Anaesthesia for Cleft Lip and Palate Surgery : Study from a Hospital of Eastern Nepal

This is retrospec ve study conducted on cle lip and palate repair pa ents between the ages of 3 months to 12 years, operated under general anesthesia during last six years at Morang Co-opera ve Hospital, Biratnagar, Nepal. Total 570 pa ents were assessed with preopera ve, intraopera ve and postopera ve parameters, complica ons and managements. The MS Excel office and SPSS so ware was used to analyze the data.


INTRODUCTION
Orofacial cle s (OFC) are the most common congenital birth defect of lip, palate, or bothcaused by complex gene c and 1,2 environmental factors.It occurs due to the failure of fusion or break in fusion of nasal and maxillary processes with the th pala ne shelves, which form during 8 week of the 3 embryonic period.Orofacial cle s present as part of the phenotype in over 600 specific gene c syndromes, more 4 commonly in associa on with isolated cle palate.Smoking, vitamins and folic acid deficiencies, alcohol consump on and use of non-prescrip on medica on by pregnant women are 5 predisposing environmental factors of orofacial cle s.Early repair is more important for the outcome of surgery and according to American Cle Palate Associa on guidelines, cle lip should be repaired within 6 months of age and cle 6 palate within 18 months.This centre has special cle clinic established by the na onal NGO Phect Nepal and opera ng since 1999.
Oral-facial cle s are a major public health problem and the global average for the number of people born with cle is about 1 in every 500 to 750 live births and every three 1 minutes a child is born with a cle lip or cle palate and 3 isolated cle palate seen in 1 in 2000 live births.Cle lip with or without cle palate reported more in the males but 7 isolated cle palate seen more in females.There is a wide varia on in the occurrence of cle s among different ethnic groups.In USA, Asian and Na ve American popula ons have prevalence rate of 2 per 1000, Europeans have 1 in 1,000, and 8 African-derived popula ons have about 1 in 2,500.Das et al stated that Asians have the highest risk 1.4: 1,000 births followed by whites 1: 1,000 births and African Americans 9 0.4 : 1,000 births.In SAARC countries India has the incidence of 1.4 per 1000 live births according to the survey of Indian Affected children have a range of problems including feeding difficul es due to problems with oral seal, swallowing and nasal regurgita on, poor dental development and other associated problems like hearing difficul es due to abnormali es in the palatal musculature, and speech difficul es due to nasal escape and ar cula on problems.Thus, cle s have a prolonged, adverse influence on the 16 health and social integra on of affected individuals.
In 2008, the World Health Organiza on (WHO) has recognized that non-communicable diseases, including birth defects cause significant infant mortality and childhood morbidity and have included cle lip and palate in their 2 Global Burden of Disease (GBD) ini a ve.
Periopera ve management of pa ents can be challenging in resource limited country like Nepal.These pa ents o en presents with airway problem making it crucial job during anaesthesia.The other associated congenital anomalies can alter the anaesthe c management.Till now there is no literature from Nepal defining demographic, clinical profile and intraopera ve challenges and hence this study can be a milestone for the intraopera ve management of pa ents with cle disorder.

MATHODOLOGY
Total 570 children were analyzed between the ages of 3 months to 12 years of age operated at Morang co-opera ve hospital from Jan 2010 to Dec 2015.The electronic recording was started in this hospital from 2010 and this is a retrospec ve record analysis of all the details of pa ents operated a er 2010.Study started a er ge ng approval from the hospital authority.In this Centre cle lip is operated from the age of 3 months and palate from 10 months.

Inclusion criteria
Pa ents with cle lip with or without cle palate and isolated cle palate from 3 months of age to 12 years with ASA I and II physical status.

Exclusion criteria
1. Children above 12 years and below 3 months of age 2. Pa ents with other congenital anomalies like congenital heart disease, duodenal atresia etc.
All the collected pa ents were taken for the preopera ve evalua on by surgeon, pediatrician and anesthesiologist and suitable babies were admi ed for the prepara on of surgery.During admission detailed discussion done regularly with the parents about the surgery, anesthesia, outcomes, risks and follow ups and get the informed consent for surgery.Rou ne preopera ve evalua on and basic inves ga ons including complete blood count, chest x-ray,urine analysis, height and weight measurements done to evaluate the babies and a er ge ng all reports, set a plan for the surgery.No preopera ve seda ve premedica on given and rou ne preopera ve fas ng guidelines ins tuted for prepara on.
At the day of surgery IV line was opened at the preopera ve room just before the surgery or directly at the opera on room with 22/24G IV canula.Anesthesia management depends upon the types of the defect of the baby.Two types of anesthe c management applied including general anesthesia(GA) with endotracheal intuba on and total intravenous anesthesia(TIVA).TIVA was used for the management of children with unilateral incomplete cle lip with the age of two years or above and rest of the pa ents operated under GA.All pa ents received IV preopera ve seda on of inj atropine (0.02 mg/kg) not less than 0.1mg and inj midazolam (0.05 mg/kg) at the opera on table.The intraopera ve monitoring included ECG, pulse oxymetry, noninvasive blood pressure(NIBP), temperature and a precordial stethoscope.To manage the heat lost the temperature of opera ng room was adjusted within 23-25°C along with warm blankets and caps to cover the baby.Out of 570 pa ents 539 operated under general anesthesia with endotracheal intuba on and rest 31 babies under total intravenous anesthesia(TIVA).Intraopera ve fluid used in this centre for babies was Isolyte P which is a solu on of 5% dextrose with 0.3% NS, Magnesium and potassium.Calcula on of fas ng and intraopera ve fluid requirement calculated according to the 4-2-1 rule.
All babies induced with IV ketamine (2mg/kg) and Propofol up to the 2-3mg/kg and a er tes ng the eye lid reflex the anesthesia mask was applied with oxygen and halothane.
A er successful ven la on, succinyl choline(2mg/kg) given to facilitate intuba on.When muscle relaxa on was adequate laryngoscopy was performed using Macintosh blade and preformed south facing RAE endotracheal tubes were used for intuba on and the tube is fixed properly at the centre.During laryngoscopy, external laryngeal compression was used rou nely for be er visualiza on of larynx.No of a empts for successful laryngoscopy and intuba on recorded and discussed in results.Long ac ng muscle relaxa on Inj vecuroneum o.1 mg/kg IV used in some cases if required.inj tramadol 1mg/kg intravenously used for analgesia.The circuit used in this center was Meplesan D in all cases.Anesthesia was maintained by 100% Oxygen and 0.75-1.5% halothane.For TIVA group a er inj atropine and inj midazolam, intermi ent dose of inj ketamine and propofol used with bilateral infraorbital block.The addi onal analgesia in all cases also provided by surgeons during administra on of inj xylocaine with adrenalin in the opera ve field.In this centre the strength of Inj adrenalin with xylocaine used is 1: 100000 prepared a er mixing with 0.5% bupivacaine to prolong the analgesia in postopera ve period.The average requirement of dose of the adrenaline for the infiltra on was 3-5 ml (30-50 microgram) in cle lip cases and 12-15 ml (120-150 microgram) in cle palate cases.
Halothane was stopped always during the infiltra on of adrenalin and anesthesia was maintained with inj ketamine and inj propofol to prevent the halothane induced cardiac arrhythmias.Broadspectrum an bio c used intravenously for all babies before surgical incision.
At the end of the procedure residual neuromuscular block was reversed using inj neos gmine if it was used during surgery.In this centre both deep and awake extuba on method is used depending upon the condi ons.Easily intubated cases planned for deep extuba on if the baby remains quite with adequate rate and depth or respira on at the end of surgery.Extubated babies were watched carefully and if all the parameters were normal then the babies placed on the lateral posi on with all monitors a ached in opera ng room ll the babies fully revived.The awake extuba on plan applied to all difficult intuba on babies and those babies who fight at the end of surgery even without decreasing the depth of anesthesia.Throat was rou nely checked at the end of the procedure to confirm the removal of the throat pack and to observe clots and any foreign bodies and ongoing bleeding before extuba on.Babies were transferred to the postopera ve room when they fully awake and start to cry.In some cases when there was preopera ve snoring or prolong postopera ve airway obstruc on, a tongue s tch is placed which pulls the tongue forward and clear the airway and prevent from postopera ve airway obstruc on.Close observa on required for these cases into the recovery period.Once the child was fully awake, no bleeding from the wound and no crying then feeding with the clear fluid begins.
No regular IV fluids given to the babies in the postopera ve period and IV infusion prescribed only if the babies were not able to take fluids orally.
Appropriate analgesia is very important among the babies too and for postopera ve analgesia intrarectal paracetamol (10-15mg/kg) used rou nely at the end of the surgery.Once the babies able to drink they were prescribed with the suspension of paracetamol and ibuprofen orally.All intraopera ve and postopera ve complica ons were recorded properly.All the collected data was entered in MS Excell andanalysed by SPSS.For the data analysis all babies were grouped into the four groups: 3 months -2 years, 2 -5 years, 5-9 years and 9-12 years.

RESULTS
During the six years of the study period, Centre have operated 570 facial cle cases with the age of 3 months to 12 years under general anesthesia.The details of age, sex and types of cle are given in the table 1 and 2. (2.86 %), no consent 1 (0.17%), and surgical site skin infec on 3(0.52%).
Out of 570 surgeries 109 pa ents had intra opera ve complica ons, among them84(14.73%)had minor complica on and 25(4.38%) had major (table 3).Tachycardia seen in 47 pa ents and was the most common minor complica on seen followed by hypoxia (n= 39) and hypothermia (n=26).
Ventricular extrasystoles seen in 23 pa ents during administra on of inj xylacaine with adrenalin and 2 pa ents developed bradycardia a er extuba on.Difficult intuba on was defined if laryngoscopic a empt was more than two 17 mes and difficult intuba on seen in 21 pa ents in this study.One pa ent was cancelled due to failed intuba on and referred to our Kathmandu centre.Endotracheal tube compression seen in 4 cases due to the ght placement of the retractor.Laryngospasm was seen in 5 cases which were managed by inj succinyl choline and posi ve pressure ven la on.Bronchospasm was seen in 8 cases.Respiratory obstruc on seen more frequently a er extuba on and seen in 37 cases and postextuba on coughing was seen in 23 pa ents.
In postopera ve period, 1 cle lip pa ent developed hematoma a er injury and 9 cle palate pa ents had postopera ve wound bleeding on the same day of surgery.None of the pa ents required intraopera ve and postopera ve blood transfusion.
No ketamine related hallucina ons seen in the postopera ve period.Hypothermia is defined as a core temperature below 36°C and it is also one of the most common periopera ve disturbance in pediatric pa ents and the incidence of hypothermia can be up to 20% in major surgical pediatric 35 patents.In a study done by Brinda et al the occurrence of hypothermia was 3.1% and was due to the prolong opera on me and therefore shortening of dura on of surgery is quite 31 important to prevent hypothermia.In thisstudy 26(4.56%)pa ents developed hypothermia during surgery.
In cle surgery surgeons are using high concentra on of adrenaline to achieve a blood less field and in this study the concentra on of adrenaline used was 1: 100000.The solu on of adrenaline used in cle lip was 2-5 ml and for the cle palate 10-15 ml only.Cardiac arrhythmia is closely related with the use of vasopressor with halothane and in the finding of Hirshom et al ventricular arrhythmias occurred quite frequently in halothane anesthe zed pa ents when a 36 small amount of adrenaline was injected.For the preven on of such arrhythmias author has suggested to use the lowest concentra on of halothane, use of concentra on of adrenaline at 1:100000 or 1:200000 strength, injec on of vasopressor periodically and avoid combined use of halothane and vasopressors and regular use of ECG monitor 36 for anesthesia.The concentra on of adrenalin used in this centre is 1:100000 and for the preven on of complica ons, the adrenalin solu on is injec ng in the opera on site periodically and always a er discon nua on of the halothane.During injec on of vasopressor,anesthesia is maintained with intravenous propofol and ketamine.Criteria of tachycardia in this study were 50% rise in the heart rate than the base line and bradycardia if the heart rate was less than 80 beats per minute.In this study 47 pa ents developed tachycardia 2 cases developed bradycardia a er extuba on andventricular extrasystoles seen in 23 pa ents.So the total cardiovascular complica on seen in this study was in 72(12.63%)pa ents.

CONCLUSION
Anesthesia for the cle lip and palate surgery in infants and children is always carries a great challenge to the anesthesiologist due to the number of periopera ve complica ons.Anesthe c management of the opera ve team must have skilled and experienced medical persons, appropriate intra and postopera ve monitoring equipments, essen al airway devices and advanced postopera ve care set up to minimize the complica ons.

10 health
ministry in 2010.In Pakisthan the prevelance rate is 11 1.91 per 1000 live births and in Nepal the accepted 6 prevalence rate is 1.64 per 1000 live birth.Orofacial cle s might be syndromic if accompanied by addi onal structural abnormali es and nonsyndromic if they occur in isola on without other apparent abnormali es.About 70% of cle lip with or without palate are non 12 syndromic.Syndromes are more frequent in pa ents with cle lip and palate (32%) than in pa ents with cle lip alone(11%) or pa ents with cle palate alone(22%) in Indian 13 pa ents.About 150 syndromes may be associated with cle deformi es.The most well-known are the Pierre Robin's, Treacher Collins and Goldenhar syndrome.Congenital heart 14 disease occurs in 5-10% of these pa ents.The breakdown for the types of cle s is approximately 45 percent cle lip and palate, 35 percent cle lip, and 20 15 percent Cle palate.Cle lip has a male to female ra o of about 2:1, and male to female ra o reported is 1:2 in isolated 10 cle palate.Unilateral Cle lip is more common than bilateral, and for pa ents with unilateral Cle lip, there is a 8 2:1 ra o of le to right sided cle s.

Figure 2: Frequency of intraopera ve respiratory complica ons
Among the operated babies 208 (36.50%) were from the high mountain and hilly regions and rest 362(63.50%)fromTarai.Pa ents required few hours to two days to reach the hospital.Out of 570 cases only 31 (5.43%) babies operated under TIVA and rest under GA with endotracheal intuba on.This study shows that the prevalence of orofacial cle was the male dominated and among them 352 babies (61.75%) were males.While observing the types, 202 babies (35.43%) were with cle lip only, 43 (7.54%) babies with cle palate only and 325 (57.01%) with cle lip and palate combined.About the procedure 386 (67.71%) babies were operated for cle lip and rest 184 (32.28%) for cle palate.Out of 732 babies 162(22.13%)cancelled and rest admi ed for the surgery.The most common medical condi on causing cancella on was Acute Respiratory Infec on 137(18.71%),Malnutri on 21

Table 3 : Intra opera ve complica ons Complica ons Number of Pa ents Percentage
-5 years of age and about 10% cases above 5 years of age, so only 30% babies appears for the surgery at the age of below 2 years.This late presenta on was mainly due to the unaware of availability of the service.Richard et al also reported about the cause of the late presenta on of pa ents for the cle surgery in Pokhara, Nepal and found that 31% 25 cause was unaware of the availability of the service.In Nigeria only 40% babies came for the cle surgery before the During the 6 years of the study period, there was no death occurred and no any child referred to the higher Centre due to postopera ve complica ons.One pa ent canceled due to failed intuba on and send to Kathmandu cle centre.In the study of large no of cases Triet et al reported 1 death in 40240 cases and Fisher et al reported 4 deaths in a large voluntary wound bleeding, desatura on and laryngospasm.The risk of periopera ve respiratory adverse events is less if muscle 30 relaxa on used for tracheal intuba on.There were no cases of difficult ven la on a er induc on of anesthesia in this study and Inj succinyl choline given only a er successful manual ven la on of lungs.In the present study, 97(17. 29SCUSSIONRoldan et al published an ar cle "ten-Year cle Surgery in Nepal" in 2016 and reported that pa ents were travelling from several parts of the country, taking up to 5 days to reach 18 the hospital.Pa ent selec ons during preopera ve evalua on are very important for the safety of anesthesia in Ideally cle lip should be repaired within the 6 months of age 24 and cle palate before the development of speech or 2 yrs.According to the guidelines of this centre, cle lip is repaired a er 3 months of age and at least 5 kg of weight and cle palate a er 10 months of age 10 kg of weight and hemoglobin 10 gm/dl.Among 570 cle surgeries 347 (60.87%) were between 2obstruc on and coughing but as severe complica ons laryngospasm and desatura on also occurred more a er the extuba on.Coughing itself is usually not a complica on, it is a physiological response to protect the airway from 29 aspira on.However, coughing may increase blood pressure, heart rate and persistent coughing might be associated with other complica ons like saliva on, airway obstruc on,29