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A randomised study comparing the extent of block produced by spinal column height and body weight-based formulae for paediatric caudal analgesia

Background and Aims: Height and weight-based formulae are used for calculation of dose of medications for caudal analgesia but these have not been compared. We compared spinal column height-based Spiegel and weight-based Takasaki and Armitage formulae for achieving maximum height of sensory neuraxial block after caudal epidural analgesia in paediatric patients. Methods: In this double-blind randomised study, children aged between 1 and 6 years and planned for infra-umbilical surgery were randomly allocated to receive caudal epidural block (targeting T10level block) with 0.25% bupivacaine, using a volume calculated by modified Spiegel formula (group I), Takasaki formula (group II), and Armitage formula (group III). The Institute ethics committee reviewed and approved the study protocol. The primary endpoint of the study was the difference in the number of spinal segments blocked as assessed by pinprick method. The secondary endpoint was the difference in volume of 0.25% bupivacaine used among the groups. The groups were compared using one-way ANOVA. Results: Seventy-five patients (25 in each group) completed the study as per protocol. The mean number of spinal segments blocked was significantly different among groups (P < 0.001) with patients in group I (13.8 ± 0.83) showing significantly lower number of spinal segments blocked as compared to that in group II (15.8 ± 1.06; P < 0.001), and group III (16.8 ± 1.28; P < 0.001). The mean volume of 0.25% bupivacaine used in group I was significantly lower (P < 0.001) than that in group II and group III. Conclusion: Dose calculation in caudal epidural analgesia as per spinal column height-based modified Spiegel formula was more precise than bodyweight-based Takasaki and Armitage formulae.


INTRODUCTION
Caudal epidural analgesia is a frequently performed regional anaesthetic technique in paediatric patients undergoing surgical procedures because of its long-standing familiarity, high success rate and good safety profile. [1][2][3][4][5][6] It is prudent to use the minimal effective dose of local anaesthetic solution for caudal epidural analgesia, that yields a predictable level of neuraxial blockade whilst avoiding an undesirable high level of blockade and providing a greater margin of safety in the event of inadvertent intravascular injection. A number of studies have attempted to derive formulae in order to determine an optimal volume of local anaesthetic required to achieve a anaesthetics in caudal epidural block. [13,14] It might not be practically feasible to consider all these factors while deriving these formulae.
Scientific literature does not reveal direct comparisons between different formulae and anaesthesiologists use formulae based on their personal judgment and experience. However, concerns about the actual level of blockade that would be achieved and inadvertent higher level of blockade always exist. [15] Therefore, we planned to compare the level of sensory neuraxial blockade achieved by a dose of 0.25% bupivacaine calculated using three commonly used formulae namely, spinal column height-based Spiegel formula (modified for T 10 blockade), body weight-based Takasaki formula, and body weight-based Armitage formula in paediatric patients undergoing infra-umbilical surgeries. [7,8,12] The primary endpoint of the study was the difference in the number of spinal segments blocked amongst the three groups. The secondary endpoint was the difference in volume of 0.25% bupivacaine used amongst the three groups.

METHODS
This study was conducted at a large tertiary care referral hospital. All children aged between 1 and 6 years and planned for an infra-umbilical surgery were eligible for enrolment. Patients with physical status >II as per the American Society of Anesthesiologists (ASA) physical status classification system, history of allergy or adverse effects with local or regional anaesthetic use, local infection, bleeding diathesis, spinal deformities, or neuropathies, those taking aspirin or any other anticoagulants, total dose of local anaesthetic exceeding 2.5 mg.kg -1 and children of unwilling parents were excluded from this study. The Institute ethics committee reviewed and approved the study protocol (HP/pp 1634/2010). After informed consent from parents or legal guardians, subjects were randomly allocated into three groups using computer-generated random allocation number. Allocation concealment was ensured by having the random group assignment enclosed in serially numbered, sealed opaque envelopes. The sealed envelope was opened by an anaesthesiologist not involved in the study. The patient and the investigator who assessed the level of segmental blockade were blinded to group allocation. Spinal height and weight were measured in all subjects. The subjects received caudal epidural block with 0.25% bupivacaine after the completion of surgery with dose calculated as per designated formula. In group I, spinal column height-based Spiegel formula was used (effective for twenty segments i.e., T 3 level block) [8] i.e., Volume for T3 block ml D (Where D is the distance from C 7 to sacral hiatus in cm). It was modified for T 10 level block i.e., for 13 spinal segments as follows: 13 / 20 2 Volume for T block ml = D X (Where 20 represents number of segments from S 5 -T 3 , and 13 represent the number of segments from S 5 -T 10 ). Group II patients received 0.25% bupivacaine calculated according to the body weight-based Takasaki formula (for T 10 level block) [7] i.e., (Where 0.078 and 0.17 are constants and 13 is number of spinal segments up to T 10 ). Group III patients received 0.25% bupivacaine according to body weight (in kg) based Armitage formula for lower thoracic level [12] i.e.,

Volume for T10 block (ml) =1 ml per kg body weight
All subjects were pre-medicated with 0.5 mg.kg -1 oral midazolam, 30 min before induction of anaesthesia. Continuous monitoring of oxygen saturation (SpO 2 ), lead-II electrocardiogram (ECG), heart rate (HR) and intermittent non-invasive monitoring every five min of mean arterial pressure (MAP) were done during the operative procedure and post-operatively in the post-anaesthesia care unit (PACU). General anaesthesia was induced with either halothane in oxygen or thiopentone 5 mg.kg -1 with fentany l 2 µg.kg -1 (depending upon the presence of intravenous cannula). Tracheal intubation was done under the effect of atracurium 0.5 mg.kg -1 , and anaesthesia was maintained with 60% nitrous oxide in oxygen and 0.5% halothane.
After the completion of surgery before extubation, caudal block was performed in left lateral position using a 25-gauge caudal needle (MEDEREN, 30 mm) under aseptic precautions and the calculated volume of 0.25% bupivacaine was administered. Neuromuscular blockade was reversed with neostigmine 0.05 mg.kg -1 and glycopyrrolate 0.01 mg.kg -1 after administration of caudal block. In the PACU, the level of sensory blockade and sedation score were assessed using pin-prick method and Ramsay sedation score, respectively, at 5, 10, 15, 20, 30, 60 and 120 min. In subjects ≤4 years, a positive response to pin prick was recorded when reflex movement along with wincing or cry and increase in heart rate to more than 10% of the baseline values were observed. In subjects >4 years, verbal response to pin prick were recorded. HR, SpO 2 and MAP were monitored at 5, 10, 15, 20, 25, 30, 45, 60, 75, 90, 105 and 120 min post-operatively. The children were transferred to the ward from PACU either after four segment regressions of sensory level or after two hours whichever was earlier, provided all other criteria for discharging from recovery room were also fulfilled. FLACC (face, legs, activity, cry and consolability) pain score was assessed prior to sensory blockade assessment. Caudal block was labelled as a failure whenever the FLACC pain score was >4 at 30 min post-operatively. [16] Post-operatively, intravenous paracetamol (15 mg.kg 1 ) was planned as rescue analgesic whenever FLACC pain score was >4. The duration of analgesia was defined as the time from administration of caudal block till the need of first rescue analgesic dose in the post-operative period. Haemodynamic compromise (fall in mean arterial pressure by more than 20% of baseline), motor weakness (modified Bromage score ≤4) or need of urinary catheterisation (assessed every 2 h based on clinical evidence of distension of urinary bladder or no passage of urine for 4 h after the procedure) were recorded as adverse events.
There are no studies comparing these formulae with each other. Assuming a type 1 error of 5%, power of 80%, effect size of 0.6 for number of spinal segments blocked between any two groups (out of three) and a standard deviation of 0.74, a sample size of 25 for each group was deemed sufficient to detect any significant difference between any two groups out of three. A further consideration for 20% drop outs gave the final sample size of 30 for each group. This meant a total sample size of 90 for the study. Data were analysed using statistical package for the social sciences (SPSS) software for windows, version 20.0 (IBM Corp., ARMONK, NY, USA). Continuous data were presented as mean with SD or median (with range) and categorical data were presented as frequencies.
The three groups were compared using one-way ANOVA. Post-hoc multiple comparisons between groups were done with Tukey test. All P values were two tailed and considered significant when <0.05.

RESULTS
Over a period of 36 months (from July 2010 to June 2013), 100 patients were screened for enrolment in this study [ Figure 1]. However, eight patients were ASA physical status >II, one patient had bleeding diathesis and parents of one patient refused consent. Ninety patients were enrolled as per the study protocol. Finally, 25 patients in each group completed the study protocol and were considered for statistical analysis. Rescue analgesic in the form of intravenous paracetamol was not required for any patient in any group during the study period. Patient characteristics are shown in Table 1. The three groups were comparable to each other with respect to age, sex, weight, spinal height, type of surgery and duration of surgery.
The sensory neuraxial blockade corresponding to T 10 was achieved in all patients except one in group I who had blockade till T 11 . In group I, the mean number of spinal segments blocked (13.8 ± 0.8) was significantly lower than that in group II (15.8 ± 1.1; P < 0.001) and group III (16.8 ± 1.3; P < 0.001). In group I, the mean volume used (8.7 ml ± 0.9) was significantly lower than that used in group II (11.1 ml ± 3.0; P = 0.001) and group III (13.1 ml ± 2.4; P < 0.001) [ Table 2]. The post-operative sedation score, duration of analgesia, modified Bromage score, MAP, HR and SpO 2 did not differ significantly amongst the three groups [ Table 3]. No events of hypotension or bradycardia requiring intervention were observed in any patient.

DISCUSSION
In our study, sensory level blockade corresponding to T 10 was uniformly achieved in all the three study groups. The volume calculated using weight-based Takasaki and Armitage formulae turned out to be higher and hence, consistently led to a higher level of neuraxial blockade (median blockade up to T 6 in Armitage and T 7 in Takasaki as compared to T 9 in Spiegel).
Various studies have shown that the injectate volume is a key determinant of the height of block and that the spread is higher when weight-based dosage administration is used in younger individuals. [17][18][19] In a study that investigated the spread of 1.5 ml/kg of 0.2% single shot ropivacaine using real-time ultrasound, the cranial spread was found to be inversely related to age, weight and height of the patient. [20] However, in a study by Thomas et al. where they compared different volumes (0.5, 0.75, and 1 ml.kg (-1) ) of local anaesthetic solutions containing radio-opaque contrast, a modest increase in spread of injectate with increasing volume was observed. The authors also noted that a volume of <1 ml/kg was unlikely to ascend to vertebral level higher than L 2 . [21] The use of the minimal yet adequate volume for achieving the sensory blockade of target dermatome is imperative to avoid complications associated with higher volumes such as local anaesthetic systemic toxicity (LAST), decreased cerebral flow and haemodynamic instability. Recently, Lundbald et al. observed a decline in mean cerebral blood flow (CBF) velocity and oxygenation after using higher volume (1.5 ml.kg -1 ) in caudal block in infants with unaffected systemic haemodynamic parameters   and advised caution while using higher volumes in patients with intracranial pathology. [22] Various radioisotope visualisation studies have demonstrated limited spread of local anaesthetics to the thoracolumbar junction. However, Lundbald et al. recognised the secondary cranial spread of local anaesthetic that, resulted in higher cutaneous median levels on testing at 15 min (T 4 ) compared to ultrasonographic assessment at 0 min (T 10 ) and after 15 min (T 8 ). [23] In our study, we used the pin-prick method for checking the cutaneous sensations at 5, 10, 15 and 30 min, therefore it is unlikely that this delayed cranial spread would be missed out in our observations.
In comparison to Spiegel and Takasaki formulae, calculation of local anaesthetic dose as per Armitage formula is simple, but it does not take into account height of the patient. Despite the widespread use of this formula, the studies grossly express the level of neuraxial blockade as high thoracic, mid thoracic and sacral without any objective account of specific spinal segments or their number. Similarly, in a large number of studies, caudal epidural block was administered pre-operatively and its efficacy and level of neuraxial blockade was assessed intra-operatively under the effect of either sedation or general anaesthesia, by observing indirect parameters such as heart rate and blood pressure that lack objectivity. [7][8][9]11,12] In the light of newer observations of reduced CBF and LAST with larger volumes of local anaesthetic, use of the precise and smaller volumes of local anaesthetic appears more prudent. [22] Our study shows that the height of spinal segments (column) might be more significant than the body weight, which often varies grossly even among children with same height.
If we generalise the mean volume used, the segments above T 9 appear to accommodate a larger volume per segment from T 9 to T 7 (1.2ml per segment) and 2.0 ml per segment from T 7 to T 6 . We did not use any objective method such as imaging or ultrasound to view the spread of local anaesthetic solution. Though it is difficult to explain this higher volume required to block the T 9 -T 6 segments, the studies involving imaging and epiduroscopy suggest that mid-thoracic segments tend to accommodate larger volumes compared to upper or lower thoracic spinal segments. [14,24] These observations perhaps may explain this relatively higher volume requirement per segment.
Use of a smaller volume is often considered a compromise of longer duration of analgesia. Silvani et al. compared the post-operative duration of analgesia and motor blockade using low volume high concentration (ropivacaine 0.375% at 0.5 ml.kg -1 ) with high volume low concentration (ropivacaine 0.1% at 1.8 ml.kg -1 ) in caudal blockade and observed that the ''high volume, low concentration'' regimen produced prolonged analgesia and lesser motor block compared to the ''low volume, high concentration'' regimen. [25] The difference of volume (0.5 ml vs 1.8ml.kg -1 ) is greater compared to our study (0.65 ml to 1.0 ml.kg -1 ). Since our patients underwent different surgical procedures involving dermatomal levels from lower thoracic (cystolithotomy) to sacral (club foot surgery), comparison of the duration of analgesia would not have been rational.
None of the patients in any group experienced haemodynamic compromise, motor weakness or needed urinary catheterisation in the post-operative period. Modified Spiegel and Takasaki formulae consistently yielded lower local anaesthetic volume for T 10 block as compared to Armitage formula. The relatively small number of patients and homogeneous population are important limitations of this study.

CONCLUSION
Our results show that dose calculation as per spinal column height-based modified Spiegel formula was more precise than body weight-based Takasaki and Armitage formulae for calculation of the volume of 0.25% bupivacaine for achieving T 10 blockade in caudal epidural analgesia for post-operative pain relief in paediatric population undergoing infra-umbilical surgeries.
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