Cerebral palsy (CP) is a heterogeneous group of nonprogressive permanent diseases of posture and movement control.1,2 In preterm and full-term newborns alike, it is associated with several prenatal, perinatal and postnatal factors, such as preeclampsia and intrauterine growth restriction, preterm birth, low birth weight, infection/inflammation, multiple pregnancy, other complications of pregnancy, respiratory distress and genetic disorders.2–5 The prevalence of CP ranges between 2 and 2.5 cases per 1000 live births2,6 and its incidence may be increasing due to improvements in obstetric and neonatal care.4,7 Different classifications of CP have been proposed based on the location and clinical manifestations of the brain lesions.8–11 Thus, CP may be classified according to a topographical approach or a physiological approach.12

Approximately 80% of children with CP will present with spasticity as the main motor impairment.12 Spasticity can be defined as velocity-dependent hypertonia associated with an increased myotatic reflex and is part of upper motor neuron syndrome.13

One of the most common methods used to assess CP in children is the expanded and revised Gross Motor Function Classification System (GMFCS).14,15

Due to the heterogeneous nature of CP, each patient needs to be managed with an individualised approach. Among the various nonsurgical treatment options, the use of botulinum toxin type A (BoNTA) is recommended in standard clinical practice (level A recommendation).5,16–18 Injection of BoNTA has been recommended as a therapeutic option in the treatment of dynamic equinovarus foot in children with CP, for whom no other conservative treatment has proven more effective (Level A recommendation).16

The efficacy and safety of the use of BoNTA for management of spasticity in the upper extremities in children with CP have been established in previous studies.19,20 In these patients, the use of BoNTA must be combined with occupational therapy programmes (strong recommendation, green light intervention).18 Several studies have demonstrated the efficacy of BoNTA in the treatment of spasticity in the lower extremities, with improvements in deformity and gait.21–23

From the perspective of specific goals, BoNTA is used for a broad range of indications, such as facilitating stretches in physical therapy and management of pain associated with spasms, including postoperative pain.24

Two main aspects must be taken into account when administering BoNTA to children: the technique to guide the injection and the sedation and analgesia strategy. Several techniques are available to guide the injection, including palpation, ultrasound, electromyography (EMG) or electrical stimulation.24

The selection of an adequate sedation and analgesia protocol (SAP) is necessary to reduce pain and anxiety in children that receive intramuscular BoNTA injections.

There is evidence of the efficacy and adequate tolerability of inhalation of a mix of oxygen and nitrous oxide for sedation and analgesia during intramuscular injection of BoNTA in children.25 However, an analgesia protocol consisting of nitrous oxide and anaesthetic cream was only effective in 50% of children.26

The development of a standard procedural SAP could help reduce pain and eliminate the anxiety resulting from these injections.

The aim of our study was to assess the impact of the sedation and analgesia strategy in the pain experienced by the patient.

We conducted a cross-sectional study in patients with CP managed in the Paediatric Rehabilitation Unit of the Hospital Materno Infantil in the city of Malaga, which we included by consecutive sampling according to the established inclusion and exclusion criteria, that were treated with BoNTA between November 2015 and June 2016.

The study protocol was approved by the Ethics Committee of the hospital. The parents of every participant received detailed information about the characteristics of the study and gave their consent in writing. We conducted the study in adherence with the ethical principles established in the Declaration of Helsinki and with good clinical practice guidelines.

The inclusion criteria were the following: children/adolescent aged 2–16 years, scheduled to receive BoNTA injections for treatment of spasticity. We excluded patients if they had any contraindication for treatment with BoNTA (history of allergic reaction, neuromuscular junction disorder, peripheral neuropathy, etc.), a coagulation disorder, could not tolerate sedation or were unwilling to comply with the protocol or the directions given by the researcher.

Assessment of painPatients aged less than 3 years

A trained observer assessed pain by means of the Face, Legs, Activity, Cry, Consolability (FLACC), a validated instrument with a possible score ranging from 0 to 10. It is based on the observation of facial expressions, leg movements, the level of activity, crying and ability to be soothed. Higher scores are indicative of higher levels of discomfort.28

Patients aged 3–7 years

We assessed pain by means of the Wong-Baker FACES pain rating scale (WBS), one of the existing faces scales that has been proven useful in multiple paediatric settings for assessment of pain.29 Patients were instructed to circle the face that best represented their level of pain. After this, we asked patients to rate their pain on a visual analogue scale (VAS) measuring 100mm with a horizontal orientation whose extremes were marked as “no pain” and “worst imaginable pain”.

Patients aged 8 or more years

We used a visual numerical scale developed by Walco and Howite with which pain is assessed as follows: 0, no pain; 1–2, mild pain; 3–6, moderate pain, 7–8, severe pain grave and 9–10, the most pain I’ve ever felt.

Fig. 1 shows the results of the MAS, numerical Walco and Howite pain scale, WBS and FLACC scale.

Figure 1.

Results of the modified Ashworth scale, numerical pain scale of Walco and Howite, Wong-Baker FACES scale and FLACC scale. FLACC, Face, Legs, Activity, Crying and Consolability. Modified Ashworth scale: Subjective scale that rates the severity of spasticity from 0 to 4, of proven reliability in adults (in its modified version) for assessment of spasticity in the elbow flexors and plantar flexors. Values: 0 No increase in muscle tone. 1 Slight increase in muscle tone, manifested by minimal resistance in part of the joint range of motion. 1+ Presence of a catch at some point in the range of motion. 2 More marked increase in muscle tone through most of the range of motion. 3 Considerable increase in muscle tone, passive movement difficult. 4 Rigid muscle contraction.

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A total of 124 patients met the inclusion criteria in absence of exclusion criteria: 32 (Group I); 33 (Group II); 29 (Group III) and 30 (Group IV).

Table 1 presents the main demographic and clinical characteristics of the sample.

The number of injections ranged between 2 and 14 and the number of injected muscles between 1 and 7.

Of the 124 participants, 56 (45.2%) had a level of pain equal to or less than 2 (Table 2).

A significantly greater proportion of patients had a pain score of 2 or less in Group III (intravenous deep sedation under the supervision of an anaesthesiologist) compared to all other groups under study (P<.001) (Fig. 2).

Figure 2.

Proportion of patients in each group under study that experienced a level of pain of 2 or less based on the pain scale scores. † P=.005 in comparison with the group under study. †† P=.01 in comparison with Group I and .001 in comparison with Group IV. * P<.001 in comparison with all groups under study.

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The injection of BoNTA was guided by ultrasound in 109 patients (87.9%) and by anatomical localisation in 15 (12.1%). Since manual injection based on anatomical landmarks was only used in Group I, we compared the level of pain within this group in patients that received ultrasound-guided BoNTA injections versus patients that received injections with insertion based on anatomical landmarks. The mean pain score was 3.36 (SD, 0.76) in patients in whom needle insertion was guided by anatomical landmarks and 5.19 (0.76) in patients in which it was guided by ultrasound (P=.1193).

Pain during administration of BoNTA was significantly lesser in children that received intravenous deep sedation under the supervision of an anaesthesiologist compared to children managed with other sedation strategies (Tables 3 and 4).

When it came to parental satisfaction, the proportion of parents that “strongly agreed” or “agreed” with the item “I think that the level of cooperation of my child was adequate” ranged between 70% in Group IV and 100% in Group III (P=.076) (Table 5). However, we found statistically significant differences in the other items (Table 5).

The proportion of physicians that “agreed” or “strongly agreed” with the statement “The cooperation of the patient allowed me to perform the intervention” ranged between 70% for Group IV and 100 for Group V (Table 5).

Table 6 presents the correlation between the level of pain and some of the variables under study. Pain was significantly correlated to age (r=−0.21; P=.0299) (Table 6).

The results of our study show that the choice of sedation and analgesia protocol has a significant impact in the level of pain experienced by patients with CP treated with BoNTA.

Although the response to children to stressful or painful situations differs substantially between individuals,30 there is evidence in the literature that inadequate pain management in children has a negative impact on future experiences involving painful processes.25,31 The recollection of a painful medical procedure can reduce the effect of pain medication in subsequent procedures31; thus, one study found that the memory of a painful dental procedure in the past was a predictor for reported pain in a subsequent dental procedure.32

In children that require repeated painful procedures, the pain experienced during the initial procedure has a significant influence on pain and anxiety scores in subsequent procedures.33

Comparing the results of our study with those of other authors poses challenges.

Brochard et al.26 found pain above 9 points in the CHEOPS scale in 38% of children that received injections while sedated with nitrous oxide and EMLA cream, who required a higher level of analgesia to perform the procedure. In our study, nitrous oxide was fairly effective in reducing pain in children with CP treated with BoNTA injections.

The results of this study are consistent with the findings of Gambart et al.,34 who assessed pain in children managed with nitrous oxide and an eutectic mixture of lidocaine and prilocaine (EMLA cream) and concluded that the anaesthesia protocol was inadequate in 1 out of 2 children (50%), with a greater level of pain in children receiving more than 8 injections.

Although treatment with BoNTA is effective and generally well tolerated,35 parents may worry about the pain associated with the procedure.36 In fact, the pain caused by injection has been reported as a reason for abandoning treatment with BoNTA in children.37

In our study, the level of pain differed significantly based on the selected SAP.

The proportion of parents that considered that the procedure was stressful to their children was low in Groups I and III and relatively low in the remaining 2 groups. These findings suggest that selection of the appropriate SAP significantly increases parental satisfaction with the procedure.

Although the comfort of the patient is important, it must be weighed against the risks posed to the patient. Children with CP may be at increased risk of complications of general anaesthesia,38,39 although we did not observe any adverse effects in any of the groups under study.

While the proportion of patients with a level of pain of 2 or less was significantly greater in the general anaesthesia group, this approach cannot be recommended for all patients. In addition, performance of anaesthetic procedures in patients with special needs may be challenging, while assessment of acute pain is complicated in children with significant cognitive impairments.27,34,39

The cooperation of the patient allowed performance of the intervention in most patients in all groups under study. This further corroborates the crucial importance of selecting an appropriate SAP.

We did not find significant differences in pain based on whether needle insertion was guided by ultrasound or based on anatomical landmarks. However, we ought to note that we did not originally design the study to assess the impact of insertion technique on the pain experienced by the patient. Our study had a power of 40% to detect a mean difference in pain of 1.8 points with a level of significance of 0.05.

Authors of previous studies have indicated the importance of using ultrasound to guide injection of BoNTA in different muscles.23,24,40 However, these studies were focused on the effectiveness of BoNTA rather than the pain experienced during the procedure.

Lastly, the only variable under study included in the model that was significantly associated with pain was age. This may be related to the fact that cooperative patients were assigned to Group I (topical anaesthetic), while patients that had been uncooperative in previous injections were assigned to the general anaesthesia group. Furthermore, patients in Group III were older compared to patients in Group II.

The results of our study demonstrate the importance of selecting an adequate sedation and analgesia protocol to reduce the stress associated with BoNTA injections in children with CP.

We received funding from Allergan Ltd. to support the writing of the manuscript.

The authors have no conflicts of interest to declare.