Intravenous Fluids After Cleft Repair Surgery: Do They Enhance or Delay Recovery?

Cleft lip and palate are one of the commonest craniofacial congenital anomalies [1,2]. They may present as an isolated cleft lip or palate or as a combined defect, as a solitary complaint or as part of a syndrome. All presentations create a burden on physical, mental, and psychological health of patients and relatives [3]. Cleft defects may be isolated or part of an underlying congenital syndrome [2]. If left untreated, apart from aesthetic disfigurement, clefts may present a number of functional complications such as swallowing and feeding difficulties, limited maxillofacial development, speech and hearing problems and recurrent ear infections [3,4].

A multidisciplinary team is required for holistic management of cleft lip and/or palate repair made up of plastic surgeons, otolaryngologists, maxillofacial surgeons, specialised nurses, speech therapist, audiologist, psychologist, geneticist, and dentist [2,5]. Cleft repair surgery occurs early on in life with cleft lip ideally repaired in the first three to four months of life and cleft palate operated on in the first six to twelve months of life [3,6]. Timing of surgery is usually dictated by size and age of the baby and repair is usually planned early enough to optimise anatomy for timely development to achieve proper function [7].

Feeding post operatively is a controversial topic and different centres initiate mandatory or optional intravenous fluid regime as opposed to oral feeding only [6,8]. Intravenous fluids are a form of homeostasis used to replace fluid losses [9]. They are usually used to replace extracellular fluid losses, correct electrolyte imbalances and provide a source of glucose.

Infants have higher fluid requirements than adults mostly due to a higher metabolic rate and great caloric expenditure and also due to higher total body surface area to weight ratio, resulting in increased water losses in comparison to adults. The higher respiratory rate in infants also accounts for extra losses [10]. Clefts pose an additional possible source of fluid losses due to difficulty feeding, especially in cleft palate.

During the perioperative period, patients experience additional fluid losses. In children, clear fluid intake is allowed up to one hour before surgery [11]. Anaesthetists usually apply the Holiday and Segar formula to calculate fluid requirements in paediatric patients and this is included in a number of guidelines including APA and NICE guidelines. Isotonic fluids with low glucose concentration (1 – 2.5%) are the fluids of choice in paediatric patients less than two years old [12]. Both hypoglycaemia and hyperglycaemia may cause neuronal injury so administering 5% dextrose without any considerations may also be harmful.

Arguments in favour and against post-operative intravenous fluids are presented in Table 1.

Table 1: Arguments in favour and against post-operative fluids only [6,8].

This review aims to assess the necessity of fluids post-operatively to enhance recovery. Length of stay in relation to post-operative fluid requirements will be assessed as a secondary outcome.

Table 2: Aim as per PICO Framework.

Search Strategy

An online search was conducted on Ovid Medline to answer the research question. Data from 2012 to 2022 in English language was considered. This ten-year period was chosen to obtain most recent results about the topic and cover ongoing studies.

Studies retrieved were mostly retrospective observational studies. No randomised controlled trials were identified owing to the limited research available on the topic.

Two full articles will be considered for this literature review while selective data will be extrapolated from another study. Selection was based on satisfying as many criteria of the inclusion and exclusion criteria. Literature will be evaluated using the Critical Appraisal Skill Programme (CASP) checklist [13] and graded by the Harbour and Miller [14] hierarchy of evidence.

The studies considered include:

1) Clinical Factors Affecting Length of Stay After 100 Consecutive Cases of Primary Cleft Lip Repair by Oh et al. [15]

2) Should We Give Routine Postoperative Intravenous Fluids After Cleft Surgery? by Onyekwelu et al. [8]

3) Post-operative intravenous fluid administration for infant cleft surgery: an observational study by Rangaraju et al. [6]

Oh et al. [15] explore the Clinical Factors Affecting Length of Stay After 100 Consecutive Cases of Primary Cleft Lip Repair. They investigated cases of children who underwent primary cleft lip repair at a tertiary centre through a retrospective cohort study. The main aim was to assess the course of hundred consecutive infants and analyse the length of stay and factors contributing to it, one of which being intravenous fluid requirement and time to return to oral feeding. The main conclusion from the study was that outpatient or short-stay observation is questionable.

For the purpose of this assignment, all the paper’s content will be included but results relating to intravenous fluids only will be considered in the discussion.

Table 3:

The main rationale behind this study is to challenge traditional practices within the United States, namely routine admission after primary cleft lip repair surgery. The aim of the study was clearly stated at the beginning with primary and secondary targets to be able to reach this aim. The authors declared no conflict of interest and obtained the necessary ethical approvals in keeping with Declaration of Helsinki regarding research ethics.

Inclusion criteria were set as in Table 5. Exclusion criteria were not specifically mentioned and may introduce risk of selection bias and inconsistency when choosing the sample.

Table 4:Aims, methods and results for Oh, et al. (2015) [15].

Consecutive patients through convenience sampling were selected for the study. The study is single centred and not powered hence increasing risk of Type II error and decreasing external validity.

Statistical significance was set at 5%. Tests used for analysis are mentioned but there is no explanation relating to which test was used in categorical versus non-categorical data, for example use of t test in continuous variables. Results are analysed through univariable analysis but multivariate analysis is not available. Thus, one cannot assume if results are due to significance or covariance. This leads to decreased statistical rigour. Univariate analysis for this study is displayed in Figure 5. Descriptive statistics regarding intravenous fluids are provided however the authors fail to provide graphic representation of the results.

A standard surgery is carried out in all cases within the studymodified rotation-advancement Millard repair-yet there is no mention whether the same surgeon operated all infants, level of expertise and follow up. These factors may introduce information bias. There is also a high degree of variability and decreased sensitivity of the study.

The main outcome of the study is that a day surgery for elective primary cleft lip repair is not ideal with questionable safety. This result might be due to more factors tested including patient factors hence higher chance of obtaining unfavorable factors for a day surgery. Intravenous pain medication requirements are also considered.

The authors refer to the limitations of the study by mentioning that follow up data is not documented. They also appreciate that the study has small patient numbers which limits the power of the study. They suggest that a prospective design would provide more reliable conclusions.

In conclusion, postoperative oral intake was found to correlate with shorter length of stay. However, this was not well implemented in this retrospective study with patients having longer stay due to longer intravenous fluid administration. A well-designed prospective study is suggested by the authors to confirm these results. The study may be graded as Harbour Miller 2- due to high risk of bias and confounding.

The second retrospective cohort study tackles fluid management after cleft repair surgery. Contradicting management strategies exist, hence Onyekwelu et al. [8] question Should We Give Postoperative Intravenous Fluids After Cleft Surgery? The single-centred study identifies seventy-nine patients operated by a single surgeon at Manchester Cleft Unit between August 2011 and August 2012. The study was driven by a previously conducted study between 2006 and 2008 showing that patients in Manchester had a 30% longer length of stay partly related to a standard overnight intravenous infusion post-operatively and slower but continuous intravenous fluid regimen until regular oral feeding was restored. This was criticised and as a reaction to the study a trial of no routine fluids was carried out by the authors in 2011. The authors include the geographical location of the study so that the reader can

The aims of this study were well defined with clear outcomes - to identify intravenous fluid requirement, adverse events and length of stay. The key finding from this study is that routine intravenous fluids are not indicated post- operatively. None of the patients required readmission or second surgery indicating that routine fluids are not a key factor in limiting post-operative adverse events.

The aim, methods and results are summarised in Table 6.

Table 5: Inclusion criteria for Oh et al. (2015) [15].

The objective of the study is well defined since it targets the research question, hence designing the study as a direct reply to the aim. Secondary outcomes are also incorporated in the aim, making the study more structured and targeted. Data collection methods are explained. The patient’s characteristics included from data collection are also mentioned in the study making the study reproducible.

Authors declared that the study is endorsed by national research review board, however they failed to mention conflicts of interest relating to the study. This reflects negatively on the study due to a higher probability of misconduct as individuals may divert resources including finances towards personal gains any may decisions for private benefits. Failure to dissociate from any conflicts of interest also implies lack of research governance and has a higher risk of reduced scientific quality. Should there be a conflict of interest in a study, then there would also be a breach of the Declaration of Helsinki [16].

The inclusion and exclusion criteria are not mentioned as definite points, resulting in decreased reliability and inconclusive results. Only general reference is made to the population included as ‘All patients undergoing cleft-related surgery by the senior author in a single centre during August 2011 through August 2012’. Consecutive patients are incorporated in the study, selected by convenience sampling as the patients in a set timeframe were included. Unselected patients specifically limit selection bias.

Sample size is not adequately calculated and a power calculation is unfortunately missing. The sample size is limited due to single-centred study data covering only one year period, therefore reducing external validity and increasing risk of Type II error. Single centred studies are less expensive, small scale studies with a flexible approach to develop new treatments or put research to practice. However, the small cohort in this type of study might result in recruiting a very small population to be scientifically viable. Additionally, there is a higher risk of bias when compared to a multi centred study as investigators are from one centre only

The authors mention a number of standardised criteria, including perioperative fluid balance, surgeon expertise and follow up by specialised nurses in all cases. This reduces the risk of observer bias.

Results were presented through text with limited graphic representation. Graphs were only used to present types of surgeries carried out and requirement of post-operative intravenous fluids in the older and younger groups of patients. Statistical analysis was set at 5% indicating that a p value lower than 0.05 would reject the null hypothesis and accept the alternative hypothesis indicating a statistically significant result. Significant p value was obtained for older children and intravenous fluids indicating a statistically significant relationship between the two variables. The Mann- Whitney U-test is an adequate test which was used to analyse statistics.

The study fails to mention a univariate or multivariate analysis. In view of this, it is difficult to identify whether results are due to covariance or otherwise. Validity is also questionable, and the study has poor statistical rigour.

Onyekwelu et al. [8] make a comparison with length of stay and complication rate of other units, namely Oxford and Great Ormond Street Hospital. Additionally, they compare physiological reserve of children undergoing cleft surgery and adenotonsillectomy. These surgeries are compared due to similar risks of bleeding, dehydration and airway distress [17-19]. These comparisons increase transferability of information and add external validity to the study.

The study concludes that routine post-operative intravenous fluids are not indicated for a faster recovery. Instead, the authors advocate early post-operative feeding as this is associated with shorter length of stay and no adverse events. This contradicts previous study by Oh et al. [15] whereby shorter length of stay is refuted. Onyekwelu et al. [8] tackle all the aims of this retrospective cohort study. The study would be graded as 2- according to the Harbour and Miller classification as it is a small single-centred study with lack of complete statistical analysis. Further studies with a larger cohort and more centres are required to improve external validity and obtain more transferable results to be able to change existing practices.

Rangaraju et al [6] carry out post-operative intravenous fluid administration for infant cleft surgery: an observational study. The retrospective cohort study analyses one hundred and ten cleft repair surgeries at West Midlands Cleft Centre carried out between May 2015 and April 2016 in non-syndromic patients. The primary aim was to investigate intravenous fluid therapy for primary cleft surgery, time to oral feeding post operatively and length of stay in hospital.

Authors concluded that infants with cleft lip repair had the shortest length of hospital stay which was even shorter with no intravenous fluids. Cleft lip patients also started oral feeding earlier without intravenous fluids, hence indicating that routine intravenous fluids are not indicated.

The aim, methods and results are summarised in Table 7:

Table 6: Aims, method and results for Onyekwelu, et al. [8].

The aim of the study is defined straightaway at the beginning of the manuscript hence the study is well designed to test the hypothesis. Data collection tools were selected carefully to be able to reach the desired aims. Through stepwise instructions for data collection, the authors ensure consistency hence increasing reliability of the study. Inclusion and exclusion are set out as demonstrated in Table 8.

Table 7: Aims, method and results for Rangaraju, et al. [6].

Table 8: Inclusion and exclusion criteria for Rangaraju, et al. [6].

The fact that both inclusion and exclusion criteria are highlighted limits risk of confounding. However, there is no mention of selection methods for the patient cohort indicating that there might be risk for selection bias. Additionally, the study lacks a power calculation with a subsequent small sample size from a single centre only hence increasing risk of Type II error. Although being a small cohort, the study population is the largest of the three studies analysed in this review. Selection bias and absence of power calculation will provide unreliable results hence decreasing external validity of the study. The authors fail to mention method of selection of patients hence increasing risk of selection bias.

Surgeons performing the procedures were limited to three surgeons practising at the study centre maintaining consistency and standardization of practice. One of the surgeons manages post-operative fluids while the other two surgeons depend on anaesthetists to manage post-operative fluid requirements. This may introduce risk of confounding.

Rangaraju et al. [6] declare no conflict of interest however fail to mention ethical approvals. All studies involving human or animal studies are legally bound to have informed consent and ethical approval [20] to achieve good research governance. Hence this study has poor research governance due to missing ethical approvals and implies a breach to the Declaration of Helsinki [16].

Statistical analysis was carried out using adequate statistical tests. In fact parameteric data was rightly tested with ANOVA and post-hoc Tukey test. p value of less than 0.05 was considered significant. A univariate analysis was done and is represented in a table but no multivariate analysis was carried out, increasing risk for covariance. This poses a threat to statistical rigour and limits external validity.

Results are presented in categories namely (i) Fluid Prescription and Administration, (ii) Length of stay in hospital and (iii) Oral intake. These categories tackle the aims directly. Text and tables are presented with no graphs within the text. Figure 3 compares operative groups and fluid requirements. Length of stay and time to achieve >50ml oral intake are not related to intravenous fluids. In fact, length of stay and time to oral intake in patients who received intravenous fluids were not found to be statistically significant in relation to surgery with p values >0.05 as shown in Figure 1.

The authors list the limitations of the study namely a small sample of hundred and ten surgeries. Group sizes were noted to be smaller when split into different surgery groups. The study also fails to identify complete versus incomplete cleft palates. Additionally, there is no distinction between palate surgeries requiring or not requiring release of incision.

The study concludes that routine post-operative fluids are not indicated but should only be given in cases of poor oral intake. Infants who received no post-operative intravenous fluids were discharged earlier from hospital. This can be seen more clearly in lip only infants. Some patients with cleft repair required intravenous fluids to maintain hydration and further studies are necessary to make any recommendations regarding cleft palates.

Data relating to routine post-operative fluids after cleft lip or palate repair is inconclusive. In fact, within the three studies considered two studies advocate for no routine intravenous fluids [6,8] while Oh et al.

[15] stick to more conservative treatment with routine postoperative intravenous fluids. this controversy, all studies agree that early oral intake leads to shorter length of stay, hence enhanced recovery. Thus, as a reply to the aim, all studies infer that routine post operative intravenous fluids do not provide a clear-cut additional benefit to cleft lip and palate repair surgeries.

Intravenous fluids were found to increase length of stay unnecessarily. Hence Onyekwelu et al. [8] and Rangaraju et al. [6] promote early oral feeding and intravenous fluids only in case of insufficient feeding.

It must be appreciated that all three studies were graded 2- according to Harbour and Miller [14] classification meaning that all have a high risk of confounding or bias. Unfortunately, this might be due to all three studies being non-powered with a risk of Type II error, possibly due to small cohorts and single- centred data. These limitations are common to the studied literature. In view of this, more rigorously conducted studies are required with greater sample size from a multi-centred cohort.

In conclusion, the future points to elective cleft lip and palate day surgery with no routine intravenous fluids and early oral intake. However, only limited data is available to date as indicated in the search strategy and further studies are required.

None.

No conflict of interest.

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