389
Hypernatraemia surveillance during a national diarrhoeal diseases control project in Egypt
The nationwide introduction of oral rehydration therapy to Egypt has led to improvement in diarrhoea case management and a fall in infant and child mortality. With the wider use of oral rehydration solution (ORS) prepared from packets, the incidence of hypernatraemia (serum sodium > 150 mmol/l) in inpatients with dehydration seen at Abu El-Reeche Hospital, Cairo, increased between 1980 and 1984. Systematic surveillance of hypernatraemia in the outpatient rehydration unit began in late 1984, and we report trends in hypernatraemia and analyses of key variables affecting its incidence in dehydrated children. In 1980, 17 of 100 children sampled had hypernatraemia and 2 had severe hypernatraemia (ie, serum sodium >165 mmol/l). The frequency in inpatients peaked at 49% of 222 children in 1984 (19% with severe hypernatraemia). Between 1986 and 1989, at least 1000 dehydrated outpatients were surveyed each year; by 1989 the incidence of hypernatraemia had fallen to around 10% (2% severe hypernatraemia). The rise and decline coincided with increasing use of ORS and then increasing ability of mix the solution mothers to correctly. Hypernatraemia was positively related to the quantity of ORS taken, severity of dehydration, nutritional status, and the cooler season, and negatively related to age and duration of diarrhoea. Explanations for our findings include improved use of ORS and better case-management. Good practice promoted through the mass media has facilitated these changes; if the standard of ORS use is not maintained, there may be a case for reducing the sodium content of ORS.
Introduction Diarrhoea remains a potentially life-threatening illness for young children in developing countries, dehydration being responsible for most deaths. Survivors of multiple episodes of diarrhoea are likely to become malnourished. Oral rehydration therapy (ORT) is effective in reducing mortality1 and protecting nutrition2 when used correctly. The packeted World Health Organisation (WHO) ORT formulation was introduced into Egyptian public clinics and commercial pharmacies in 1978. The National Control of Diarrheal Diseases Project (NCDDP) began in late 1982, under a grant from the US Agency for International
Development,
and lasted until
October,
1991.
The
NCDDP has stimulated production and wide distribution of oral rehydration salts (ORS) and special measuring cups; trained thousands of health workers in the use of ORS; sponsored research and evaluation; and through the mass
of ORS, proper feeding At present, about two-thirds of mothers of small children in Egypt have used ORS, and mortality from diarrhoea in infants and children has fallen from 49/1000 and 9-7/1000, respectively, in 1977 to 12-3/1000 and 2-3/1000 in 1987.1 The effectiveness and simplicity of ORS means that many children with diarrhoea are rehydrated at home (often after consultation with a doctor). However, if ORS is used incorrectly, some children may be harmed. Use of too much volume may interfere with nutrition, whereas too little volume delays effective rehydration, and overconcentration of the solution may lead to hypernatraemia.3 Between 1980 and 1984, the incidence of hypematraemia in children treated for diarrhoea as inpatients at Abu El-Reeche Hospital, Cairo, appeared to increase. Therefore, beginning in 1984, continuing surveillance of hypematraemia was started at the hospital. Abu El-Reeche Hospital treats about 20 000 cases per year of diarrhoea. We report the trends revealed by surveillance, and an analysis of risk factors for
media, promoted
correct use
practices, and hygiene.
’
hypematraemia. Methods Surveillance, 1985-89 Surveillance of serum sodium in children with diarrhoea in November, 1984. Over 95% of the children were treated as outpatients, most with ORS, but some by nasogastric tube and a few with intravenous fluids followed by ORS. The WHO formulation of ORS was used. Because sodium concentrations were seldom known before the end of the treatment, most children with hypematraemia were also treated with ORS as outpatients. Cases were selected for measurement of serum sodium by one paediatrician throughout the study. Patients fulfilled the following criteria: diarrhoea, either acute or prolonged, with clinical signs of dehydration but not shock or coma (in 1986, children with more obvious signs of dehydration were over-sampled); and no complicating illness such as pneumonia, suspected sepsis, or central nervous system infection. The selected patients gave a sample of venous blood. Between November, 1984, and October, 1989, 5207 children were sampled-229 in the first year as the system was developed, and between 1037 and 1482 children per year in the four subsequent years. On average, the November-to-February period contributed 19% of each year’s sample, and the subsequent four-month periods 40 and 41 %. These differences are related to the incidence of diarrhoea throughout the year. A detailed questionnaire recorded each child’s age, sex, clinical history, signs of dehydration, the Fortin-Parent dehydration score,4,s post-rehydration body weight (compared with National Centre for Health Statistics standards), and food and fluid intake in
began
ADDRESSES: Cairo University Faculty of Medicine, Cairo, Egypt (Prof I. M. Fayad, MD, M. Kamel, MD,); John Snow Inc, Boston, Massachusetts, USA, and the National Control of Diarrheal Diseases Project, Ministry of Health, Cairo (N. Hirschhorn, MD); and Gastroenteritis Research Unit, Abu ElReeche Hospital, Cairo University, Cairo (M Abu-Zikry, MSc). Correspondence to Prof Ibrahim M. Fayad, Gastroenteritis Unit, Cairo University Children’s Hospital (Abu EI-Reeche Hospital), Mounira,
Cairo, Egypt.
390
TABLE III-RELATION OF HYPERNATRAEMIA TO PATIENT
TABLE I-PATIENT CHARACTERISTICS
VARIABLES
*Year runs from November until October tFortin-Parent score approximates one pomt for every 1 % loss of
body weight5
the past 24 h (including amount of ORS). Mothers were asked how much water they used to dissolve the ORS, and whether they used the special 200 ml NCDDP cup filled to the scored line or the small soft-drink bottle filled to the neck (both methods are shown regularly in television commercials and in face-to-face education). The following children, all aged less than two years, were also sampled in 1987: 104 normal children and 80 malnourished children without diarrhoea, and 528 children with diarrhoea but no
dehydration. Serum sodium was measured with ’Nova-1’ (Nova Biomedical, Waltham, Massachusetts, USA), or ’CC 614’, or ’CC 288’ (both Ciba-Coming, Medfield, Massachusetts, USA) Na/K ion-selective electrodes. Quality-control testing was done with standards supplied by the manufacturers of the electrodes and with lyophilised sera supplied by Boehringer (Mannheim, Germany) and Bioanalytics (Palm City, Florida, USA). Quality-control tests were done before each run and during long runs. Samples that proved to be hypematraemic were assayed on a second machine, and some were subjected to osmolality measurement with a ’Microosmette’ osmometer (Precision Systems, Natick, Massachusetts, USA). Children were classified as hypematraemic if they had a serum sodium greater than 150 mmol/1. Associations with possible explanatory variables were examined by chi-square significance testing. Multiple regression analyses were done on those variables significantly associated with hypematraemia. Values of independent variables were entered in a single step into the equation in which the concentration of serum sodium was the dependent variable. Partial correlation coefficients were calculated to show the relative importance of each factor contributing to the variability of serum sodium. Relative risks for presence of hypematraemia were assessed for the variable with the largest partial correlate with serum sodium concentration-ie, quantity of ORS taken in the past 24 h. Relative risk of hypematraemia by ORS intake may be confounded by several variables. We estimated the importance of potential confounders by calculating relative risks for hypematraemia by levels of ORS intake in children with and without the potential confounder, and then taking a weighted average. If the weighted average was not appreciably less than the summary relative risk, confounding could reasonably be excluded; the exception to this rule-severity of dehydration-is discussed in the results section. TABLE II-PATIENT SERUM SODIUM CONCENTRATION BY YEAR
NS not
significant.
Presurveillance sampling, 1980-84 The oral rehydration ward was established at Abu El-Reeche Hospital in 1980. From then until October, 1984, children admitted with moderate to severe dehydration had their serum sodium measured by flame photometry if they were part of a clinical study. Case selection therefore favoured finding a higher incidence of hypematraemia compared with the outpatient surveillance samples of later years. On the other hand, flame photometry somewhat underestimates concentrations of sodium compared with ionselective electrodes: 1240 serum samples taken in 1986 were measured by both methods; the mean (95% CI) value by flame photometry was 143-3 (142’7-143’9) mmol/1 and by ion-selective electrode 146-3 (145-7-146-9) mmol/1. With these opposing biases, we present the data as an approximation of the trend in hypematraemia incidence beginning in 1980.
National data
on
ORS
use
Studies done by the NCDDP in 1984-87 determined the proportion of mothers with children under two years old who had used ORS, and, of this group, the proportion who could demonstrate correct mixing of the solution. In each year, 1500 mothers were selected at random from rural and urban populations. Regional studies of ORS use are available from before 1984. The details of these studies will be published elsewhere.
Results The characteristics of patients sampled from 1986 to 1989 shown in table I. Over 80% were infants (less than one-year old), about 70% were undernourished, and many had prolonged diarrhoea. Apart from 1986, when severely dehydrated children were over-sampled, the degree of dehydration remained constant, but the incidence of prolonged diarrhoea tended to increase. In 1986, 1987, 1988, and 1989,93%, 96%, 97%, and 98%, respectively, of are
391
TABLE IV-PARTIAL CORRELATION COEFFICIENTS OF INDEPENDENT VARIABLES WITH VARIATION IN SERUM SODIUM*
I
i
I
TABLE VI-SERUM SODIUM CONCENTRATIONS (mmol/I) AND RISKS FOR HYPERNATRAEMIA BY LEVELS OF ORS INTAKE IN PAST 24 H
I
*All coefficients statistically significant (F-test) at p< ’02, except season (p= 022), age in 1987 (p= 04), and season 1989 (not significant).
in
1987,
mothers knew the volume of water required to prepare ORS. Table II shows the results of serum sodium measurements and table in shows the relation of several variables to hypematraemia. Hypernatraemia was significantly more likely in younger infants, in patients with severe dehydration, and in the cooler part of the year, and was significantly associated with amount of ORS intake in the previous 24 h. Hypernatraemia was less likely with undernutrition, more prolonged diarrhoea, and in the hot season. In 1986, we also found a significant positive relation between concentration of serum sodium (as a continuous variable) and intake of milk formula (p 0003) or fruit juice (p 0-02), and increasing educational level of either parent (p
Hypernatraemia surveillance during a national diarrhoeal diseases control project in Egypt
The nationwide introduction of oral rehydration therapy to Egypt has led to improvement in diarrhoea case management and a fall in infant and child mortality. With the wider use of oral rehydration solution (ORS) prepared from packets, the incidence of hypernatraemia (serum sodium > 150 mmol/l) in inpatients with dehydration seen at Abu El-Reeche Hospital, Cairo, increased between 1980 and 1984. Systematic surveillance of hypernatraemia in the outpatient rehydration unit began in late 1984, and we report trends in hypernatraemia and analyses of key variables affecting its incidence in dehydrated children. In 1980, 17 of 100 children sampled had hypernatraemia and 2 had severe hypernatraemia (ie, serum sodium >165 mmol/l). The frequency in inpatients peaked at 49% of 222 children in 1984 (19% with severe hypernatraemia). Between 1986 and 1989, at least 1000 dehydrated outpatients were surveyed each year; by 1989 the incidence of hypernatraemia had fallen to around 10% (2% severe hypernatraemia). The rise and decline coincided with increasing use of ORS and then increasing ability of mix the solution mothers to correctly. Hypernatraemia was positively related to the quantity of ORS taken, severity of dehydration, nutritional status, and the cooler season, and negatively related to age and duration of diarrhoea. Explanations for our findings include improved use of ORS and better case-management. Good practice promoted through the mass media has facilitated these changes; if the standard of ORS use is not maintained, there may be a case for reducing the sodium content of ORS.
Introduction Diarrhoea remains a potentially life-threatening illness for young children in developing countries, dehydration being responsible for most deaths. Survivors of multiple episodes of diarrhoea are likely to become malnourished. Oral rehydration therapy (ORT) is effective in reducing mortality1 and protecting nutrition2 when used correctly. The packeted World Health Organisation (WHO) ORT formulation was introduced into Egyptian public clinics and commercial pharmacies in 1978. The National Control of Diarrheal Diseases Project (NCDDP) began in late 1982, under a grant from the US Agency for International
Development,
and lasted until
October,
1991.
The
NCDDP has stimulated production and wide distribution of oral rehydration salts (ORS) and special measuring cups; trained thousands of health workers in the use of ORS; sponsored research and evaluation; and through the mass
of ORS, proper feeding At present, about two-thirds of mothers of small children in Egypt have used ORS, and mortality from diarrhoea in infants and children has fallen from 49/1000 and 9-7/1000, respectively, in 1977 to 12-3/1000 and 2-3/1000 in 1987.1 The effectiveness and simplicity of ORS means that many children with diarrhoea are rehydrated at home (often after consultation with a doctor). However, if ORS is used incorrectly, some children may be harmed. Use of too much volume may interfere with nutrition, whereas too little volume delays effective rehydration, and overconcentration of the solution may lead to hypernatraemia.3 Between 1980 and 1984, the incidence of hypematraemia in children treated for diarrhoea as inpatients at Abu El-Reeche Hospital, Cairo, appeared to increase. Therefore, beginning in 1984, continuing surveillance of hypematraemia was started at the hospital. Abu El-Reeche Hospital treats about 20 000 cases per year of diarrhoea. We report the trends revealed by surveillance, and an analysis of risk factors for
media, promoted
correct use
practices, and hygiene.
’
hypematraemia. Methods Surveillance, 1985-89 Surveillance of serum sodium in children with diarrhoea in November, 1984. Over 95% of the children were treated as outpatients, most with ORS, but some by nasogastric tube and a few with intravenous fluids followed by ORS. The WHO formulation of ORS was used. Because sodium concentrations were seldom known before the end of the treatment, most children with hypematraemia were also treated with ORS as outpatients. Cases were selected for measurement of serum sodium by one paediatrician throughout the study. Patients fulfilled the following criteria: diarrhoea, either acute or prolonged, with clinical signs of dehydration but not shock or coma (in 1986, children with more obvious signs of dehydration were over-sampled); and no complicating illness such as pneumonia, suspected sepsis, or central nervous system infection. The selected patients gave a sample of venous blood. Between November, 1984, and October, 1989, 5207 children were sampled-229 in the first year as the system was developed, and between 1037 and 1482 children per year in the four subsequent years. On average, the November-to-February period contributed 19% of each year’s sample, and the subsequent four-month periods 40 and 41 %. These differences are related to the incidence of diarrhoea throughout the year. A detailed questionnaire recorded each child’s age, sex, clinical history, signs of dehydration, the Fortin-Parent dehydration score,4,s post-rehydration body weight (compared with National Centre for Health Statistics standards), and food and fluid intake in
began
ADDRESSES: Cairo University Faculty of Medicine, Cairo, Egypt (Prof I. M. Fayad, MD, M. Kamel, MD,); John Snow Inc, Boston, Massachusetts, USA, and the National Control of Diarrheal Diseases Project, Ministry of Health, Cairo (N. Hirschhorn, MD); and Gastroenteritis Research Unit, Abu ElReeche Hospital, Cairo University, Cairo (M Abu-Zikry, MSc). Correspondence to Prof Ibrahim M. Fayad, Gastroenteritis Unit, Cairo University Children’s Hospital (Abu EI-Reeche Hospital), Mounira,
Cairo, Egypt.
390
TABLE III-RELATION OF HYPERNATRAEMIA TO PATIENT
TABLE I-PATIENT CHARACTERISTICS
VARIABLES
*Year runs from November until October tFortin-Parent score approximates one pomt for every 1 % loss of
body weight5
the past 24 h (including amount of ORS). Mothers were asked how much water they used to dissolve the ORS, and whether they used the special 200 ml NCDDP cup filled to the scored line or the small soft-drink bottle filled to the neck (both methods are shown regularly in television commercials and in face-to-face education). The following children, all aged less than two years, were also sampled in 1987: 104 normal children and 80 malnourished children without diarrhoea, and 528 children with diarrhoea but no
dehydration. Serum sodium was measured with ’Nova-1’ (Nova Biomedical, Waltham, Massachusetts, USA), or ’CC 614’, or ’CC 288’ (both Ciba-Coming, Medfield, Massachusetts, USA) Na/K ion-selective electrodes. Quality-control testing was done with standards supplied by the manufacturers of the electrodes and with lyophilised sera supplied by Boehringer (Mannheim, Germany) and Bioanalytics (Palm City, Florida, USA). Quality-control tests were done before each run and during long runs. Samples that proved to be hypematraemic were assayed on a second machine, and some were subjected to osmolality measurement with a ’Microosmette’ osmometer (Precision Systems, Natick, Massachusetts, USA). Children were classified as hypematraemic if they had a serum sodium greater than 150 mmol/1. Associations with possible explanatory variables were examined by chi-square significance testing. Multiple regression analyses were done on those variables significantly associated with hypematraemia. Values of independent variables were entered in a single step into the equation in which the concentration of serum sodium was the dependent variable. Partial correlation coefficients were calculated to show the relative importance of each factor contributing to the variability of serum sodium. Relative risks for presence of hypematraemia were assessed for the variable with the largest partial correlate with serum sodium concentration-ie, quantity of ORS taken in the past 24 h. Relative risk of hypematraemia by ORS intake may be confounded by several variables. We estimated the importance of potential confounders by calculating relative risks for hypematraemia by levels of ORS intake in children with and without the potential confounder, and then taking a weighted average. If the weighted average was not appreciably less than the summary relative risk, confounding could reasonably be excluded; the exception to this rule-severity of dehydration-is discussed in the results section. TABLE II-PATIENT SERUM SODIUM CONCENTRATION BY YEAR
NS not
significant.
Presurveillance sampling, 1980-84 The oral rehydration ward was established at Abu El-Reeche Hospital in 1980. From then until October, 1984, children admitted with moderate to severe dehydration had their serum sodium measured by flame photometry if they were part of a clinical study. Case selection therefore favoured finding a higher incidence of hypematraemia compared with the outpatient surveillance samples of later years. On the other hand, flame photometry somewhat underestimates concentrations of sodium compared with ionselective electrodes: 1240 serum samples taken in 1986 were measured by both methods; the mean (95% CI) value by flame photometry was 143-3 (142’7-143’9) mmol/1 and by ion-selective electrode 146-3 (145-7-146-9) mmol/1. With these opposing biases, we present the data as an approximation of the trend in hypematraemia incidence beginning in 1980.
National data
on
ORS
use
Studies done by the NCDDP in 1984-87 determined the proportion of mothers with children under two years old who had used ORS, and, of this group, the proportion who could demonstrate correct mixing of the solution. In each year, 1500 mothers were selected at random from rural and urban populations. Regional studies of ORS use are available from before 1984. The details of these studies will be published elsewhere.
Results The characteristics of patients sampled from 1986 to 1989 shown in table I. Over 80% were infants (less than one-year old), about 70% were undernourished, and many had prolonged diarrhoea. Apart from 1986, when severely dehydrated children were over-sampled, the degree of dehydration remained constant, but the incidence of prolonged diarrhoea tended to increase. In 1986, 1987, 1988, and 1989,93%, 96%, 97%, and 98%, respectively, of are
391
TABLE IV-PARTIAL CORRELATION COEFFICIENTS OF INDEPENDENT VARIABLES WITH VARIATION IN SERUM SODIUM*
I
i
I
TABLE VI-SERUM SODIUM CONCENTRATIONS (mmol/I) AND RISKS FOR HYPERNATRAEMIA BY LEVELS OF ORS INTAKE IN PAST 24 H
I
*All coefficients statistically significant (F-test) at p< ’02, except season (p= 022), age in 1987 (p= 04), and season 1989 (not significant).
in
1987,
mothers knew the volume of water required to prepare ORS. Table II shows the results of serum sodium measurements and table in shows the relation of several variables to hypematraemia. Hypernatraemia was significantly more likely in younger infants, in patients with severe dehydration, and in the cooler part of the year, and was significantly associated with amount of ORS intake in the previous 24 h. Hypernatraemia was less likely with undernutrition, more prolonged diarrhoea, and in the hot season. In 1986, we also found a significant positive relation between concentration of serum sodium (as a continuous variable) and intake of milk formula (p 0003) or fruit juice (p 0-02), and increasing educational level of either parent (p
