Analgesic effect of expressed breast milk in procedural pain in term neonates: a randomized, placebo-controlled, double-blind trial

AIM: To assess the effectiveness of expressed breast milk (EBM) in reducing pain due to venepuncture, in term neonates, as measured by behavioural and physiological observations. METHODS: This randomized, placebo-controlled, double-blind trial involved 81 full-term neonates, up to 4 wk of postnatal age, who needed venepuncture for blood investigations. Two minutes before the venepuncture, in the intervention arm, 40 babies received 5 ml of EBM, while 41 babies in control group received 5 ml of distilled water (DW) as placebo. Two observers who were blinded to the intervention recorded the physiological (heart rate and oxygen saturation) and behavioural parameters [duration of crying and modified Neonatal Facial Coding Scores (NFCS)] after the venepuncture. RESULTS: There was no difference in the baseline characteristics of the neonates in the two groups. The duration of crying was significantly shorter in babies fed EBM [median 38.5 s, interquartile range (IQR) 9.5-57.5 s] than in those fed DW (median 90 s, IQR 28-210 s). The mean duration of crying in EBM group was shorter by 70.7 (95% confidence interval 36.6-104.9) s. The modified NFCS at 0, 1 and 3 min was significantly lower (p < 0.01) in the EBM than in the DW group. The change in heart rate and oxygen saturation was significantly lower in the EBM group and returned to baseline values sooner than in the DW group. CONCLUSION: Feeding 5 ml of EBM before venepuncture is effective in reducing symptoms due to pain in term neonates.     

Analgesic effect of expressed breast milk in procedural pain in neonates

Prevention, treatment and assessment of neonatal pain have been of major clinical and scientific interest the last decades. Non-pharmacological interventions such as sweet oral solutions are successful in pain relief. Whether breast milk, with its lactose content of 7%, has any effect on the prevention of pain has been debated.

Conclusion: Randomized studies of breast milk in prevention and treatment of neonatal pain are needed.     

Midazolam sedation in mechanically ventilated newborns: a double blind randomized placebo controlled trial

OBJECTIVE: To determine efficacy of midazolam as a sedative in mechanically ventilated newborns. DESIGN: Double blind randomized placebo controlled trial. SETTING: Neonatal Unit of Tertiary Hospital. OUTCOME: Sedation over 48 h of observation. METHODS: Neonates with birth weight less than 2000 g who were mechanically ventilated within 7 days of life were randomly assigned to midazolam and placebo group. Midazolam and placebo were administered as bolus (0.2 mg/kg) followed by continuous infusion (0.06 mg/kg/h). Both groups received morphine infusion (10 microg/kg/h). Sedation score was noted at 6 hourly intervals for 48 hours. Hemodynamic variables, ventilatory variables, complications and side effects of treatments were also recorded. RESULTS: Thirty-three neonates were enrolled (17 in midazolam, 16 in placebo group). The groups were comparable for birth weights and gestation. The midazolam group had significantly better sedation from 18-24 hours after enrollment compared to placebo group. At 48 h there were no significant differences in proportion of infants with adequate sedation between midazolam and placebo group. The two groups were comparable with respect to heart rate, perfusion, ventilatory indices and blood gas parameters. None of the infants were noted to have hypotension on loading with midazolam or placebo. Seizures were noted in 2 neonates in placebo group 24 hours after enrollment (insignificant statistically). CONCLUSION: Sedation provided by continuous infusion of midazolam and morphine appears to be comparable to morphine alone in newborn babies on mechanical ventilation, with no significant adverse effects. The course of mechanical ventilation is not influenced by use of midazolam.     

Montelukast vs. inhaled low-dose budesonide as monotherapy in the treatment of mild persistent asthma: a randomized double blind controlled trial

BACKGROUND: Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma. Aim: To determine whether montelukast is as effective as budesonide in controlling mild persistent asthma as determined by FEV(1). METHODS: Between November 2003 to October 2005, participants aged 5-15 years with recently diagnosed mild persistent asthma (n = 62) were randomized to oral montelukast (5 mg daily) [N(1) = 30] or inhaled budesonide (400 microg per day in two doses) [N(2) = 32] in a single center, double-blind study. RESULTS: Baseline demographic and spirometric parameters were comparable. The median (95% confidence interval) percentage predicted FEV(1) was similar in the two groups after 12 weeks of treatment (budesonide: 76.70 (67.96-90.53%), montelukast: 75 (67.40-88.47)%; p = 0.44). There was similar improvement in spirometric parameters and clinical symptom scores in both the groups. There was no statistically significant difference between the groups in the need for rescue drugs as well as side effects reported by parents. CONCLUSION: Montelukast is as effective as inhaled budesonide in the treatment of mild persistent asthma in children aged 5-15 years. Montelukast may be used as an alternative to low dose inhaled corticosteroids for management of mild persistent asthma.     

Oral zinc supplementation for reducing mortality in probable neonatal sepsis: A double blind randomized placebo controlled trial

Objective

To study the role of Zinc in the treatment of neonatal sepsis.

Design

Double blind, randomized, placebo controlled trial.

Setting

Tertiary Care Hospital.

Participants

614 neonates with probable neonatal sepsis.

Intervention

The drug group (n=307) received 1mg/kg/day of elemental zinc, and placebo group (n=307) received the placebo, in addition to antibiotic therapy and supportive care, till the final outcome (discharge/death).

Outcome Measures

Decrease in mortality rates (primary outcome), duration of hospital stay and need of higher lines of antibiotic therapy (secondary outcomes) were tested.

Results

Baseline characteristics of the two groups were similar. No statistically significant differences between drug and placebo group were found in mortality rate (9.77% vs 7.81 %; P=0.393), mean duration of hospital stay (142.85±69.41 hrs, vs. 147.99±73.13 hrs; P=0.841), and requirement of higher lines of antibiotic therapy (13.35% vs 12.05%, P=0.628) after supplementation.

Conclusions

This study does not report decrease in mortality rates, duration of hospital stay and requirement of higher lines of antibiotic therapy following zinc supplementation in neonatal sepsis.     

Effect of kangaroo mother care Vs expressed breast milk administration on pain associated with removal of adhesive tape in very low birth weight neonates: A randomized controlled trial

Objective

To compare the pain relief effect of Kangaroo Mother Care (KMC) and Expressed Breast Milk (EBM) on the pain associated with adhesive tape removal in very low birth weight (VLBW) neonates.

Design

Randomized Controlled Trial.

Setting

Neonatal intensive care unit of a tertiary care teaching hospital.

Participants

15 VLBW neonates who needed adhesive tape removal for the first part and 50 VLBW neonates needing adhesive tape removal for the second part.

Methods

In first stage of the study, we studied whether adhesive tape removal in VLBW neonates was painful. In the second stage, eligible VLBW neonates were randomised to compare the efficacy of KMC and EBM in reducing the pain during the procedure of adhesive tape removal.

Outcome Variables

Premature Infant Pain Profile (PIPP) Score, heart rate, oxygen saturation.

Results

There was significant increase in pain associated with the removal of adhesive tape (Mean pre-procedure PIPP score 3.47 ± 0.74; post-procedure mean PIPP score 12.13 ± 2.59; P<0.0001). The post intervention mean PIPP pain score was not significantly different between the KMC and EBM groups (P= 0.62).

Conclusions

Removal of adhesive tape is a painful procedure for VLBW neonates. There was no difference between KMC and EBM in relieving pain associated with adhesive tape removal.     

How effective is tetracaine 4% gel,before a venipuncture,in reducing procedural pain in infants: a randomized double-blind placebo controlled trial

Background  

Procedural pain relief is sub-optimal in neonates. Topical tetracaine provides pain relief in children. Evidence of its efficacy and safety in neonates is limited. The objective of this study was to assess the efficacy and safety of topical tetracaine on the pain response of neonates during a venipuncture.     

Oral salbutamol for symptomatic relief in mild bronchiolitis a double blind randomized placebo controlled trial

OBJECTIVES: To determine the efficacy of oral salbutamol for providing symptomatic relief in mild bronchiolitis. DESIGN: Randomized double-blind placebo controlled trial. SETTING: Pediatric Outpatient Department of a tertiary care hospital. SUBJECTS: 140 infants (of 310 approached) with a clinical diagnosis of acute bronchiolitis. I N T E R V E N T I O N : Oral salbutamol (0.1 mg/kg/dose) (n=70) or placebo (n=70) three times a day for 7 days or till complete resolution of symptoms, whichever was earlier. OUTCOME VARIABLES: Time for resolution of illness (ROI), duration of fever, cough, coryza, noisy breathing, time to achieve normal feeding and normal sleep, and frequency of hospitalization and adverse effects. RESUltS: Median (SE, 95% CI) duration of resolution of overall illness was similar in the two groups [6 (0, 5 to 7) d in the salbutamol group vs. 5 (1, 4 to 6) days in placebo group; P=0.21]. There was no significant difference in mean duration of fever, cough, coryza, noisy breathing, time to achieve normal feeding and normal sleep; and frequency of hospitalization or adverse effects, between the two groups. However, tremors were observed in 5 infants in the salbutamol group. CONCLUSION: Oral salbutamol is not superior to placebo in reducing the duration of symptoms in mild cases of acute bronchiolitis in children.     

Effect of probiotics on allergic rhinitis in Df, Dp or dust-sensitive children: A randomized double blind controlled trial

Objective

To study, we examined the effect of Lactobacillus salivarius on the clinical symptoms and medication use among children with established allergic rhinitis (AR).

Design

Double blind, randomized, controlled trial.

Setting

Hualien Tzu-Chi General Hospital.

Methods

Atopic children with current allergic rhinitis received 4 × 10⁹ colony forming units/g of Lactobacillus salivarius (n=99) or placebo (n=100) daily as a powder mixed with food or water for 12 weeks. The SCORing Allergic rhinitis index (specific symptoms scores [SSS] and symptom medication scores [SMS]), which measures the extent and severity of AR, was assessed in each subject at each of the visits — 2 weeks prior to treatment initiation (visit 0), at the beginning of the treatment (visit 1), then at 4 (visit 2), 8 (visit 3) and 12 weeks (visit 4) after starting treatment. The WBC, RBC, platelet and, eosinophil counts as well as the IgE antibody levels of the individuals were evaluated before and after 3 months of treatment.

Results

The major outcome, indicating the efficacy of Lactobacillus salivarius treatment, was the reduction in rhinitis symptoms and drug scores. No significant statistical differences were found between baseline or 12 weeks in the probiotic and placebo groups for any immunological or blood cell variables.

Conclusions

Our study demonstrates that Lactobacillus salivarius treatment reduces rhinitis symptoms and drug usage in children with allergic rhinitis.     

Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants

BACKGROUND: Human milk has considerable short and long term benefits for preterm infants, but mothers may experience difficulties in expressing breast milk for infants too immature or sick to breast feed. Oxytocin has been used to assist breast feeding and milk expression, but few data are available to support this intervention in the neonatal unit setting. AIM: To test the hypothesis that oxytocin nasal spray increases early milk output in mothers expressing milk for preterm infants. METHODS: A randomised, double blind trial of oxytocin nasal spray (100 microl per dose) versus placebo was conducted in mothers delivering infants <35 weeks gestation. Sprays were used before expression of milk using an electric pump up to day 5. Main outcome: Total weight of milk expressed while using spray (study powered to detect >1SD difference between groups). Secondary outcomes: Pattern of milk production; number of pumping sessions; weight/fat content of milk expressed during a fixed 20 minute period on day 5 ("physiological study"); mother's opinion of expressing and spray assessed by questionnaire. RESULTS: Fifty one mothers were randomised (27 oxytocin, 24 placebo). Total milk production did not differ between groups. Repeated measures analysis of variance suggested significantly (p = 0.001) different patterns of milk production, with initial faster production in the oxytocin group then convergence between groups. Parity did not influence the response to the intervention. No significant differences were seen in milk weight or fat content in the physiological study nor in mothers' opinions of milk expression and treatment. CONCLUSIONS: Despite marginal differences in the pattern of early milk production, the use of oxytocin nasal spray did not significantly improve outcome. Most mothers believed they were receiving the active spray, suggesting a significant placebo effect (supported by limited data from historical controls) and benefits from the extra breast feeding support available during the study.     

Topical amethocaine gel for pain relief of heel prick blood sampling: a randomised double blind controlled trial

BACKGROUND: Heel prick blood sampling is a commonly performed and painful procedure in the newborn infant. Use of a topical local anaesthetic does not relieve this pain. A 4% w/w amethocaine gel (Ametop) reduces the pain of venepuncture in the newborn but has not been tried with heel pricks. AIM: To investigate the effect of topical amethocaine gel on the pain of heel prick in the newborn infant. DESIGN: Randomised, double blind, placebo controlled trial. SUBJECTS: Sixty newborn infants, gestation 28-42 weeks (median 36), postnatal age 1-16 days (median 5) undergoing routine heel prick blood sampling. METHODS: A 1.5 g portion of 4% w/w amethocaine gel or placebo was applied to the skin under occlusion for one hour, then wiped away. Heel prick blood sampling with a spring loaded lance was performed five minutes later. The procedure was videotaped and pain assessed at one second intervals using an adaptation of the neonatal facial coding system (NFCS). No or minimal pain was defined as a cumulative score of less than 5 (out of 15) in the three seconds after firing of the lance and as lack of a cry in the first five seconds. RESULTS: In terms of a low NFCS core and lack of cry (p = 0.12) 20 of 30 (67%) in the amethocaine group and 13 of 29 (45%) in the placebo group had no or minimal pain in response to the heel prick. The median cumulative NFCS score over the three seconds after firing the lance was 3 (interquartile range 0-6) in the amethocaine group compared with 5 (interquartile range 1-10) in the placebo group (p = 0.07). These differences are not significant. CONCLUSIONS: Topical amethocaine gel does not have a clinically important effect on the pain of heel prick blood sampling and its use for this purpose cannot therefore be recommended. Alternative approaches to the relief of pain from this procedure should be explored.     

Fenfluramine in Prader-Willi syndrome: a double blind,placebo controlled trial.

A double blind trial was conducted to determine the effect of fenfluramine on the weight and behaviour of patients with the Prader-Willi syndrome. Fifteen subjects, aged 5.5 to 27 years, received the placebo and the active drug, each for a period of six weeks. The dose of fenfluramine varied according to the age of the patient. Treatment with fenfluramine was associated with significant weight loss, improvement in food related behaviour, and a decrease in aggressive behaviour directed towards others. Skin picking and other self mutilation were unaffected by the drug. None of the subjects suffered from any side effects while taking the drug. These findings suggest that short term treatment with fenfluramine may have a role in the management of some patients with Prader-Willi syndrome. It could be used during periods when exposure to large amounts of food cannot be avoided and aggressive behaviour is particularly difficult to contain. It may also be useful in those whose lives are threatened by the complications of obesity.     

A randomized controlled trial of fluid supplementation in term neonates with severe hyperbilirubinemia

OBJECTIVE: To evaluate the effectiveness of fluid supplementation in decreasing the rate of exchange transfusion and the duration of phototherapy in term neonates with severe nonhemolytic hyperbilirubinemia. STUDY DESIGN: This was a randomized controlled trial conducted in a tertiary care referral unit in northern India. Seventy-four term neonates with severe nonhemolytic hyperbilirubinemia (total serum bilirubin > 18 mg/dL [308 micromol/L] to < 25 mg/dL [427 micromol/L]). The subjects were randomized to an "extra fluids" group (intravenous fluid supplementation for 8 hours and oral supplementation for the duration of phototherapy; n = 37) or a control group (n = 37). RESULTS: At inclusion, 54 infants (73%) had high serum osmolality, including 28 (75%) in the extra fluids group and 26 (70%) in the control group. The proportion of infants who underwent exchange transfusion was lower in the extra fluids group than in the control group: 6 (16%) versus 20 (54%)(P = .001; relative risk = 0.30; 95% confidence interval = 0.14 to 0.66). The duration of phototherapy was also shorter in the extra fluids group: 52 +/- 18 hours versus 73 +/- 31 hours (P = .004). CONCLUSION: Fluid supplementation in term neonates presenting with severe hyperbilirubinemia decreased the rate of exchange transfusion and duration of phototherapy.