renal

impairment (serum creatinine . 120 mmol.l21) or a past

history of open heart surgery were not studied. All

patients were premedicated with temazepam 30±40 mg

given orally 60±90 min before surgery. Anaesthesia was

induced with etomidate 0.2±0.3 mg.kg21 and fentanyl

10±20 mg.kg21. Pancuronium 0.1 mg.kg21 was given to

facilitate tracheal intubation. The lungs were ventilated

mechanically with oxygen-enriched air, adjusted to

achieve an end-tidal partial pressure of carbon dioxide

of < 4.7 kPa. Anaesthesia was maintained with boluses of

Figure 1 Mean S100 protein concentrations before and after cardiopulmonary bypass (CPB). Error bars indicate SD. *p , 0.01,

²p , 0.001 compared with prebypass levels with the Wilcoxon signed ranks test.

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804 q 2000 Blackwell Science Ltd

fentanyl to a total dose of 50 mg.kg21 and isoflurane in

oxygen at an end-tidal concentration of 0.5±1.0%.

Cardiopulmonary bypass was established using a

membrane oxygenator and a roller pump with an arterial

line filter. Perfusion was nonpulsatile with a flow rate of

2.4 l.min21.m22 body surface area. A pH-stat carbon

dioxide management (temperature-corrected blood gas)

strategy was employed. Cardiopulmonary bypass tem-

perature was maintained at 34±37 8C and intermittent,

antegrade warm blood cardioplegia (37 8C) was adminis-

tered to all patients.

Blood samples for S100 protein analysis were taken

from the arterial line before CPB, directly after CPB, at

skin closure and at 2.5 h and 4.5 h after CPB. Analysis

was performed using the monoclonal two-site immuno-

radiometric assay (Sangtec 100: Sangtec Medical AB,

Bromma, Sweden). A value of 0.2 mg.l21 in serum is the

lower level of sensitivity of this assay. Levels in excess of

0.5 mg.l21 are considered to be pathological [3].

Statistical analysis

All results were analysed using SPSS version 7.5 for

Windows and are presented as mean (SD), unless stated

otherwise. Differences from baseline were assessed by the

Wilcoxon signed rank test. Linear regression analysis was

used to determine the dependence of S100 protein levels

after the end of CPB with age, CPB duration and

ischaemic time.

Results

The mean (range) age of the patients was 63.5 (45±73)

years. The mean (range) aortic cross-clamp time was 51.7

(24±80) min and mean CPB time was 98.5 (44±140) min.

Table 1 Simple regression analysis of S100 protein concentration (in mg.l21) after cardiopulmonary bypass on age

Regression Standard

95% Confidence interval for b

Variable coefficient (b) error t-value p-value Lower boundary Upper boundary

Constant 23.222 2.037 21.581 0.131 27.504 1.058Age; years 0.079 0.031 2.496 0.022 0.012 0.146

Figure 2 Scatter plot of S100 protein concentrations after cardiopulmonary bypass (CPB) against age, with the regression line and 95%

confidence intervals around the line.

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S100 protein increased significantly from undetectable

levels before CPB to reach its peak at the end of warm CPB.

Levels subsequently decreased progressively for 4.5 h after

CPB (Fig. 1). The numbers of patients with increased S100

protein concentration . 0.5 mg.l21 (the pathological limit)

were 17 of 20 (directly after CPB), 14 of 19 (at skin closure),

seven of 20 (at 2.5 h) and four of 20 (at 4.5 h). S100 protein

release was significantly dependent only on the age of the

patients (Table 1). The regression equation directly after

CPB was y � 23.2 1 0.08x, where y is the S100 protein

concentration inmg.l21 and x is patient age in years (Fig. 2).

This means that for every additional year of age in the age

range of the patients studied, the mean serum level of S100

protein concentration increases, on average, by 0.08 mg.l21,

although there are wide confidence limits (0.01±

0.15 mg.l21). In addition, the age of the patients accounted

for 26% of the variance between patient concentrations of

S100 protein at the end of CPB (Fig. 2). All patients made an

uneventful recovery from surgery.

Discussion

The peak levels of S100 protein occurred at the end of

warm CPB, then decreased progressively until 4.5 h after

bypass. As all the patients enjoyed an uneventful recovery,

the increase in S100 protein may be due to subclinical

brain injury [3], which, in turn, may be due to diffuse

microembolic cerebral injury [4] and increased perme-

ability of the blood±brain barrier [5]. Grocott et al. [4]

confirmed the association between increased levels of

S100 protein after CPB and the number of microemboli,

particularly those occurring during aortic cannulation.

The injury to the blood±brain barrier may be due to

brain oedema [11] and the systemic inflammatory

response caused by CPB [12]. Harris et al. [11] have

shown that patients on warm CPB had signs of brain

oedema detected by magnetic resonance imaging 1 h after

CPB, although none of the patients experienced any

neurological complications. Such oedema may be re-

garded as indicative of either cytotoxic reactions or

vasogenic disorders, both of which are known to

compromise the blood±brain barrier [13]. Svenmarker

et al. [14] found that the S100 protein concentration after

CPB was significantly lower in patients when heparin-

coated tubing was used during CPB than when it was not

used. They suggested that this decrease in S100 protein

levels may be due to reduced complement activation and

systemic inflammatory response associated with the use of

heparin-coated tubing during CPB [14].

In our study, no significant association was found

between the duration of CPB and S100 protein

concentration. This is in agreement with the studies of

Blomquist et al. [5] and Taggart et al. [15]. However, it is in

contrast to the findings of Westaby et al. [3]. This discrepancy

may be because Westaby et al. studied more patients (34

compared with 20 in our study) and encountered a wider

range of CPB times (14±181 min compared with 44±

140 min in our study). In addition, it may simply be due to

different CPB temperatures (32±34 8C compared with

34±37 8C in our study).

The increased levels of S100 occurring soon after CPB

that are related to age suggest potential cerebral vulner-

ability in older patients. Age is known to be a risk factor

for increased neurological injury after cardiac operations

[16] and is the most important predictor of stroke after

coronary artery bypass grafting surgery [17]. Interestingly,

increased age has been found to predispose to impaired

cognitive function after cardiac surgery [18, 19]. The

most likely explanation is the increasing prevalence of

arteriosclerosis with occult cerebrovascular disease, as well

as an increased risk of embolism from ascending aortic

plaques in older patients [20].

The clinical significance of this early release pattern

after warm CPB requires further investigation. In

addition, this study underlines the importance of taking

patient age into account when studying S100 protein

concentrations after CPB.

Acknowledgments

We thank Professor W. W. Mapleson for his helpful

statistical advice. They also thank the cardiothoracic

surgeons for their assistance: Mr E. G. Butchart, Mr E. N.

P. Kulatilake and Mr R. Haaverstad.

References

1 Johnsson P, Lundqvist C, Lindgren A, Ferencz I, Alling C,

Stahl, E. Cerebral complications after cardiac surgery assessed

by S-100 and NSE levels in blood. Journal of Cardiothoracic

and Vascular Anesthesia 1995; 9: 694±9.

2 JoÈnsson H, Johnsson P, Alling C, Westaby S, Blomquist S.

Significance of serum S100 release after coronary artery

bypass grafting. Annals of Thoracic Surgery 1998; 65: 1639±44.

3 Westaby S, Johnsson P, Parry AJ, et al. Serum S100 protein: a

potential marker for cerebral events during cardiopulmonary

bypass. Annals of Thoracic Surgery 1996; 61: 88±92.

4 Grocott HP, Croughwell ND, Amory DW, White WD,

Kirchner JL, Newman MF. Cerebral emboli and serum

S100B during cardiac operations. Annals of Thoracic Surgery

1998; 65: 1645±50.

5 Blomquist S, Johnsson P, Luhrs C, Malmkvist G, Solem JO,

Alling C, Stahl E. The appearance of S-100 protein in serum

during and immediately after cardiopulmonary bypass

surgery: a possible marker for cerebral injury. Journal of

Cardiothoracic and Vascular Anesthesia 1997; 11: 699±703.

6 Martin TD, Craver JM, Gott JP, Weintraub WS, Ramsay J,

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Mora, CT. Prospective randomised trial of retrograde warm

blood cardioplegia: myocardial protection and neurological

threat. Annals of Thoracic Surgery 1994; 57: 298±304.

7 The Warm Heart Investigators. Randomised trial of

normothermic versus hypothermic coronary bypass surgery.

Lancet 1994; 343: 559±63.

8 Youhana AY. Warm blood cardioplegia. British Heart Journal

1995; 73: 206±7.

9 Lightenstein SV, Dalati HE, Panos A, Slutsky AS. Long

cross-clamp time with warm heart surgery. Lancet 1989; i:

1443.

10 Caputo M, Ascione R, Angelini GD, Suleiman MS, Bryan

AJ. The end of the cold era: from intermittent cold to

intermittent warm blood cardioplegia. European Journal of

Cardiothoracic Surgery 1998; 14: 467±75.

11 Harris DNF, Oatridge A, Dob D, Smith PLC, Taylor KM,

Bydder GM. Cerebral swelling after normothermic cardi-

opulmonary bypass. Anesthesiology 1998; 88: 340±5.

12 Cremer J, Martin M, Redl H, et al. Systemic inflammatory

response syndrome after cardiac operations. Thoracic Surgery

1996; 61: 1714±20.

13 Rowland LP, Fink ME, Rubin L. Cerebrospinal fluid:

blood±brain barrier, brain edema, and hydrocephalus. In:

Kandel ER, Schw JH, Jessel TM, eds. Principles of Neural

Science. East Norwalk, CT: Prentice Hall, 1991;1050±60.

14 Svenmarker SS, SandstroÈn E, Karlsson T, et al. Clinical effects

of heparin coated surface in cardiopulmonary bypass.

European Journal of Cardiothoracic Surgery 1997; 11: 957±64.

15 Taggart DP, Mazel JW, Bhattacharya K, et al. Comparison of

serum S100 beta levels during coronary artery bypas grafting

and intracardiac operations. Annals of Thoracic Surgery 1997;

63: 492±6.

16 Heyer E, Delphinn E, Adams D. Cerebral dysfunction after

cardiac operations in elderly patients. Annals of Thoracic

Surgery 1995; 60: 1716±22.

17 Newman M, Wolman R, Kanchuger M, et al. Multicentre

preoperative stroke risk index for patients undergoing

coronary artery bypass surgery. Circulation 1996; 94 (Suppl.

2): 74±80.

18 Newman M, Karmer D, Croughwell N, et al. Differential

age effects of mean arterial pressure and rewarming on

cognitive dysfunction after cardiac surgery. Anesthesia and

Analgesia 1995 81: 236±42.

19 Newman MF, Croughwell ND, Blumenthal JA, et al. Effect

of aging on cerebral autoregulation during cardiopulmonary

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Circulation 1994; 90 (part 2): II-243±49.

20 Blauth CI, Cosgrove DM, Webb BW, et al. Atheroembolism

from the ascending aorta: an emerging problem in cardiac

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103: 1104±12.

FORUM

Caudal ropivacaine and ketamine for postoperative

analgesia in children

H. M. Lee1 and G. M. Sanders2

1 Medical Officer and 2 Senior Medical Officer, Department of Anaesthesiology, Intensive Care & Operating Services,

Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, New Territories, Hong Kong

Summary

In a prospective, randomised, double-blind clinical study, we studied 32 ASA grade I and II boys

aged 18 months to 12 years, scheduled for circumcision under general anaesthesia on an

outpatient basis. They were randomly allocated to one of two groups: those in the ropivacaine

group received caudal ropivacaine 0.2% 1 ml.kg21 for postoperative analgesia and those in the

ketamine/ropivacaine group received caudal ropivacaine 0.2% 1 ml.kg21 plus caudal ketamine

0.25 mg.kg21. Postoperative pain was assessed using a modified 10-cm visual analogue scale and

analgesia was administered if the pain score exceeded a value of 3. The median duration of

analgesia was significantly longer in the ketamine/ropivacaine group (12 h) than in the

ropivacaine group (3 h, p , 0.0001), and subjects in the ropivacaine group required significantly

more doses of postoperative analgesia than those in the ketamine/ropivacaine group (p , 0.0001).

There were no differences between the groups in the incidence of postoperative nausea,

Anaesthesia, 2000, 55, pages 798±810 Forum................................................................................................................................................................................................................................................

q 2000 Blackwell Science Ltd 807

vomiting, sedation, emergence delirium, nightmares, hallucinations, motor block and urinary

retention.

Keywords Surgery: paediatric. Anaesthesia: paediatric. Anaesthetics, local: ropivacaine. Anaesthetics,

intravenous: ketamine. Anaesthetic techniques: epidural; caudal. Analgesia: postoperative.

.................................................................................................

Correspondence to: Dr G. M. Sanders. Present address: Anaesthetic

Department, Medway Maritime Hospital, Windmill Road, Gillingham

ME7 5NY, UK

Accepted: 17 January 2000

Paediatric day-case surgery now forms a substantial part of

the paediatric anaesthetic workload. The reasons for this

are increased patient satisfaction and increased economic

efficiency [1]. A problem that is often ignored is the

provision of adequate postoperative analgesia once the

child gets home [2]. Caudal epidural block is routinely

used for postoperative analgesia in paediatric surgery

where the operative site is subumbilical [3], but a large

proportion of these patients requires additional post-

operative analgesia if local anaesthetic alone is used [4].

We designed this study to ascertain whether the addition

of ketamine to ropivacaine, when administered caudally,

would prolong the duration of postoperative analgesia in

boys undergoing circumcision.

Ropivacaine is a new amide local anaesthetic. It has the

advantage over bupivacaine of causing less motor

blockade [5, 6]. This means that it may be more suitable

for day-case anaesthesia when early ambulation is

required. Ropivacaine has been used successfully for

caudal epidural blockade in children [5±7].

Ketamine exerts its analgesic effects by binding to a

subset of glutamate receptors stimulated by the agonist N-

methyl d-aspartate (NMDA receptors). These NMDA

receptors are located throughout the central nervous

system, including the spinal cord. Ketamine has been

shown to produce profound analgesia at the spinal cord

level in animals [8, 9]. Ketamine has also been demon-

strated to improve analgesic efficacy when administered by

the lumbar epidural route [10, 11]. Ketamine, in

combination with bupivacaine, has been shown to prolong

the duration of postoperative analgesia when administered

caudally in children undergoing orchidopexy [12] and

inguinal herniotomy [13]. The optimal dose of ketamine

(0.25 mg.kg21) for caudal epidural use in children has also

been determined [14].

Methods

The local research ethics committee approved the study,

and written informed consent was obtained from a parent

for each child in the study. Thirty-two boys aged between

18 months and 12 years, all ASA grade I or II, scheduled

to undergo circumcision under general anaesthesia on an

outpatient basis, were recruited into the study. Children

for whom there was a contraindication to caudal block

were not studied. At the time of recruitment, parents

were instructed in the use of a standard 10-cm visual

analogue pain scale in order to assess the level of

postoperative pain and judge the timing of the first

analgesic dose. Parents were asked to estimate the level of

their child's pain, with a score of 0 indicating that the

child was in no pain at all, up to a score of 10 indicating

that the child was in the worst pain possible. The use of

this pain scale by parents has already been validated [15].

No premedication was given, but EMLA cream was

applied to the dorsa of both hands 1 h before surgery. An

intravenous cannula was sited and anaesthesia was induced

with propofol 3±4 mg.kg21 and fentanyl 1 mg.kg21. An

appropriately sized laryngeal mask airway was then

inserted and anaesthesia was maintained with an end-

tidal isoflurane concentration of 0.8% with 65% nitrous

oxide in oxygen. Spontaneous respiration with a

paediatric circle system was used. Monitoring consisted

of pulse oximetry, ECG, noninvasive blood pressure,

inspired oxygen concentration and end-tidal carbon

Ropivacaine Ketamine/ropivacaine p

Age; years 7.1 (2.7) 7.1 (2.5) 0.903Weight; kg 23.4 (7.6) 23.8 (8.4) 0.875Duration of operation; min 32 [20±45] 30 [20±50] 0.568

Table 1 Patient characteristics and length ofoperation. Values are mean (SD) or median[range].

Forum Anaesthesia, 2000, 55, pages 798±810................................................................................................................................................................................................................................................

808 q 2000 Blackwell Science Ltd

dioxide, isoflurane and nitrous oxide concentration

measurements.

Following induction, the children were randomly

allocated to one of two groups for caudal epidural

analgesia. Patients in the ropivacaine group (n � 16)

received ropivacaine 0.2% 1 ml.kg21 and those in the

ketamine/ropivacaine group (n � 16) received ropiva-

caine 0.2% 1 ml.kg21 plus ketamine 0.25 mg.kg21

(10 mg.ml21 concentration). For patients in the ropiva-

caine group, 0.025 ml.kg21 of normal saline was also

administered caudally as a substitute for the ketamine to

ensure that equivalent volumes were injected into both

groups. The caudal blocks were performed by the

anaesthetist allocated to the list using an aseptic technique

and a 23 G needle. This anaesthetist was not blinded to

the drugs used.

In case of caudal block failure, intravenous fentanyl

0.5 mg.kg21 and rectal diclofenac 1 mg.kg21 were

administered in the recovery room. Caudal block failure

was defined as the patient experiencing any pain

whatsoever at the operative site on recovery room arrival.

The surgical procedure was standardised for each

patient. The duration of the operation was noted (time

from skin preparation to dressing application). Anaesthetic

agents were discontinued when the dressing was applied

to the wound and the time to spontaneous eye opening

noted. The time to spontaneous leg movement was noted

as an estimate of motor block. Sedation was assessed

30 min after recovery room admission and 4 h after

surgery using a simple objective scoring system (eyes open

spontaneously � 1, eyes open in response to verbal

stimulation � 2, eyes open in response to physical

stimulation � 3, unresponsive � 4). A sedation score of

0, indicating that the child's eyes were already open, was

not allowed. The time to spontaneous eye opening, time

to spontaneous leg movement and sedation score were

assessed by a recovery room nurse who was blinded to the

drugs administered caudally. At any time before hospital

discharge, the presence of nausea, vomiting, emergence

delirium, nightmares or hallucinations was noted. The

time to first micturition was noted.

While still in hospital and once discharged home,

parents assessed their child's pain level using the modified

visual analogue pain score. The parents were blinded to

the drugs administered caudally. Pain was assessed on an

hourly basis until the first dose of analgesic was

administered (unless the child was asleep). They were

instructed to administer postoperative analgesia (oral

paracetamol 15 mg.kg21 4-hourly as required) when

the pain score reached a level of 4 and to note the time of

this first analgesic administration. They were also asked to

record the number of doses of paracetamol given in the

first 24 h after the surgery.

Statistical analysis was performed using Student's t-test for

unpaired parametric data, and the Mann±Whitney U-test

and Chi-squared test for nonparametric data. The Statview

for Windows version 4.5 computer program was used.

Differences were considered statistically significant at

p , 0.05. Power analysis using data from the study by Cook

et al. [16], specifically the duration of postoperative analgesia,

revealed that having 16 patients in each group would give a

power for the study . 0.95. Retrospective power analysis of

the data from this study, specifically the time to first analgesia,

confirmed a power for the study . 0.95.

Results

Demographic data and duration of operation were similar

in the two groups (Table 1). There were no failures of the

caudal epidural block.

Ropivacaine Ketamine/ropivacaine p

Time to first analgesia; h 3 [1±5] 12 [7±24] , 0.0001Doses of analgesia in first 24 h

after surgery; n

3 [1±5] 1 [0±2] , 0.0001

Table 2 Postoperative analgesia. Values aremedian [range].

Table 3 Recovery characteristics and com-plications. Values are mean (SD) or median[range].

Ropivacaine Ketamine/ropivacaine p

Time to spontaneous eye opening; min 13.9 (9.5) 13.3 (10.9) 0.851Sedation score at 30 min 1 [1] 1 [1] 1.0Sedation score at 4 h 1 [1] 1 [1] 1.0Time to micturition; h 4.5 (1.8) 3.6 (1.7) 0.167Time to spontaneous leg movement; min 13.3 (9.3) 11.3 (9.0) 0.553Postoperative vomiting; n 1 0 0.31

Anaesthesia, 2000, 55, pages 798±810 Forum................................................................................................................................................................................................................................................

q 2000 Blackwell Science Ltd 809

The duration of postoperative analgesia, as measured by

the time taken for the pain score to reach 4, was

significantly longer in ketamine/ropivacaine than in the

ropivacaine group (p , 0.0001). The number of doses of

paracetamol administered in the first 24 h after surgery

was significantly greater in the ropivacaine group than the

ketamine/ropivacaine group (p , 0.0001; Table 2).

There were no differences between the two groups in

the time to spontaneous eye opening, 30 min and 4 h

sedation scores, time to micturition and time to

spontaneous leg movement. No patient had his hospital

discharge delayed because of prolonged motor blockade.

One patient in the ropivacaine group and none in the

ketamine/ropivacaine group had postoperative vomiting

(Table 3). No patients experienced emergence delirium,

nightmares or hallucinations.

Discussion

We designed this study to ascertain whether the addition of

ketamine to ropivacaine, when administered caudally, would

prolong the duration of postoperative analgesia in boys being

circumcised. We have shown that ketamine prolongs post-

operative analgesia by 9 h. This finding supports work

performed by other groups, who demonstrated the effect

with caudal bupivacaine [12, 13, 16]. Our study has also

shown a significant decrease in the need for subsequent

postoperative analgesia when caudal ketamine is used.

Additional postoperative sedation did not occur when

caudal ketamine was used. The time to spontaneous eye

opening, 30 min sedation scores and 4 h sedation scores

were the same for both groups. No patients in the

ketamine/ropivacaine group experienced any emergence

delirium, hallucinations or nightmares. These complica-

tions of caudal ketamine have been reported when higher

doses (0.5±1 mg.kg21) have been used, but never with a

dose of 0.25 mg.kg21 [14].

The duration of motor block, as measured by the time

to spontaneous leg movement, was the same for both

groups. Caudal ropivacaine at a concentration of 0.2% did

not cause motor blockade in any patient by the time of

recovery room discharge (30 min after surgery), although

further assessment of motor block was not performed after

this. Hospital discharge was not delayed in any patient by

motor block. Previous work has demonstrated prolonged

motor block when caudal bupivacaine 0.25% is used in

children [12, 13], so the results of our study suggest that

the use of ropivacaine 0.2% is preferable for caudal

epidural use in children undergoing day-case surgery

when early ambulation is necessary.

It has been demonstrated that low concentration and

high volume of caudally administered ropivacaine result in

a differential block in children. This is because the A-delta

and C nerve fibres are of small diameter and the distance

between the nodes of Ranvier is short [7]. Ropivacaine

has a lower intrinsic toxicity than bupivacaine [17], so

when combined with the low dose on a mg.kg21 basis as

used for this study, safety margins are increased.

In conclusion, the addition of ketamine 0.25 mg.kg21

to ropivacaine 0.2% 1 ml.kg21, when administered

caudally in children, prolongs the duration of postoperative

analgesia. The need for subsequent postoperative analge-

sics is also reduced. The behavioural side-effects of

ketamine were not seen and motor block did not occur

after recovery room discharge. The combination of

ropivacaine 0.2% with ketamine is suitable for caudal

epidural blockade in paediatric day-case surgery.

Acknowledgments

We thank the members of the Department of Anaes-

thesiology, Intensive Care & Operating Services, and in

particular Dr P. P. Chen, for their advice and assistance.

Thanks are also due to the recovery room nursing staff for

their help with data collection.

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