Methaemoglobinaemia risk factors with inhaled nitric oxide therapy in newborn infants

Background: Inhaled nitric oxide (iNO), commonly used for hypoxic neonates, may react with haemoglobin to form methaemoglobin (MetHb). MetHb monitoring during iNO therapy has been questioned since low doses of iNO are used. Aim: To evaluate the incidence of and identify risk factors associated with elevated MetHb in neonates treated with iNO. Methods: Neonates who were treated with iNO and had at least one MetHb measurement were included. Demographic characteristics and methods of iNO administration (dosage, duration) at the time of each MetHb measurement were analysed. Results: Four hundred and fifty‐two MetHb measurements from 81 premature and 82 term and near‐term infants were analysed. MetHb was above 5% in one‐term infant, and between 2.5–5% in 16 infants. A higher maximum dose of iNO (22.7 vs 17.7 p.p.m.), but not gestational age, was a significant risk factor for elevated MetHb. Significantly higher oxygen levels (75.5% vs 51.7%) were associated with higher MetHb in term infants. Preterm infants had no risk for high MetHb when iNO was kept below 8 p.p.m. These data suggest the possibility of limiting blood withdrawal when low doses iNO are used. Conclusion: High MetHb is exceptional in neonates treated with low dose iNO. Associated risk factors are related to high iNO dose and the simultaneous use of high concentrations of oxygen.     

Methaemoglobinaemia among neonates in a neonatal intensive care unit

After detection of a few clinical cases of methaemoglobinaemia (methb) in our NICU, a prospective clinical study was undertaken to determine the extent of the problem and to identify the causes. Consequently, during the following 8 months all haemoglobin tests included simultaneous measurements of methb on an OSM 3 hemoximeter (Radiometer): 8% (n= 33) of 415 neonates were found to be methb positive (denned as ≥6% methb). Mean methb was 19% (range 6.5–45.5%). Maximum methb concentrations were found on day 4–31 postpartum (mean 12 days) and the number of days with a positive methb sample ranged from 1 to 18 days (mean 6 days). About 40% of the neonates born at 25–30 weeks of gestation and 60%) with a birth weight < 1000 g were methb positive. Also, there was a negative correlation between the size of the methb positive concentration and gestational age (r=– 0.38,p= 0.02). Measurements of C–reactive protein and leucocytes, NADH reductase, pH, CI, nitrate and nitrite were carried out in methb positive patients. The tests were repeated 1 week after cessation of methb. The only significant difference was an increase in NADH reductase at the second measurement. Likewise, a wide range of clinical parameters were registered and they occurred with a higher frequency among the methb positive patients when compared with a methb negative control group matched with regard to gestational age and the closest possible birth weight. The mean birth weight of methb positive patients was 1170g and that of negative controls 1380g (p < 0.006). Epidemiological data and intervention studies indicated that para–chloraniline was the direct cause of the epidemic. The substance was derived from 0.02% chlorhexidine being inadvertently added to the humidifying fluid of the new incubators. Treatment of severe methb in premature neonates with 0.3–1.0mg methylene blue/kg body weight proved efficient. In conclusion, premature neonates developed severe methb when exposed to even small amounts of para–chloraniline. Immaturity, severe illness, the time exposed to para–chloraniline and low concentrations of NADH reductase probably played a part while other well known factors such as increased nitrite and nitrate concentrations, acidosis and hyperchloraemia did not seem to be significant.     

Methaemoglobinaemia with G6PD deficiency: rare cause of persistently low saturations in neonates

We report a very rare case of methaemoglobinaemia associated with glucose 6 phosphate dehydrogenase (G6PD) deficiency, complicating a respiratory illness in a preterm neonate. This neonate had consistently low saturation readings despite being ventilated at moderately high pressures in 100% oxygen. An arterial blood gas confirmed a high methaemoglobin level and a high pO2, inconsistent with the saturations. In addition, the bilirubin increased to exchange levels and was difficult to control with quadruple phototherapy. A double volume exchange transfusion was performed, which reduced both bilirubin and methaemoglobin. The pulse oximetry then started to correlate well with pO2. G6PD deficiency was confirmed. CONCLUSION: Paediatricians should remember that methaemoglobinaemia is a rare but important cause of persistently low saturations, and exchange transfusion is a reliable treatment for this condition.     

Hydrolyzed lactalbumin-based oral rehydration solution for acute diarrhoea in infants

The addition of different organic substrates to standard glucose oral rehydration solution (G-ORS) has been shown to improve the intestinal absorption of sodium and water, and thereby decrease stool losses. Therefore, we evaluated, in infants with acute diarrhoea, the safety and efficacy of three oral rehydration solutions (ORS) which had the same concentrations of electrolytes (with sodium 60 mmol/l) but different substrates of proteins and carbohydrates. One solution (LAD-ORS) contained hydrolyzed lactalbumin (LAD) with maltodextrin and sucrose, a second (MS-ORS) was identical but without LAD and a third (G-ORS) was standard glucose ORS. The three solutions were compared in a double-blind, randomized trial in 74 hospitalized well-nourished children in Panama and the United States. All three oral rehydration solutions were equally efficacious and safe in these children, 54% of whom were infected with rotavirus. There was no suggestion that hydrolyzed lactalbumin or maltodextrin provided any advantage over glucose-ORS in terms of stool output or in duration of diarrhoea. We conclude that all three solutions are efficacious in the therapy of acute diarrhoea in infants.     

Management of diarrhoea in practice

Diarrhoea, a major cause of morbidity and mortality can be produced by a variety of etiological factors. Management protocol includes assessment of the child, physical examination, lab-evaluation, assessment of severity of dehydration and rehydration therapy using either of the following-WHO-ORS, Home available fluids (HAF), sugar salt solution (SSS), improve WHO-ORS, Amino acid fortified ORS, rice based ORS, low osmolarity ORS. Intravenous fluids are required if patients can’t accept orally. Commonly observed electrolyte disturbances are hypernatremia, hyponatremia and hypokalemia. Conculsion is a common problem and can result due to electrolyte imbalance, cavernous sinus thrombosis, associated meningitis, shigella eccephalopathy and hypoglycemia in undernourished children. Treatment includes I.V. diazepam and I.V. glucose and correction of electrolyte imbalance. Additional treatment interventions include antimicrobial drugs including antibiotics, antimotility drugs, absorbents, nutritional and micro and macro nutrient supplementation.     

Treatment of acute diarrhoea in practice

The recommended treatment for acute diarrhoea includes oral rehydration and rapid refeeding is increasingly recommended. The objective of this study was to assess the home use of oral rehydration, and rehydration and realimentation in hospital. The parents of children (aged less than 4 y) with acute diarrhoea answered questions on supplementary fluids and diet during the current diarrhoea at home ( n = 129). The admitted patients ( n = 60) were weighed daily and food consumption was measured (consecutive 3-d food record). Oral rehydration had been attempted in 67% of the children managed at the outpatient department and in 65% of those admitted. The total energy intake was on average 697 kcal (95% confidence interval 639–755), which is two-thirds of that recommended for the age group. Oral rehydration has become accepted in the management of acute diarrhoea, while rapid realimentation is not yet equally endorsed.     

Oral rehydration therapy in neonates and young infants with infectious diarrhoea

The clinical response and changes in water and salt homeostasis during ORT was studied in 15 infants less than 2 months old (range 2-50 days) with acute diarrhoea. Eight patients were neonates and 7 were 1-2 months old. The oral rehydration solution contained 60 mmol sodium per litre. All patients except one were successfully rehydrated. The fluid retention was significantly higher in neonates and young infants than in infants above 3 months of age treated in the same way. One patient in the group of neonates who had a normal sodium level on admission developed hypernatremia with a sodium level of 162 mmol/l 36 hours after the start of ORT. The urinary sodium excretion was lower in the neonates than in the young infants. The results show that neonates and young infants have a lower capacity than older infants to excrete water and salt and therefore run a great risk of developing fluid and salt retention during ORT. The risk is most pronounced in neonates who, due to immaturity of the renal function, are unable to excrete excess fluid and salt.     

Serum procalcitonin and C-reactive protein in children with diarrhoea of various aetiologies

Aim: Procalcitonin (PCT) and C-reactive protein (CRP) are two acute-phase reactants with different clinical features. The study aimed to compare the diagnostic value of admission serum PCT and CRP concentrations as indicators of aetiology and intensity of inflammation in children hospitalized with diarrhoea. Methods: Serum PCT and CRP concentrations were determined on admission in 129 children hospitalized with diarrhoea. They were divided into four groups: group A: 37 children with diarrhoea as one of symptoms of ongoing systemic bacterial infection (sepsis/meningitis); group B: 36 children with bacterial enterocolitis; group C: 43 children with rotaviral enterocolitis; and group D: 13 children with active inflammatory bowel disease (IBD). For comparison serum PCT and CRP concentrations were determined in 30 healthy controls. Results: PCT concentration was >0.5 ng ml[Formula: See Text] in all 37 (100%) children with diarrhoea and systemic bacterial infection (mean 18.5 ± 3.2 ng ml[Formula: See Text]) and CRP was above 2 mg dl[Formula: See Text] in 33 (89%) of these children (11.7 ± 1.5 mg dl[Formula: See Text]). PCT concentration was ≥0.5 ng ml[Formula: See Text] in 22 of 36 (61%) children with bacterial enterocolitis (2.2 ± 0.6 ng ml[Formula: See Text]), in 3 of 43 (7%) children with rotaviral infection (0.2 ± 0 ng ml[Formula: See Text]) and in 3 of 13 (23%) patients with IBD (0.3 ± 0.1 ng ml[Formula: See Text]). CRP value was ≥2 mg dl[Formula: See Text] in 22 (61%) children from group B (5.4 ± 1.0 mg dl[Formula: See Text]), in 8 (19%) children from group C (1.3 ± 0.3 mg dl[Formula: See Text]) and in 6 (46%) patients from group D (3.3 ± 0.9 mg dl[Formula: See Text]). In the control group the PCT (0.1 ± 0.1 ng ml[Formula: See Text]) and CRP (0.03 ± 0.1 mg dl[Formula: See Text]) levels were low or undetectable.

Conclusion: In this study PCT was a more reliable marker than CRP of systemic bacterial infection in children with diarrhoea. PCT was more specific but less sensitive in the differentiation of bacterial and non-bacterial aetiology of inflammation.     

Attitude and practices regarding diarrhoea in rural community in chandigarh

The present study on diarrhoea, its prevalence, practices and awareness of mothers was conducted in 120 randomly selected households in the rural area of Chandigarh during monsoons in 1996. Inspite of access to safe drinking water and latrines in 83% and 74% of the households in the village respectively, the prevalence rate of diarrhoea in 181 under five children was observed to be 23.2%. Majority (88.1%) of children had treatment for diarrhoea whereas only half (54.8%) of children were given oral rehydration solution. 86.7% of the mothers were aware of ORS but only 18.7% could tell the correct method of its preparation. A large number of respondents implicated a variety of food items responsible for diarrhoea and restricted them during the episodes.     

Acute infectious diarrhoea in children: new insights in antisecretory treatment with racecadotril

In developing countries acute infectious diarrhoea remains one of the leading causes of death among young children, especially those under 1 year of age. In contrast, in industrialized nations the death rate is very low, although the disease is an important cause of morbidity and consumes substantial healthcare costs. A variety of viral, bacterial and parasitic organisms have been implicated in the pathogenesis of acute diarrhoea. The primary objectives of treatment of acute infectious diarrhoea are correction of dehydration with oral replacement therapy (ORT) and maintenance of good nutritional status via food intake. With regards drug therapy antimicrobial agents are not usually recommended since the disease is generally self-limiting. Racecadotril is powerful and selective enkephalinase inhibitor and has emerged as a promising drug in the antisecretory therapy of acute infectious diarrhoea in children. CONCLUSION: There is encouraging evidence that treatment with racecadotril can provide clinically relevant symptomatic relief by reducing the severity and duration of diarrhoeal episodes. The drug is well tolerated and has a favourable safety profile. However, further comparative studies and cost-effectiveness analyses are needed to define the position of the drug in the management of diarrhoeal illness in children.     

Follow-up of a child with congenital chloride diarrhoea caused by a novel mutation

Congenital chloride diarrhoea (CLD) is a rare autosomal recessive disease with chronic secretory diarrhoea and a need for lifelong salt replacement therapy. We describe a male newborn of consanguineous parents with CLD. Postnatally, frequent watery diarrhoea and electrolyte disturbances were noted from the day 8 of his life. At molecular level, a homozygous mutation was detected in the solute carrier family 26 member A3 gene (SLC26A3), confirming the clinical diagnosis of CLD. CONCLUSION: The relatively late onset of persistent clinical and laboratory signs may demonstrate a new clinical course of CLD. These findings support the need of a tight follow-up and monitoring if such a diagnosis is considered.     

Current drug therapy of protozoal diarrhoea

Protozoal infections of the gastrointestinal tract occur worldwide and have substantial morbidity and mortality. Prevalence is higher in the economically deprived regions of the world, especially the developing countries. Infections like amoebiasis and giardiasis have a worldwide distribution, being endemic in India. Apart from producing GI symptoms, growth and development of children is also impaired. It is seen that protozoa multiply rapidly in their hosts and as there is a lack of effective vaccines, chemotherapy has been the only practiced way to treat individuals and reduce transmission. The current treatment modalities for protozoal diarrhoea include 5-nitrosoimidazoles, iodoquinol, diloxanide furoate, paromomycin, chloroquine, and trimethoprim-sulphamethoxazole.     

Impact of educational intervention on knowledge of mothers regarding home management of diarrhoea

A pre and post comparison study was carried out in the field practice area of M.S. Ramaiah Medical College Bangalore, Karnataka to assess the impact of educational intervention on the knowledge of mothers of underfive children on home management of diarrhoeal diseases. Sample of 225 mothers were included in the study. The study was conducted in 3 stages. Stage I-initial knowledge, attitude and practice of mothers was assessed. Stage II-one to one educational intervention was conducted and supported by audiovisual aids and live demonstration. Stage III-included post intervention knowledge, attitude and practice after 2 months and 2 years. After the educational intervention, there was significant improvement on knowledge of mothers regarding definition of diarrhoea (P < 0.001), signs of dehydration (P < 0.001), awareness of ORS solution (P < 0.001), correct preparation of ORS solution (P < 0.001), shelf-life of ORS solution (P < 0.001), seeking health care (P < 0.001) and rational drug therapy during diarrhoea (P < 0.001). McNemar test was used to find out the change in knowledge before and after the educational intervention. The overall knowledge scores improved significantly after 2 months (P < 0.001) as well as 2 years (P < 0.001) of the educational intervention. Though the proportion of mothers retaining the knowledge at the end of 2 years dropped, yet there was significant improvement (P < 0.001) when compared to the baseline study.     

Type of milk feeding during acute diarrhoea and the risk of persistent diarrhoea: a case control study

The role of feeding breast milk, unmodified bovine milk or adapted infant formula during acute diarrhoea in protecting against or causing persistence of the episodes was investigated in a population-based case control study in an urban area of north India. After adjustment for confounding variables, exclusive breast-feeding was associated with an odds ratio of 0.06 (95% CI 0.002-2.1), a 16.5 times lower odds in favour of developing persistence of an episode. Infants fed unmodified bovine milk in addition to breast milk had an odds of 2.5 times (95% CI 1.0-9.9) in favour of developing persistence of acute diarrhoea ( p = 0.04). In infants receiving unmodified bovine milk and no breast milk, this odds ratio was 11.1 (95% CI 1.0-228.8) ( p = 0.05). This study indicates that promoting exclusive breastfeeding may reduce the persistence of diarrhoea over and above its effect in decreasing the incidence of acute diarrhoea. In urban areas of the developing countries where working mothers often use milk supplementation beyond the age of three months, our findings suggest that use of adapted spray dried formula may be safer than unmodified bovine milk with respect to the risk of developing persistent diarrhoea.     

The effect of nutritional support on weight gain of HIV-infected children with prolonged diarrhoea

AIM: To examine the effect on growth and immunity of enhanced calorie and protein provision to HIV-infected children presenting with prolonged diarrhoea. METHODS: A total of 169 HIV-infected children aged 6-36 months with diarrhoea for 7 days or more were randomly assigned to either standard nutrition support for children with prolonged diarrhoea or an enhanced diet started during hospitalisation and continued after discharge. The change in weight between enrolment and 8, 14 and 26 weeks and changes in plasma HIV-RNA and CD4 cell count at 8 and 26 weeks were estimated. RESULTS: Children receiving enhanced nutrition achieved significantly more weight gain (p < 0.001) between enrolment and 8 weeks than children on the standard diet (median increase in weight-for-age standard deviation score +1.02 vs. +0.01). After 8 weeks median weight velocity was normal and similar in both groups. The change in median CD4 count was similar in both groups. The 26-week mortality rate was high in both groups (standard support: 22%, enhanced support: 29%). CONCLUSIONS: Nutrition support of children with advanced HIV infection and prolonged diarrhoea resulted in significant and sustained weight gain, but did not improve CD4 counts or survival. These results support integrated nutrition interventions for HIV-infected children.     

Factors associated with sclerema in infants with diarrhoeal disease: a matched case-control study

Aim: To identify clinical and biochemical factors associated with sclerema in infants with diarrhoeal illness, and their outcome.
Methods: In this case-control study, we enrolled 30 infants with clinical sepsis with sclerema (cases) and another 60, age- and sex-matched infants with clinical sepsis but without sclerema (controls) from among those admitted to the special care unit (SCU) and longer stay unit (LSU) of the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) for their diarrhoeal illness from May 2005 through April 2006. Sclerema as the dependant variable while hypoxia, hypothermia, C-reactive protein (CRP) level, serum total protein and prealbumin level were the major independent variables compared in the analysis. Differences in proportions were compared by the chi-square test and differences of mean were compared by Student's t -test or Mann–Whitney test, as appropriate.
Results: The case-fatality was significantly higher among the cases than the controls (30% vs. 2%, CI 2.9–565.5). After adjusting for confounders, infants with sclerema were more likely to be hypothermic (OR 11.6, 95% CI 1.1–126.5), and have lower serum total protein (OR 1.12, 95% CI 1.04–1.21) and prealbumin (OR 1.5, 95% CI 1.1–2.3).
Conclusion: Diarrhoeal infants having clinical sepsis presenting with hypothermia, lower serum protein and prealbumin are prone to be associated with sclerema.