Infraorbital nerve block for postoperative pain following cleft lip repair in children

  • Protocol
  • Intervention



This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effects of infraorbital nerve block for postoperative pain following cleft lip repair in children.


Description of the condition

Postoperative pain is a barrier to quality of paediatric care and the proper management of this experience is a challenge. Acute pain often leads to adverse functional and organic consequences that may compromise surgical outcome. During the postoperative period, acute pain can also lead to psychological, cardiorespiratory and metabolic repercussions (Helgadóttir 2000). The cleft lip is one of the most common craniofacial birth defects and requires surgical correction in early ages (Arosarena 2007).

The connective tissue and skeleton of the face form during the third week of embryonic life by the migration of neural crest cells. Cleft lip is caused by failure in the fusion of the frontonasal and maxillary processes which takes place between the fourth and eighth weeks of embryonic development (Shkokani 2013). The abnormal sequence of lip development can lead to abnormal positioning of the tongue and affect palatal development. Although often associated, cleft lip and palate are different malformations, both embryologically and etiologically. Cleft lip may be part of a genetic syndrome or associated with other birth defects (Sykes 2005). Orofacial clefting is estimated to affect one in 500 to 700 live births. It is more frequent in Asians and Native Americans and in boys (60% to 80%) (WHO 2004). Cleft lip is associated with cleft palate in 68% to 86% of cases (Arosarena 2007).

In 70% of the cases, cleft lip and palate are not associated with genetic syndromes. Genetic predisposition, environmental factors and teratogenic agents (e.g. maternal smoking, zinc and folate deficiency, alcohol, pesticides, chemical solvents, antiepileptic drugs, etc.) have been investigated as potential causes or risk factors for orofacial clefts (Mossey 2009). It is possible to identify cleft lip on prenatal ultrasounds, starting at approximately 18 weeks' gestation, although sensitivity is still low, especially on two-dimensional ultrasound. In cases of suspected cleft lip on ultrasound, the patient should be seen by maternal-foetal specialists, and genetic counselling is recommended (Gagnon 2009).

The varied morphology of facial clefts, which may involve four different structures (the upper lip, alveolar process, hard and soft palate) and the possibility of unilateral or bilateral, complete or incomplete involvement, are challenges to the creation of a single classification (Rodriguez 2001). Regardless of the extension of the clefts, early surgical repair must be planned to minimise physical, psychological and social consequences. Affected individuals may have feeding and speech problems, in addition to increased risks of middle ear infections. The condition is associated with increased mortality from many causes and the aesthetic defect may cause social rejection and decreased quality of life (Law 2002; Shkokani 2013).

Surgical correction of cleft lip can be performed during the neonatal period or later. The ideal period for surgery depends on the severity of the deformity, the child's health and other factors that may influence the efficacy and safety of the procedure (Shkokani 2013). There is a consensus that the correction should be carried out as early as possible and it is often performed between the third and sixth months of life (Delgado 2005; Sykes 2005). The management of cleft lip involves a multi-disciplinary team to ensure comprehensive care including functional and aesthetic issues. There are several different treatment plans for the surgical correction of the deformity (Mathes 2006).

As expected after a surgical intervention in such a sensitive and delicate area, the immediate postoperative period of cleft lip repair may be associated with moderate to severe pain (Augsornwan 2008; Biazon 2008). This pain will require adequate analgesia to prevent the child from becoming agitated and touching the surgical site. This behaviour could disrupt the process of wound healing and compromise the aesthetic results as well as extend the time of hospitalisation.

Description of the intervention

Treatment of acute postoperative pain usually involves the use of non-steroidal anti-inflammatory drugs (NSAIDs), analgesics and oral or intravenous opioids, which may be associated with adverse effects such as nausea and vomiting, drowsiness and respiratory depression. These treatments are frequently underutilised in children due to safety concerns and lack of experience in pain management (Jonnavithula 2007). Another option to control postoperative pain is the injection of local anaesthesia into the surgical incision, but the procedure may distort the margins of the cleft and interfere with the aesthetic repair (Prabhu 1999). In the last two decades there has been a growing interest in regional anaesthesia for paediatric surgical procedures. Several techniques have been evaluated and tested in several types of paediatric surgery, including cleft lip repair (Gaonkar 2004; Jonnavithula 2007; Simion 2008; Takmaz 2009).

Infraorbital nerve block associated with general anaesthesia has been used to reduce postoperative pain after cleft lip repair. The infraorbital nerve is the terminal branch of the second division of the trigeminal nerve which differentiates into the infraorbital nerve after entering the ocular area through the inferior orbital fissure. It emerges through the infraorbital foramen dividing into four branches (inferior palpebral, external nasal, internal nasal, and superior labial), innervating the skin of the upper cheek, the mucous membrane of the maxillary sinus, the incisor, canine and premolar teeth, upper gums, skin and conjunctiva of the lower eyelid, part of the nose, skin and mucosa of the upper lip (Simion 2008).

How the intervention might work

Infraorbital nerve block is performed by injecting an anaesthetic in the infraorbital foramen, either intra- or extraorally (percutaneous). In the percutaneous approach, the infraorbital foramen is identified as a point halfway between the midpoint of palpebral fissure and the angle of the mouth, approximately 7.5 mm from the alar base; then a needle is introduced perpendicular to the skin and advanced until bone resistance is felt. The needle is then withdrawn slightly and after a negative aspiration test for blood, the local anaesthetic is injected (Bosenberg 1995; Takmaz 2009). For intraoral infraorbital nerve block, a finger marks the approximate point of the infraorbital foramen externally, as described above, then the lip is everted and the needle is inserted into the mucobuccal fold above the second premolar toward the infraorbital foramen (Jonnavithula 2007). The injected anaesthetic blocks the generation and propagation of impulses in excitable tissues by blocking sodium channels in the cell receptors. The absence of this ion prevents the transmission of pain sensitivity. This results in effective regional blockage of pain when these drugs are deposited near peripheral nerves, nerve roots, or the spinal cord. The effect of this process will depend on the dose, concentration and type of anaesthetic used (Strichattz 1976).

Why it is important to do this review

There are several procedures to control acute postoperative pain associated with cleft lip repair to ensure the comfort of the child, and to preserve the integrity of the delicate surgical site. Infraorbital nerve block is frequently used because it can provide long-lasting pain relief and avoid the complications associated with pain relief drugs. There is a need to asses and synthesise the evidence available so far on the effectiveness and safety of this procedure.


To assess the effects of infraorbital nerve block for postoperative pain following cleft lip repair in children.


Criteria for considering studies for this review

Types of studies

We will include all randomised, published and unpublished, controlled clinical studies which tested peri-operative infraorbital nerve block for cleft lip repair in children compared with other types of analgesia procedure, no intervention or placebo.

Types of participants

We will include children less than 10 years of age, undergoing cleft lip repair surgery.

Types of interventions

Perioperative infraorbital nerve block compared with another intervention (i.e. intravenous analgesia, peri-incisional infiltration), no intervention or placebo. We will consider the type of drug, dosage and route of administration used in each study. For the purposes of this review the term perioperative refers to the three phases of surgery: preoperative, intraoperative, and postoperative, and commonly includes ward admission, anaesthesia, surgery, and recovery.

Types of outcome measures

Primary outcomes
  • Pain measured by valid instruments (e.g. Neonatal Infant Pain Scale - NIPS (Hudson-Barr 2002); The Face Legs Activity Cry Consolability (FLACC) Scale) (Merkel 1997)

  • Duration of postoperative analgesia

  • Adverse effects

Secondary outcomes
  • The need for analgesic prescription for pain

  • Time to first analgesic requirement

  • Heart rate, respiratory rate, and blood pressure

  • Time to feeding after surgery

  • Duration of hospitalisation

Search methods for identification of studies

Electronic searches

We will search the following sources: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library latest issue), MEDLINE, EMBASE, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) from inception to latest issue. The search strategy for MEDLINE is presented in Appendix 1.

Searching other resources

We will search for ongoing trials using the following sites: the metaRegister of Controlled Trials (; The US National Institutes of Health Ongoing Trials Register (, and The World Health Organization International Clinical Trials Registry platform (

We will check reference lists of the included studies to identify any additional studies, and we will contact specialists in the field and authors of the included trials for unpublished data. We will not impose any language restrictions.

Data collection and analysis

Selection of studies

Two review authors (GF and EH) will independently screen the trials identified by the literature search. After merging the search results and eliminating duplicate records, the review authors will examine titles and abstracts to select the relevant reports. Then they will retrieve and examine the full text of selected studies for compliance with eligibility criteria. They will document the reason for exclusion of individual trials and will consult a third review author (EMKS) in case any disagreements arise. They will not include data from trials under scrutiny until a consensus is reached. They will use the PRISMA flow chart diagram to document the screening process (Liberati 2009).

Data extraction and management

Two review authors (GF and EH) will independently extract data using a standard form, and enter data into Review Manager (RevMan 2012). They will resolve disagreements by consensus or by discussion with a third review author (EMKS). The review authors will extract the following information: characteristics of the study (design, setting); participants; type of surgery; interventions; outcomes (outcome measures, timing of outcomes, adverse events); and risk of bias criteria. Where studies have multiple publications, we will use the main trial report as the reference and supplement additional details from secondary papers. We will contact authors from all studies where there is incomplete information about the evaluated outcomes.

Assessment of risk of bias in included studies

We will use the Oxford Quality of Score (Jadad 1996) as the basis for inclusion of studies. We will assess the included studies for risk of bias using the Cochrane Collaboration's tool for assessing risk of bias (Higgins 2011). We will include the following domains in the analysis: sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, sample size and other issues (e.g. extreme baseline imbalance). Two independent authors will determine quality assessment of the data collected, and will resolve any disagreements by consensus or by discussion with a third author. All judgements will be fully described. We will categorise each domain as being at 'low risk' of bias, 'high risk' of bias or 'unclear risk' of bias (either lack of information or uncertainty over the potential for bias). We will complete a 'Risk of bias' table for each eligible study and present the assessment using a 'Risk of bias' summary figure, which presents all of the judgements in a cross-tabulation of study by entry. This display of internal validity indicates the weight the reader may give the results of each study.

Measures of treatment effect

For dichotomous variables, we will calculate the risk ratio (RR) and 95% confidence intervals (CIs). For continuous data, we will calculate mean differences and 95% CIs between treatment groups if studies report exactly the same outcomes. If similar outcomes are reported on different scales, we will calculate the standardised mean difference and 95% CI. The most appropriate way of summarising time-to-event data is to use methods of survival analysis and to express the intervention effect as a hazard ratio, and these data will be taken directly from the results of the studies (Higgins 2011).

Unit of analysis issues

We will base the unit of analysis on the individual participant (unit to be randomised for interventions to be compared), i.e. the number of observations in the analysis should match the number of individuals randomised.

Dealing with missing data

For missing or unavailable data, we will contact the study authors for additional information. In the case of no response, irrespective of the type of data, we will report dropout rates in the 'Characteristics of included studies' tables of the review, and we will use intention-to-treat analysis (Higgins 2011).

Assessment of heterogeneity

We will qualify inconsistency among the pooled estimates using the I² statistic: ((Q - df)/Q) x 100% test, where Q is the Chi² statistic and df represents the degree of freedom. This examines the percentage of total variation across studies due to heterogeneity rather than chance. We will use a fixed-effect model in the absence of substantial heterogeneity (I2 < 50%), otherwise we will use a random-effects model (I2 > 50%) (Higgins 2011).

Data synthesis

Methods of synthesising the studies will depend on quality, design and heterogeneity. We will explore both clinical and statistical heterogeneity. In the absence of clinical and statistical heterogeneity (I2 < 50%) we will apply a fixed-effect model to pool the data. In the presence of statistical heterogeneity (I2 > 50%) we will apply a random-effects model for meta-analysis. Where synthesis is inappropriate we will present a narrative overview.

Subgroup analysis and investigation of heterogeneity

If substantial heterogeneity is found and there are sufficient data, we will investigate the possible causes by further exploring the impact of the condition of the individuals and interventions (i.e. participant characteristics, type and duration of the surgery, type and doses of drugs, adjuvant drugs) using subgroup analyses.

Sensitivity analysis

If there are an adequate number of studies, we will perform sensitivity analyses based on separation of studies according to risk of bias. We will do this by excluding the trials most susceptible to bias based on our risk of bias assessment: those with inadequate allocation concealment; high levels of post-randomisation losses or exclusions; and uncertain or unblinded outcome assessment (Deeks 2011).

Presentation of results

We will present the main results of the review in a 'Summary of findings' table, which provides key information concerning the quality of evidence, the magnitude of effect of the interventions examined, and the sum of available data on the main outcomes, as recommended by the Cochrane Collaboration (Schünemann 2011).


We would like to acknowledge the support of Anna Hobson, Cochrane Pain, Palliative and Supportive Care (PaPaS) Group Managing Editor and Joanne Abbott, Trials Search Co-ordinator.


Appendix 1. MEDLINE search strategy

1. Cleft Lip/
3. (cleft lip* or harelip*).tw.
4. or/1-3
5. Pain, Postoperative/
6. ((postoperative adj4 pain*) or (post-operative adj4 pain*) or post-operative-pain* or (post* adj4 pain*) or (postoperative adj4 analgesi*) or (post-operative adj4 analgesi*) or "post-operative analgesi*").mp.
7. ((post-surgical adj4 pain*) or ("post surgical" adj4 pain*) or (post-surgery adj4 pain*)).mp.
8. ("pain-relief after surg*" or "pain following surg*" or "pain control after").mp.
9. (("post surg*" or post-surg*) and (pain* or discomfort)).mp.
10. ((pain* adj4 "after surg*") or (pain* adj4 "after operat*") or (pain* adj4 "follow* operat*") or (pain* adj4 "follow* surg*")).mp.
11. ((analgesi* adj4 "after surg*") or (analgesi* adj4 "after operat*") or (analgesi* adj4 "follow* operat*") or (analgesi* adj4 "follow* surg*")).mp.
12. exp Surgical Procedures, Operative/
13. or/5-12
14. Nerve Block/
15. Infra-orbital nerve block*.tw.
16. Infraorbital nerve block*.tw.
17. Anesthetics, Local/
18. nerve block*.tw.
19. or/14-18
20. 4 and 13 and 19

Contributions of authors

Protocol stage: draft the protocolEMKS, GF and MRT
Review stage: select which trials to includeGF, EH and EMKS
Review stage: extract data from trialsGF, EH
Review stage: enter data into RevManGF, EH
Review stage: carry out the analysisGF, EMKS
Review stage: interpret the analysisGF, EMKS
Review stage: draft the final reviewGF, EMKS and MRT
Update stage: update the reviewGF, EMKS

Declarations of interest

Gustavo Feriani: None known.

Eric Hatanaka: None known

Maria R. Torloni: None known

Edina MK da Silva: None known