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Glycerin laxatives are often prescribed in the neonatal population for meconium evacuation and to promote enteral feeding. However, the literature regarding their effectiveness has not been systematically reviewed.
To assess the effectiveness of glycerin enema or suppository in preventing feeding intolerance in preterm infants at ≤32 weeks’ gestational age or weighing ≤1500 g at birth.
The Medline, Embase, Cochrane Library, Scopus and Web of Science databases were searched to identify studies that evaluated glycerin enemas/suppositories for feeding intolerance. Using the Evidence Evaluation Worksheet adapted from the American Heart Association’s International Liaison Committee on Resuscitation, eligible studies were scored for quality, level of evidence and direction of support.
Two clinical studies that evaluated meconium evacuation and feeding intolerance were included. One study showed no difference in the time to complete meconium evacuation or establishment of full enteral feeds, while the other showed that the times to first meconium passage and full enteral feeding were significantly shorter, and the rate of sepsis was lower in the glycerin enema group.
The evidence regarding the effectiveness of glycerin laxatives for improving feeding tolerance is inconclusive in infants at ≤32 weeks’ gestational age or weighing ≤1500 g at birth.
Les laxatifs à la glycérine sont souvent prescrits à la population néonatale afin de favoriser l’évacuation de méconium et de promouvoir l’alimentation entérale. Cependant, les publications portant sur leur efficacité n’ont pas fait l’objet d’analyse systématique.
Évaluer l’efficacité d’un lavement ou d’un suppositoire à la glycérine pour prévenir l’intolérance à l’alimentation chez les prématurés d’un maximum de 32 semaines d’âge gestationnel ou d’un maximum de 1 500 g à la naissance.
Les auteurs ont fait des recherches dans les bases de données de Medline, d’Embase, de la bibliothèque Cochrane, de Scopus et de Web of Science afin de trouver des études qui portaient sur les lavements ou les suppositoires à la glycérine pour prévenir l’intolérance à l’alimentation. Au moyen de l’Evidence Evaluation Worksheet adaptée de l’International Liaison Committee on Resuscitation de l’American Heart Association, les auteurs ont attribué une note aux études admissibles à l’égard de leur qualité, de la qualité des preuves et de l’orientation du soutien.
Deux études cliniques qui portaient sur l’évacuation du méconium et l’intolérance à l’alimentation ont fait partie de l’analyse. L’une n’a révélé aucune différence dans le délai pour terminer l’évacuation de méconium ou établir une alimentation entérale complète, tandis que l’autre a établi que le délai avant le premier passage de méconium et l’alimentation entérale complète était considérablement plus court et le taux de septicémie plus faible dans le groupe ayant subi un lavement à la glycérine.
Les données probantes relatives à l’efficacité des laxatifs à la glycérine pour améliorer la tolérance à l’alimentation ne sont pas concluantes chez les enfants d’un maximum de 32 semaines d’âge gestationnel ou d’un maximum de 1 500 g à la naissance.
Feeding intolerance, a common problem in preterm infants, usually manifests with the presence of residual feeds/aspirates before the next scheduled feeding, bilious aspirates, abdominal distension, emesis or lack of stooling (1,2). In such situations, clinical management includes discontinuation of enteral feeds and administration of total parenteral nutrition (TPN). The detrimental effects of prolonged administration of TPN include sepsis, TPN-related cholestasis and hepatic dysfunction, longer hospital stays and higher costs to the health care system (3–5). Therefore, strategies (1) to promote feeding tolerance and to prevent necrotizing enterocolitis (NEC) have been used, such as the administration of antenatal steroids (6–8), exclusive use of breast milk (9–12), early initiation of enteral feeds, mode of administration of feeds (continuous versus bolus feeds) and use of probiotic and prokinetic agents. In addition, glycerin laxatives (enema or suppositories) have been used to encourage the passage of meconium, decrease gastrointestinal transit time and improve feeding tolerance. Glycerin laxatives stimulate evacuation by being an osmotic dehydrating agent and increasing osmotic pressure in the gut.
We reviewed the literature to evaluate the effectiveness of pro-phylactic glycerin enema or suppository in preventing feeding intolerance in preterm infants of ≤32 weeks’ gestational age (GA) or having a birthweight (BW) of ≤1500 g.
Key words selected with synonyms were “Glycerin enema” OR “suppository” OR “glycerol” and “neonate” OR “newborn” OR “pre-term” OR “infan*” These concepts were combined with the Boolean operator “AND”. Animal subjects, abstracts only and children/adult subjects were excluded. No language restrictions were applied.
The following databases were searched: Ovid Medline (1950 to 2010), Scopus (1997 to March 9, 2011), Web of Science (1997 to March 9, 2011), Embase (1987 to March 9, 2011), CINAHL (1982 to March 9, 2011), Central Register of Controlled Trials Cochrane 1st Quarter 2011 and Cochrane Database of Systematic Reviews 1st Quarter 2011. The bibliographies of all selected articles and several review articles were manually searched for additional studies.
Of the 112 articles reviewed, four studies were excluded because feeding intolerance was not an outcome. Two studies were eligible for inclusion and were scored using the Evidence Evaluation Worksheet adapted from the American Heart Association’s International Liaison Committee on Resuscitation (13) by two authors (VS, NC) for level of evidence, direction of support and quality. Discrepancies were resolved through consensus with the third author (SL).
Two clinical studies were included: a randomized controlled trial (RCT) (n=1) (14), and an observational cohort study (n=1) (15). Study characteristics and the level of evidence is presented in Table 1.
Haiden et al (14) evaluated the effectiveness of glycerin enema compared with no intervention in accelerating meconium passage and promoting feeding tolerance in 81 infants with BW ≤1500 g and GA ≤32 weeks. Infants who failed to spontaneously pass meconium in the first 12 h of life were randomly assigned to receive glycerin enema (10 mL/kg saline containing 0.8 g/10 mL glycerin) or no intervention. A urinary catheter (Ch 8) lubricated with petrolatum was inserted into the rectum (2 cm in infants <1000 g and 3 cm in infants weighing between 1000 g and 2000 g) to administer the enema. A second enema was administered if the infant failed to pass meconium during the 24 h following the enema. The procedure was repeated until complete evacuation of meconium was achieved (defined as passage of two stools without macroscopic evidence of meconium within 24 h). The time to complete evacuation of meconium was defined as the time when the first meconium-free stool was passed. Oral feedings were started in both groups – the earliest after 12 h of life and after the first meconium passage. Full enteral feeds were defined as an oral intake of 150 mL/kg/day. The median time to complete evacuation was not different between the intervention compared with the no intervention group (6.5 days [95% CI 6 to 9.6 days] versus nine days [95% CI 7.7 to 11 days]; P>0.05). Similarly, the median time to achieve full enteral feedings was not different between the groups (26 days [range eight to 83 days] versus 27 [range five to 75 days]; P=0.65).
In an observational study, Shim et al (15) evaluated the effect of early meconium evacuation on feeding tolerance in infants with a BW <1500 g and who were fed only human milk by reviewing the health records between January 2003 and December 2005. In their unit, from January 1, 2003, to August 30, 2004 (n=44 infants), conventional methods such as rectal stimulation (performed two to three days after no meconium passage) followed by glycerin enema in case of meconium passage failure were used. Between September 1, 2004, and December 31, 2005 (n=39 infants), routine glycerin enema (1 mL/kg every 12 h to 24 h within 24 h after birth until meconium passage was complete) was administered. The glycerin solution was diluted 1:4 with distilled water, and instilled into the rectum using a 5F nelaton catheter cut to 3 cm and connected to the enema-filled syringe. The tip of the catheter was placed 0.5 cm above the anus. In all infants, stool occult blood test was performed once a day. The primary outcome was the time to reach full enteral feeds, which was defined as a volume of >100 mL/kg/day. Of the 83 infants enrolled, 13 were excluded due to the inability to establish initial enteral feeding before two weeks of age due to patent ductus arteriosus ligation (n=4) or early sepsis and disseminated intravascular coagulopathy (n=5), surgery due to ileal atresia or perforation secondary to NEC (n=3) and congenital malformation (n=1). Infants achieved full enteral feeds earlier in the intervention group compared with the control group (median 16 versus 22.9 days; P<0.001). Furthermore, this difference was larger for infants with BW <1000 g (median 17.3 versus 28.1 days; P<0.001). Infants in the intervention group passed the first meconium earlier than the control group (median 1.4 days versus 3.7 days; P<0.001). Sepsis was less frequent in the intervention versus the control group (7.7% versus 27.8%; P=0.02). Even though the incidence of NEC was less frequent in the intervention group, the difference was not statistically significant (2.6% versus 13.6%; P=0.11). One infant had rectal bleeding and two infants had occult bleeding in the intervention group.
The study by Haiden et al (14) was a good-quality RCT. However, protocol violation occurred in 23 infants (15 in the intervention group did not receive enema, while eight infants in the control group received enemas). Both intention-to-treat and per-protocol analyses were performed with no influence on the conclusion.
The study by Shim et al (15) was an observational cohort study of fair quality. Using a preintervention and postintervention study design, the authors demonstrated a significant effect on feeding intolerance and sepsis prevention.
It is recognized that the presence of food in the gastrointestinal tract is important for its structural and functional integrity (16–19). Furthermore, there is evidence to suggest that a delay in establishing full enteral feeds is associated with poor short- and long-term neonatal outcomes (20).
Recently, meconium retention has been recognized as a cause of bowel dysfunction in low BW infants (21,22). Unlike most term infants who pass meconium within the first 48 h, significant delay is observed in preterm infants. Loening-Baucke and Kimura (23) reported that only 37% of preterm infants passed stool in the first 24 h, while delay beyond 48 h was observed in 32%. Meetze et al (24) reported that the median (range) age of meconium passage in very low BW infants was 43 h (0.5 h to 27 days). In addition, total meconium evacuation (passage of the last meconium) may have a close relationship with feeding volume on day 14 of life (25). Glycerin suppositories are, therefore, commonly used in neonatal intensive care units to stimulate meconium passage and improve feeding tolerance.
Of the two eligible studies included in the present review, one was neutral (14), while the other was supportive (15). Although both studies had comparable BWs and GAs, there were differences in the volume of enema, type of enteral feeds and the definition of full enteral feeds used in the two eligible studies. Haiden et al (14) administered a volume of 10 mL/kg with glycerin diluted in saline, while Shim et al (15) used a dose of 1 mL/kg with glycerin diluted in distilled water. Haiden et al (14) hypothesized that the volume of enema might influence the ability to mobilize meconium from the colon and small bowel and improve feeding tolerance; this was disproved by Shim et al (15). Infants in the study by Shim et al (15) received human milk, while Haiden et al (14) allowed the use of breast milk, diluted hydrolyzed whey-dominated milk protein or premature infant formula for enteral feeds. In the study by Shim et al (15), full enteral feeds was defined as tolerating a volume of >100 mL/kg/day, while Haiden et al (14) used a volume of 150 mL/kg/day. Even though these differences may have influenced the conclusion, the data are limited to make a recommendation on the use of glycerin laxatives in clinical practice.
One RCT with a small sample size showed no benefit from the use of glycerin laxatives, while an observational study did demonstrate benefit in terms of time to achieve full feeds and reduction in sepsis rate.
The evidence regarding the effectiveness of glycerin laxatives for improving feeding tolerance in very low BW infants is inconclusive.
The authors thank Elizabeth Uleryk at the Hospital for Sick Children, Toronto, Ontario, for her contribution in developing and running the search strategy.
EPIQ STUDY PI: Dr Shoo K Lee, Mount Sinai Hospital, Toronto, Ontario. EPIQ Evidence Review Group: Chair: Dr Nalini Singhal, Foothills Medical Centre, Calgary, Alberta. Members: Dr Kim Dow, Kingston General Hospital, Kingston, Ontario; Dr. Andrew James, Hospital for Sick Kids, Toronto; Dr Ibrahim Mohamed, Hospital Sainte-Justine, Montreal, Quebec; Dr Nicole Rouvinez-Bouali, Children’s Hospital of Eastern Ontario, Ottawa, Ontario; Dr Koravangattu Sankaran, Royal University Hospital, Saskatoon, Saskatchewan; Dr Vibhuti Shah, Mount Sinai Hospital, Toronto; Dr Wendy Yee, Foothills Medical Centre, Calgary.