Clinical Profile and Outcome of Mechanically Ventilated Neonates in a Tertiary Level Hospital

Introduction: Many sick neonates admitted to neonatal intensive care unit (NICU) require mechanical ventilation but it is associated with various complications and the outcome of neonates is unpredictable. This study aims to identify the indications for mechanical ventilation, complications, co-morbid conditions and outcome of those neonates in terms of survival. Materials and Methods: Retrospective observational study of all neonates who underwent mechanical ventilation from 1 January 2014 to 31 December 2014 in NICU, Tribhuvan University Teaching Hospital. Medical records of the patients were retrieved from hospital record section to collect the relevant data. Results: One-third of admitted neonates in NICU required mechanical ventilation (MV). Commonest indication was severe respiratory distress (70%) followed by perinatal asphyxia (12%) and recurrent apnea (8%). Disease pattern were sepsis (37.2%), RDS of prematurity (17.6%), perinatal asphyxia (11.7%), meconium aspiration syndrome (9.8%), apnea of prematurity (7.8%) and congenital pneumonia (4%). Hospital acquired sepsis was a major complication occurring in 47% patients on mechanical ventilation. Survival rate among neonates on MV was 33%. Survival was better with increasing birth weight and gestational age. Survival was 100% in congenital pneumonia, 50% in perinatal asphyxia, 50% in recurrent apnea, 26% in sepsis, 20% in MAS and 0% in RDS of prematurity. Conclusion: Survival rate of neonates on mechanical ventilation in NICU was 33%. Sepsis was a major problem in NICU, which must be addressed to improve outcome. J Nepal Paediatr Soc 2015; 35(3): 218-223.


Introduction
T he fall in neonatal mortality rate in Nepal has been steady, and has been documented by WHO as 24.4 per 1000 live births in 2012 1 .Sustainable Development Goals target to reduce neonatal mortality to atleast as low as 12 per 1000 live births by 2030 2 .Improving intensive care facili es for the neonates in the country could be one of the eff ec ve interven ons to achieve this.Eff orts must be towards improving and sustaining the neonatal intensive care units at ter ary care centers as well as to establish more level II and III care facili es in the district hospitals and other centers at the periphery.Mechanical ven la on is an essen al part of the neonatal intensive care facility.However, the eff ec ve func oning of NICU, depends not just on expensive high technology equipments and complex infrastructure, but also on medical and nursing exper se and mul disciplinary support from laboratory, radiology, physiotherapy, etc.
Currently, there are several medical colleges and private hospitals providing intensive care for neonates in Kathmandu.Tribhuvan University Teaching Hospital (TUTH) being a ter ary care referral center receives many obstetric referrals for maternal or fetal condi ons and neonate referrals from all over the country with the expecta on of be er neonatal outcome.
Many of these admi ed newborns are cri cally sick and require mechanical ven la on.The survival of sick neonates have improved signifi cantly with the widespread use of mechanical ven la on in NICUs 3,4   .Several studies show that weight and gesta onal age are major determinants of neonatal mortality 4,5 .It is also related with severity of illness at admission, complica ons related to ven lator techniques and strategies and occurrence of co-morbid condi ons like sepsis, coagulopathy, mul organ dysfunc on, congenital malforma ons etc 5,6 .
There is paucity of data about outcome of neonates undergoing mechanical ven la on and its various complica ons in our country.These parameters would be useful to evaluate the func oning and outcome of NICUs as well as to prognos cate the admi ed newborns.The present study aims to iden fy the common indica ons for mechanical ven la on, possible correla on of underlying diseases with survival of neonates and complica ons occurring during mechanical ven la on.

Material and Methods
This was a retrospec ve observa onal study of all neonates who underwent mechanical ven la on from 1st January to 31st December, 2014 in NICU, TUTH.Medical records of the pa ents were retrieved from hospital record sec on to collect the data, regarding gesta onal age, birth weight, mode of delivery, apgar scores, maternal medical issues, admi ng diagnosis, indica on of mechanical ven la on, dura on of mechanical ven la on and outcome.Occurrence of any complica ons during ven la on like pneumothorax, hospital acquired sepsis, ven lator associated pneumonia, DIC, pulmonary haemorrhage, and other co-morbid condi ons like shock, acute kidney injury, sepsis, intraventricular haemorrhage, necro zing enterocoli s were recorded.All neonates were grouped into two -"survivors" and "non-survivors".Birth weight and gesta onal age was sub-grouped into 4 and 5 groups respec vely and its rela on to survival rate was analyzed using chi square test.Associa on of various complica ons with outcome was analysed by univariate analysis and odds ra o was calculated.P-value less than 0.05 was considered sta s cally signifi cant.The data was entered and analyzed using SPSS 16.

Results
There were 174 babies admi ed in NICU in January-December 2014.Out of them, 56 were ven lated, cons tu ng 32% of the admi ed neonates in NICU.Among them, the detail records of only 51 could be retrieved, so were included in the study.There were 17 survivors (33.3%) and 34 non-survivors (66.7%).Nine babies who were discon nued from medical care when they became cri cally ill were also included in the "non-survivor" group.There were 34 males and 17 females.Majori es (94%) were inborn babies, among which 19 babies were born by vaginal delivery, one underwent vacuum applica on and 31 were delivered by caesarian sec on.Indica ons for caesarian sec on were maternal eclampsia, severe pregnancy induced hypertension, antepartum hemorrhage, maternal cardiac disease, oligohydramnios, fetal distress, meconium stained liquor and premature rupture of membrane.Antenatal steroid was received by 13 mothers.
There were three babies weighing less than 1000 grams, 15 babies between 1000 -1499 grams, 11 between 1500 -2499 grams and 22 babies weighing more than 2500 grams.None of the neonates weighing less than 1000 grams survived, half of those weighing more than 1500 grams survived.There were 23 (45%) preterm babies and 28 (55%) term babies.None of the neonates less than 32 weeks gesta on survived.Survival rate gradually increased with increasing gesta onal age, 26.6% in 32-33 weeks, 33.3% in late preterm (34-37 weeks) and 50% in term(>37 weeks).Table 1 shows par culars of the neonates in rela on to survival rate.The survival rate was signifi cantly related to birth weight of neonates (p-value=0.019) and gesta onal age of neonates (p-value 0.039).
The disease pa ern in mechanically ven lated neonates is shown is Table 3 with respec ve survival outcomes.Most common was sepsis in 19 pa ents (37.2%) including pneumonia, meningi s, necro zing enterocoli s.Respiratory distress syndrome of prematurity was present in 9 (RDS 17.6%), meconium aspira on syndrome in 5 (MAS 9.8%), birth asphyxia in 6(11.7%),apnea of prematurity in 4 (7.8%),congenital pneumonia in two, congenital heart disease in one, pneumomedias num in two, congenital diaphragma c hernia in one and for post opera ve surgical care in two pa ents.Time of ini a on of ven la on was within 24 hours of admission in 28% and a er stay of 7 days in NICU in 20%.The mean dura on of mechanical ven la on was 118 hours (Range 1-360 hours).
None of the neonates with RDS of prematurity survived.Survival rate was 25.3% in sepsis, 20% in MAS, 50% in birth asphyxia and 50% in apnea of prematurity group.Neonates with RDS of prematurity were started on bubble CPAP, and those who did not improve were administered surfactant as rescue therapy.Surfactant was expensive and not readily available.It was administered by INSURE technique following which neonates were kept under bubble CPAP.Only those who had persistent distress on bubble CPAP or developed some complica ons were mechanically ven lated 7,8,9 .In this study, 8 preterm neonates weighing 1250 -2250 grams (mean 1650 grams) of gesta on 26-34 weeks (mean 30 weeks) were administered surfactant.Out of eight, four needed mechanical ven la on soon a er administra on, later developed sepsis and died.The other four neonates improved on bubble CPAP a er surfactant administra on, but later during the course of hospital stay developed sepsis and required ven la on and subsequently succumbed.The causes of death were intraventricular hemorrhage (3), sep c shock (4), necro zing enterocoli s (1) and pulmonary hemorrhage (1).
Several co-morbid condi ons like sepsis, shock, acute kidney injury, disseminated intravascular coagula on, metabolic acidosis, dyselectrolytemia were seen.Table 3 demonstrates the occurrence of various complica ons and their associa on with outcome on univariate analysis.
Hospital acquired sepsis was a major complica on occurring in 47% pa ents on mechanical ven la on, manifested as ven lator associated pneumonia, meningi s, necro zing enterocoli s and sep c ileus.There were 16 blood culture posi ve cases whose an bio c sensi vity pa ern as shown in Table 5.There was an outbreak of Klebsiella pneumoniae, isolated in six pa ents.Only 18.7% of blood culture posi ve neonates survived.
Acute kidney injury was present in 24% of pa ents, associated with poor outcome (25%) although it was not sta s cally signifi cant.Two pa ents underwent peritoneal dialysis but both succumbed.Disseminated intravascular coagula on and pulmonary haemorrhage was present in 20% and 12% respec vely.Pneumothorax was present in four pa ents, one was associated with pneumomedias num before undergoing mechanical ven la on.

Discussion
The survival rate of neonates on mechanical ven la on in developing countries ranges from 25% to 64% 10,11,12,13,14,15 .In our study, one-third of admi ed neonates required mechanical ven la on and among them one-third survived (33.3%).Similar to data from other NICUs, in this study outcome was be er with increasing birth weight and gesta onal age 10,11,12,13,14,15 .Half of neonates in the study were preterm (51%).Survival rate was 33.3% for 34-37 weeks, 26.6% for 32-33 weeks and none survived below 31 weeks.
The most common indica on for ven la on was respiratory distress and sepsis.Similar pa ern was seen at Patan Hospital, Nepal with indica on being 33% HMD and 24% severe sepsis 14 .The commonest reason for ven la on described was respiratory distress(63%) in West Indies, birth asphyxia(60%) in Paropakar Maternity and Women's Hospital, Nepal and (34%)in BPKIHS, Nepal 10,13,15 .It was MAS in JIPMER 11 .
The disease pa ern in preterm were RDS of prematurity, apnea of prematurity, sepsis and in term were perinatal asphyxia, meconium aspira on syndrome and sepsis.In this study, survival was nil in RDS of prematurity.The poor outcome of neonates on MV for RDS of prematurity were limited use of surfactant, co-existence of co-morbidi es like shock, intracranial hemorrhage and occurrence of sepsis, necro zing enterocoli s, disseminated intravascular coagula on and pulmonary hemorrhage.Survival outcome of neonates on MV for RDS varied a lot and was reported to be 0% by Gurbacharya et al, 33.3% by Shah et al, 54% by Shrestha S et al from hospitals within the country.Use of surfactant was limited due to its cost and unavailability, similar to other centres in Nepal 13,14,15 .Outcome of neonates with RDS of prematurity was 82.6% in Kerala by Prabha et al and the authors a ributed the good outcome to universal use of surfactant 16 .In a study from West Indies, use of surfactant was 26% and there was no diff erence between neonates who received surfactant and who did not 10 .Survival of neonates with MAS was 20% in this study comparable to 25% in the study by Gurbacharya SM et al, but poorer that 60.7% in a series from JIPMER and 82% by Trotman 10,11,13 .Perinatal asphyxia cons tuted 11% of the mechanically ven lated neonates, among which survival rate was 50%.Non survivors included neonates with neurological defi cits who failed to improve despite treatment and/or were withdrawn from medical care by the parents.Studies show wide range of survival, 31.6% in Bangladesh, 68.2% in BPKIHS to 100 % in Kerala 12,14,16 .
Sepsis had a grave outcome.Survival was only 26.3%.Iqbal Q et al had survival of 35.3%, and Anantharaj A et al had 46.1% 11,17 .There was an outbreak of Klebsiella pneumoniae during the study period, and was responsible for increased incidence of sepsis and mortality.The organism was isolated in blood culture of 6 neonates, out of which only one survived.Most of these organisms were sensi ve to ciprofl oxacin, piperacillin-tazobactum and meropenem.However, two isolated were carbapenem-resistant strains.Similar outbreaks of Klebsiella in other NICUs were described with 64% mortality by Grey J et al at Guatemala 18 .Saleem AF et al described the increase in incidence of mul drug resistant Klebsiella pneumonia in NICU in Pakistan 19 .Sepsis was also a major issue in Patan Hospital NICU where it was the most common cause for need of mechanical ven la on as well as most common cause of mortality among admi ed neonates 14 .Kha ab A et al reported ven lator associated pneumonia in 55.2% neonates on mechanical ven la on 20 .
Sep c shock, DIC, pulmonary hemorrhage, acute kidney injury, necro zing enterocoli s, intraventricular hemorrhage and pneumothorax were associated with high mortality rates 21,22 .From a study in Kerala, shock was the commonest complica on with 73.8% survival.They also found that DIC and pulmonary hemorrhage were predic ve of mortality, the la er usually being a terminal event 16 .Riyas PK et al found complica ons in 58.8% neonates, including tube block (36%) and air leak (15%) 6 .Pneumothorax occurred in 4 neonates in this study, among which only one survived.Details of ven lator parameters and events during the course of ven la on like accidental extuba ons, re-intuba ons, risk factors for hospital acquired infec ons could not be collected which are our limita ons and further prospec ve studies are warranted.

Conclusions
One third of babies admi ed to NICU required mechanical ven la on and the most common indica on was severe respiratory distress.The disease pa ern in preterm were RDS of prematurity, apnea of prematurity, sepsis and in term were perinatal asphyxia, meconium aspira on syndrome and sepsis.The survival rate of ven lated neonates was 33.3%.The higher gesta onal age and birth weight was signifi cantly associated with be er outcome.Hospital acquired sepsis was a major complica on, resul ng in most of the deaths with mul -organ dysfunc on.The bacteria isolated were mul drug resistant.Eff ec ve measures for preven on and management of sepsis could improve the outcome of neonates in NICU.

Table 1 :
Profi le of ven lated neonates and rela on to mortality

Table 2 :
Indica ons for ini a on of mechanical ven la on

Table 3 :
Disease Pa ern of mechanically ven lated neonates and its outcome.

Table 4 :
Univariate analysis showing associa on of these parameters with mortality

Table 5 :
Sensi vity pa ern of organisms isolated in Blood culture