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80 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3 Sep. 30 2012 臨 床 藥 物 治 療 學 Therapeutics of Clinical Drugs LBW Neonates Requiring Short-Term PN Tend to Prolong ICU Stay Peng-Hsiung Wang 1 , Zon-Min Lee 1 , Ping-Yu Lee 1 Chi-Wen Chiang 2 Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital 1 Department of Pharmacy, Pingtung Hospital, Department of Health, Executive Yuan, Pingtung 2 Abstract Background: High risk neonates hospitalized for surgical or cardiac complications, extremely premature neonates, or those with protracted diarrhea pose a particular nutrition support challenge. Low birth weight (LBW) neonates who need prolonged parenteral nutrition (PN) supplements are supposed to stay in the neonatal intensive care unit (NICU) for longer time due to severe underlying diseases or immature physical condition. However, there was few published literature described the relationship between short-term (5 days) PN use for neonates and length of NICU stay. Methods: The charts of all neonates weighing between 1.5 and 2.5 kg upon admission to our NICU from Jan. 2010 through Apr. 2011 were studied. In total 184 LBW neonates have entered into this study. Results: Their birth weights range from 1505 to 2490 g (2030.9±270 g). Seven out of 184 neonates used long-term (>5 days) PN, 10 neonates used short-term PN and the other 167 neonates did not. The average lengths of NICU stay of long-term, short-term PN users and non-users are 52.9±52.7, 27.6±11.7 and 15.5±8.5 days, respectively. Significant difference of length of NICU stay was observed not only in the long-term users but also between short-term PN users and non-users, P<0.001 (t-test), suggesting that malnutrition requiring short-term (5 days) PN use has an inuential impact on the length of neonatal

LBW Neonates Requiring Short-Term PN Tend to Prolong … · LBW Neonates Requiring Short-Term PN Tend to Prolong ICU Stay ... infants have a low tolerance to enteral feeding, they

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80 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3 Sep. 30 2012

臨 床 藥 物 治 療 學 Therapeutics of Clinical Drugs

LBW Neonates Requiring Short-Term PN Tend to Prolong ICU Stay

Peng-Hsiung Wang1 , Zon-Min Lee1, Ping-Yu Lee1

Chi-Wen Chiang2

Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital1

Department of Pharmacy, Pingtung Hospital, Department of Health, Executive Yuan, Pingtung2

Abstract

Background: High risk neonates hospitalized for surgical or cardiac complications,

extremely premature neonates, or those with protracted diarrhea pose a particular nutrition

support challenge. Low birth weight (LBW) neonates who need prolonged parenteral

nutrition (PN) supplements are supposed to stay in the neonatal intensive care unit (NICU)

for longer time due to severe underlying diseases or immature physical condition. However,

there was few published literature described the relationship between short-term (≤ 5 days)

PN use for neonates and length of NICU stay.

Methods: The charts of all neonates weighing between 1.5 and 2.5 kg upon admission

to our NICU from Jan. 2010 through Apr. 2011 were studied. In total 184 LBW neonates

have entered into this study.

Results: Their birth weights range from 1505 to 2490 g (2030.9±270 g). Seven out of

184 neonates used long-term (>5 days) PN, 10 neonates used short-term PN and the other

167 neonates did not. The average lengths of NICU stay of long-term, short-term PN users

and non-users are 52.9±52.7, 27.6±11.7 and 15.5±8.5 days, respectively. Significant

difference of length of NICU stay was observed not only in the long-term users but also

between short-term PN users and non-users, P<0.001 (t-test), suggesting that malnutrition

requiring short-term (≤ 5 days) PN use has an influential impact on the length of neonatal

第28卷第3期Sep. 30 2012

LBW Neonates Requiring Short-Term PN Tend to Prolong ICU Stay

藥學雜誌 第112冊 81

Introduction

High risk neonates hospitalized for surgical or cardiac complications, extremely premature neonates, or those with protracted diarrhea pose a particular nutrition support challenge.1 Postnatal growth deficit is the most commonly observed morbidity in very low birthweight infants and is due, at least in part, to inadequate early nutritional intake during hospitalization.2 In addition, neonates born at less than 37 weeks' gestation also have significantly increased fasting (NPO) days and longer length of stay when compared with neonates born at greater than 37 weeks.3

During their first weeks of life, very premature infants are at high risk of disturbed glucose homeostasis, which might result in increased morbidity and mortality. As these infants have a low tolerance to enteral feeding, they usually depend on parenteral nutrition (PN).4 Neonates with short gut or bowel atresia also have a long duration of PN 5 which offers the possibility of increasing or ensuring nutrient intake in patients in whom normal food intake is inadequate, enteral nutrition is not feasible or contraindicated.6 PN, a key therapeutic option in neonates whose clinical conditions require a period of bowel rest, is indicated as a lifesaving

therapy in those with intestinal failure from

any of several causes, including necrotizing

enterocolitis, intestinal atresia, pseudo-

obstruction, and other motility disorders,7 that

is, early nutrition is associated with marked

long-term benefits for certain premature

neonates.8

In some situation, LBW neonates (birth

weight <=2500 g) require PN to help achieve

adequate nutrition intakes for growth and

development. LBW neonates who need prolonged

PN supplements are supposed to stay in the

NICU for longer time due to severe underlying

diseases or immature physical condition.

However, there was few published literature

described the relationship between short-term (≤5

days) PN use for neonates and length of NICU

stay, that's why this study has been undertaken

to find out whether length of NICU stay of LBW

neonates receiving short-term PN is longer than

those who didn't due to malnutrition.

Methods

A re t rospec t ive cha r t r ev iew was

conducted, and neonates weighing between

1.5 and 2.5 kg upon admission to our NICU

from Jan. 2010 through Apr. 2011 were studied.

Neonates born in other hospitals and sent to

ICU stay.

Conclusion: LBW neonates are vulnerable to malnutrition-early evaluation of nutrition

situation and use of PN if needed might be essential for this group of patients.

Key words: LBW neonate, PN, ICU stay

82 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3 Sep. 30 2012

臨 床 藥 物 治 療 學 Therapeutics of Clinical Drugs

our NICU over 24 hours after birth were not

enrolled due to incomplete data. Exclusion

criteria were: those expired or those born with

gastroschisis, tracheoesophageal fistula, and

congenital diaphragmatic hernia. In total 184

LBW neonates of those admitted to this NICU

have entered into this study. Definition of days

of PN use is the use of parenteral nutrition for

more than one hour a day.

Statistical analysis: the results are given

as means with standard deviations. Independent

T-test was chosen to compare the differences

of Apgar scores, birth weights and gestational

weeks between these two groups. Statistical

significance was defined as a value <0.05.

In this NICU, PN is provided to neonates

who cann't be fed orally or enterally, and

minimal caloric requirements of 80 kcal/kg/

day or protein intake of 2 g/kg/day can not be

reached. All pediatricians use this similar rule

for neonatal nutrition. Pediatricians making the

decisions to use or delete PN, or to transfer a

neonate to a common neonatal ward were not

involved in the study, and the other members

were blinded with respect to group.

Results

In total 184 LBW neonates of those

admitted to this NICU have entered into this

study. Their birth weights range from 1505

to 2490 g (2030.9±270 g). Seven out of 184

neonates used long-term (>5 days) PN, 10

neonates used short-term (≤5 days) PN and

the other 167 neonates did not. The average

Apgar scores, birth weights and gestational

weeks of LBW neonates of short-term PN users

versus non-users are 6.05±0.76: 5.84±0.59

(p=0.29), 1878.3±226.7 g: 2051.4±266.5 g

(p=0.046), 32.4±2.5weeks: 31.1±2.2weeks

(p=0.28), respectively. RDS (respiratory

distress syndrome) rates at birth of both groups,

regardless of using surfactant or not, are 0.300

(3/10 neonates): 0.299 (50/167 neonates), no

significant difference.

The average lengths of NICU stay of long-

term, short-term PN users and non-users are

52.9±52.7, 27.6±11.7 and 15.5±8.5 days,

respectively. Significant difference of length of

NICU stay was observed not only in the group

of long-term users but also between short-

term PN users and non-users, P<0.001(t-test),

suggesting that malnutrition requiring short-

term (≤5 days) PN use has an influential impact

on the length of neonatal ICU stay.

Discussion

RDS rates at birth are used to evaluate the

contributing factor leading to the development

of bronchopulmonary dysplasia, a major cause

of increased length of hospitalization,9 and

results show no significant difference between

these two groups.

APGAR (Appearance, Pulse, Grimace,

Activity, and Respiration) is a score to measure

the health situation of a neonate within minutes

after birth. The higher the score, the healthier

a neonate is considered; scores ranging from 0

to 10. 0-3: critically ill, 4 to 6: less satisfying

and 7 to 10: generally normal. Besides Apgar

score, birth weights, and gestational weeks are

also compared between these two groups, and

results show the basis for comparison is roughly

第28卷第3期Sep. 30 2012

LBW Neonates Requiring Short-Term PN Tend to Prolong ICU Stay

藥學雜誌 第112冊 83

equal (p=0.29 for Apgar scor, and p=0.28 for gestational weeks) except for birth weights (p=0.046). Results show no conclusive equal background but similarity, and due to significant difference of length of NICU stay was observed between these two groups (P<0.001, t-test), that is why "tend to" is used in the title. Further studies with more neonates included are needed to have definitive conclusion.

In this NICU, neonates qualified to be transferred to a common neonatal ward are those who do not have any signs of infections, whose body weight is over 2000 g, those that are comfortable without the use of an oxygen hood or ventilator, and those with smooth feeding. Therefore, being able to be transferred to a common ward is equal to be generally healthy in this study so as to provide a relatively equal basis for comparison among LBW neonates.

LBW neonates require protein and energy for their growth,10 and the early provis ion of nut r ients i s an impor tant determinant of postnatal growth.11 Use of PN may be associated with some problems, like precipitates during the administration of PN,10 liver dysfunction,12 infectious and metabolic complication,7 etc. However, neither precipitates since the use of inline filters nor infections due to malpractice of preparing PN solutions have occurred in this NICU in recent years, and liver dysfunction or fluctuation of sugar levels which are usually seen in long-term PN users is not significant in short-term PN users.12,13 Also, the short-term PN in critically ill patients does not exert a different influence

on the serum concentrations of GI hormones compared to enteral nutrition,13 and no specific side effects were detected in this group of patients in former studies,14 suggesting that short-term PN use is feasible and appropriate for certain neonates.

PN offers the possibility of increasing or ensuring nutrient intake in patients in whom normal food intake or enteral nutrition is not feasible,6 and its initial goal is to provide sufficient nutrients to prevent negative energy and nitrogen balance and essential fatty acid deficiency. The average starting day of use of short-term PN is 3-4 days after birth in this NICU which is contradictory to some studies,15 i.e. they might have had a better outcome and discharged earlier if these neonates received PN earlier. Consequently, not only those suffering from malnutrition requiring long-term PN supplements are supposed to stay in the NICU for longer time due to severe underlying diseases or immature physical condition, but also these receiving short-term (≤5 days) PN. Therefore, how to manage to evaluate LBW neonates' nutrition situation within days after birth is essential for their health, and possibly shorten lengths of their NICU stay and reduce medical costs.

In total 17 LBW neonates born in other hospitals and sent to this NICU over 24 hours after birth were not enrolled due to incomplete data in this study. The reason why those born with gastroschisis, tracheoesophageal fistula, and congenital diaphragmatic hernia were excluded from this study is that it's obvious LBW neonates with any of these diseases stay

84 THE JOURNAL OF TAIWAN PHARMACY Vol.28 No.3 Sep. 30 2012

臨 床 藥 物 治 療 學 Therapeutics of Clinical Drugs

longer in the NICU, and only three had the

situations and were excluded during the study

period.

PN solutions for neonates within days

after birth vary in constituents. For example,

no potassium is supposed to be added to a PN

solution until after first urination for fear of

hyperkalemia. In addition, calcium intake for

a neonate is about 5 to 15 times higher than

for an adult on the basis of body weight due

to the increase in calcium demand to support

the rapid growing skeleton. Moreover, amino

acids requirements are also different in volume

as well as varieties (rich in leucine, isoleucine

and valine). Therefore, a customized PN

solution is essential for an individual neonate's

requirements.

Conclusion

PN is commonly used in the NICU for

nutritional support of preterm neonates. LBW

neonates are vulnerable to malnutrition and the

age at which neonates first receive PN or are

fed enteral feeds appear to influence their health

and the length of NICU stay-early evaluation

of nutrition situation and use of PN if needed

might be essential for this group of patients.

References:

1. Christina JV, Teresa DP: Enhancing Parenteral Nutrition Therapy for the Neonate. Nutrition in Clinical Practice 2007; 22: 183-193.

2. Eleni-dit TS, Kermorvant DE, Huon C, et al: Early in-dividualised parenteral nutrition for preterm infants. Archives of Disease in Childhood Fetal and Neonatal Edi-tion 2009; 94(2): 152-153.

3. Puligandla PS, Janvier A, Flageole H, et al: The signifi-cance of intrauterine growth restriction is different from prematurity for the outcome of infants with gastroschisis. Journal of Pediatric Surgery 2004; 39(8): 1200-1204.

4. Chacko SK, Sunehag AL: Gluconeogenesis continues in

premature infants receiving total parenteral nutrition. Ar-chives of Disease in Childhood: Fetal and Neonatal Edi-tion 2010; 95(6): 413-418.

5. Tawil KA, Gillam GL: Gastroschisis: 13 years' experience at RCH Melbourne. Journal of Paediatrics & Child Health 1995; 31(6): 553-556.

6. Bozzetti F, Arends J, Lundholm K, et al: ESPEN Guide-lines on Parenteral Nutrition: non-surgical oncology. Clinical Nutrition 2009; 28(4): 445-454.

7. Pianese P, Salvia G, Campanozzi A, et al: Sterol Profiling in Red Blood Cell Membranes and Plasma of Newborns Receiving Total Parenteral Nutrition. Journal of Pediatric Gastroenterology and Nutrition 2008; 47(5): 645-651.

8. Khashu M, Harrison A, Lalari V, et al: Impact of shielding parenteral nutrition from light on routine monitoring of blood glucose and triglyceride levels in preterm neonates. Archives of Disease in Childhood Fetal and Neonatal Edi-tion 2009; 94(2): 111-115.

9. Zon-Min L, Chiu-Ying W, Chi-Wen C, et al: Patent Duc-tus Arteriosus might be a contributing factor affecting on Length of ICU Stay of VLBW Neonates. The Journal of Taiwan Pharmacy 2010; 26(4): 3-8.

10. Chaieb SD, Chaumeil JC, Jebnoun S, et al: Effect of high calcium and phosphate concentrations on the physico-chemical properties of two lipid emulsions used as total parenteral nutrition for neonates. Pda Journal of Pharma-ceutical Science&Technology 2009; 63(1): 27-41.

11. Martin CR, Brown YF, Ehrenkranz RA, et al: Nutritional practices and growth velocity in the first month of life in extremely premature injfants. Pediatrics 2009; 124(2): 649-657.

12. Moreno Villares JM, Gomis Munoz P, Galiano Segovia MJ, et al: Liver complications associated with short-term parenteral nutrition in children. Anales Espanoles de pe-diatria 1999; 51(1): 22-26.

13. Mandragos C, Moukas M, Amygdalou A, et al: Gastroin-testinal hormones and short-term nutritional schedules in critically ill patients. Hepato-Gastroenterology 2003; 50 (53): 1442-1445.

14. Prinzler HJ, Weidler B, Lohmann B, et al: Routine post-operative parenteral feeding with a complete solution. Infusionstherapie (Basel) 1990; 17(2): 84-88.

15. Monroy TR, Macias AE, Ponce-de LS, et al: Weight gain and metabolic complications in preterm infants with nu-tritional support. Revista de Investigacion Clinica 2011; 63(3): 244-252.

摘要

需短期靜脈營養的低出生體重新生兒可

能需住加護病房較久

背景:高風險新生兒因接受手術治療,

或因心臟併發症、極度早產、長時間拉肚子

等來住院均會造成營養需求的挑戰。需長期

使用靜脈營養 (PN) 的低出生體重 (LBW) 新

第28卷第3期Sep. 30 2012

LBW Neonates Requiring Short-Term PN Tend to Prolong ICU Stay

藥學雜誌 第112冊 85

生兒常常會因有潛在疾病或不成熟的生理狀

況,而需在新生兒加護病房 (NICU) 住較久的時間。然而,幾乎沒有已發表的文獻曾經

探討使用短期 (≤5天) PN 與新生兒住 NICU 時間長短的相關性。

方法:於2010年1月至2011年4月所有住進我們 NICU 的新生兒,其體重介於1.5至2.5公斤的病歷都被查閱。此期間總共有184位 LBW 新生兒納入本研究。

結果:他們的出生體重範圍1505至2490克 (2030.9±270克)。此184個新生兒中有7名使用長期 (>5天) PN, 10名使用短期而其他167名不曾使用。此長期使用 PN、短期使用與不曾使用新生兒之平均住 NICU 天數分別為52.9± 52.7,27.6± 11.7 及15.5± 8.5

天。不僅是長期使用 PN 新生兒的住 NICU 天數有顯著差別於其它兩組,連短期使用與

不曾使用PN新生兒間也出現有意義的差別, P<0.001 (t-test),意指營養不良到需使用短期 PN 支持對 NICU 住院天數是有影響的。

結論:LBW 新生兒的健康情形是很容易受到營養不良所影響-及早做新生兒的營養狀況評估和對有營養不良之新生兒及早使

用 PN 或許是有利的。

作者

高雄長庚紀念醫院藥劑部藥師 王鵬翔、 李榮明、李炳鈺

行政院衛生署屏東醫院藥劑科藥師 江吉文