Admission patterns and outcomes in a paediatric intensive care unit in South Africa over a 25-year period (1971-1995).

OBJECTIVE: To describe admission and outcome patterns of diseases managed at a paediatric intensive care unit (PICU) in a developing country between 1971 and 1995, in order to provide data which will assist in improving the management of diseases and the rational allocation of health resources. METHOD: This study is based on data collated from annual audits conducted by the head of the PICU, King Edward VIII Hospital, Durban, South Africa. This unit serves a childhood population of about 3-4 million aged from 0-12 years. RESULTS: The proportion of children admitted to the ICU as a percentage of the general paediatric admission has increased from 1.5% in 1971 to 7% in 1995. During this period, 7580 children were admitted to the unit, an average of 303 cases per annum. The overall mortality rate was 35.44% (range 29.9 to 45.4%); over 90% of the children admitted were intubated and 80% required intermittent positive pressure ventilation. Common childhood vaccine preventable infections have declined substantially and have been replaced by HIV related syndromes, lower respiratory tract infections, metabolic disorders, septicaemia and hyaline membrane disease. The mean duration of ICU stay per survivor over the study period 1991-1995 was 13.891 days. Tetanus, septicaemia and HIV related diseases required the longest ICU stay per survivor (>20 days), while accidental injuries, neonatal apnoea and asthma required the shortest duration of ICU stay per survivor (<6 days); 23.9% of all deaths occurred in the first 24 h. CONCLUSION: The profile of diseases in children admitted to this PICU has changed considerably over 25 years. Some of these changes can be attributed to the shift in emphasis to primary health care, especially higher vaccination coverage rates. Profitable utilisation of limited ICU facilities would probably be enhanced by the use of outcome measures such as mortality and mean number of ICU days of stay per survivor.

Infectious diseases at the paediatric isolation units of Clairwood and King Edward VIII Hospitals, Durban. Trends in admission and mortality rates (1985-1996) and the early impact of HIV (1994-1996).

OBJECTIVE: Information on diseases of public health importance is scanty or unavailable in South Africa as a result of a weak health surveillance system. Large institutional databases of common diseases can, therefore, provide useful ancillary information for planning and policy, despite unavoidable selection bias. We conducted a 12-year retrospective review (1985-1996) of all children admitted to the only isolation facility for the Durban metropolitan region. Our aim was to document changes in admissions and mortality for common childhood infectious diseases and to detect any impact of the HIV epidemic on these diseases. RESULTS: During these years 19,037 children were admitted and annual admissions decreased by 79%. Measles accounted for the majority of admissions (58%), followed by varicella at 23%. No cases of poliomyelitis, diphtheria or cholera have been seen since 1990. Typhoid fever, mumps, tetanus and pertussis have decreased, but remain at low endemic levels. Between 1994 and 1996, 1% of measles and 15.3% of varicella cases have been associated with HIV-1 infection; this has resulted in 56% of measles deaths and 75% of varicella deaths occurring in HIV co-infected children. Overall, 60% of deaths during the past 3 years have been in HIV co-infected children. HIV testing based solely on clinical suspicion was performed in 11% and 29% of measles and varicella cases, respectively. Average all-disease mortality was 5.3%, a decrease of 87% over the study period, with measles accounting for most deaths (86%). CONCLUSIONS: The changing profile of childhood infectious diseases described at the paediatric isolation units is consistent with available national data. Probable reasons for these changes are the shift in emphasis to primary health care issues, and a gradual improvement in socio-economic conditions of the poor.

Intravenous immunoglobulin prophylaxis in neonates on artificial ventilation.

The efficacy of the prophylactic use of intravenous immunoglobulin (Ig) was evaluated in a double-blind placebo-controlled trial of 21 pairs of ventilated neonates weighing more than 1,500 g. Each infant received 0.4 g/kg/day of intravenous Ig or a similar volume of placebo daily for 5 days. Criteria used to assess the efficacy of intravenous Ig were the number of infections, the duration of ventilation therapy and time to clinical recovery. There were no significant differences in the treated and placebo groups with regard to the frequency of positive blood cultures (28.6% and 14.3%), endotracheal cultures (57.1% and 66.7%) and abnormal white cell counts (52.4% and 57.1%). On entry to the study there was no significant difference in IgG levels between the treated (974.5 mg/dl; SD 575.3) and placebo groups (818 mg/dl; SD 516.9). However, on day 6 the treated group had a mean level of 1,400.3 mg/dl (SD 426.7) versus 710.9 mg/dl (SD 377.4) in the placebo group (P < 0.05). Clinical improvement occurred within 3 days in both groups. Ventilatory support was required for 11.8 days (SD 8.3) in the treated and 11.8 days (SD 7.3) in the placebo group. Both groups required 3-4 antibiotic treatments over a period of 14-15 days. Two patients died in the treated and 4 in the placebo group, with 1 infant in each group developing bronchopulmonary dysplasia. The patients who recovered did so within 14 days. Analyses of subgroups of patients with different diagnoses revealed no differences except a trend suggesting fewer infections in term babies treated with intravenous Ig. The organisms cultured in the intravenous Ig groups were Pseudomonas, Klebsiella, Escherichia coli and Staphylococcus and in the placebo group Pseudomonas, Klebsiella and Enterobacter. The above has shown that, except for a trend in the older neonates, intravenous Ig is not of prophylactic benefit in ventilated neonates. Newer adjuncts in immunotherapy such as hyperimmune gammaglobulin or monoclonal antibodies may prove of greater value in the treatment of neonatal sepsis.

Assessment and 2-year follow-up of some factors associated with severity of respiratory infections in early childhood.

OBJECTIVE: To assess the effect of some factors on the severity of acute respiratory infection (ARI) in children. DESIGN: In a case control study, children with pneumonia were matched with controls who had upper respiratory infection. They were compared in respect of nutrition, household crowding and smoke pollution, and the presence of current viral respiratory infection. Both cohorts were followed up for 18-24 months to determine if there was a difference in subsequent respiratory sequelae. SETTING: Primary health care-based cohorts of peri-urban township children. PARTICIPANTS: Forty-eight children < 3 years of age with pneumonia (index cases) were matched by age and presentation time with controls who suffered only from upper respiratory infection. All came from underprivileged communities. Index cases were selected as they presented and the study was conducted between February 1988 and June 1991. MAIN OUTCOME MEASURE: Any difference between index cases and controls in respect of the four factors listed under 'Design'. Follow-up home visits determined whether subsequent sequelae of the two grades of ARI were different. RESULTS: The presence of current viral infection at entry to the study was evident in 21 of those with pneumonia and 12 controls (difference between groups = 19.15%, 95% confidence intervals 0.25 - 38.05, P = 0.052). Overcrowding in the home was comparable. Index homes were occupied by a mean of 3.57 (SD 1.54) children and 5.26 (SD 4.84) adults, control homes by 3.51 (SD 1.80) children and 4.36 (SD 2.02) adults. Occupancy of the room in which the child slept was also not significantly different: index group mean 4.23 (SD 1.55) and controls 4.02 (SD 1.38) (mean difference 0.21, 95% Cl 0.378 - 0.798, P = 0.485). Correlation of bedroom crowding with young age (< 1 year) or weight-for-age centiles was not significant in either cohort (r < 0.3 in all). The prevalence of viral infection was not increased by degree of crowding in either group (P = 0.636). Domestic smoke pollution was similar: cigarette smoking occurred in 75% of index homes and 69% of control homes. Wood or coal fires were used in 19% of index and 14% of control homes. The nutritional status of both groups proved to be similar. Fifteen per cent of index children and 12% of controls had weight-for-age centiles < or = 10th centile (difference = 3.26%, 95% Cl -10.72 - 17.24, P = 0.649). Two-year home follow-up visits were completed in 75% of the index and 69% of the control group. The balance were followed up for 18 months. There was no difference between index and control children in the recurrence of respiratory symptoms (P = 0.664) or need to visit a health facility (P = 0.302). CONCLUSIONS: Factors shown elsewhere to contribute to the acquisition or severity of ARI could not be demonstrated as important in this study. The children with pneumonia and their matched controls with upper respiratory infections came from equally overcrowded and smoke-filled homes, had comparable nutritional status which was not markedly poor, and had an equal incidence of current viral infection. Subsequent ill-health was not found to be greater in the pneumonia group.

Nosocomial adenovirus infection in a paediatric respiratory unit.

We report a nosocomial outbreak due to adenovirus in a paediatric respiratory unit serving a poor socio-economic community. Of 207 children admitted during an eight-month period, 24% were neonates; the median age of the remainder was 10 months. Thirty-two cases were found to be infected with adenovirus and of these 67% died. Nine were already infected with adenovirus when admitted. Twenty-three acquired the infection after admission, giving an incidence of nosocomial acquisition of 12% with a 91% mortality rate. All but one of the adenovirus infected children were being ventilated and had an endotracheal tube in place. Nosocomial spread was likely to have been from the hands of attendants, especially those manipulating suction catheters and endotracheal tube or ventilator connections. Risk factors for acquiring nosocomial infection were young age: all but two were < 1 year of age, and a relatively prolonged ward stay necessitated by the nature of the primary condition (pneumonia, bronchiolitis, laryngotracheo bronchitis, tetanus). The measures that were taken to control spread of the virus are described. Despite these, primary cases of adenovirus infection re-introduced the virus regularly over the study period. The genome analysis showed adenovirus types to be 7c2 and 7c.

Pharmacokinetic consultation program in a pediatric asthma clinic.

The effect of a clinical pharmacokinetic consultation program for theophylline on the outcomes of pediatric patients with asthma was studied. The program was established in 1989 at a pediatric asthma clinic. For each patient visit, a clinical pharmacist recorded demographic, clinical, and medication-related information and counseled the parents. When an adjustment in the theophylline dosage was indicated, the pharmacist calculated the appropriate dosage using population pharmacokinetic values. If the pediatrician requested a measurement of the serum theophylline concentration, the time when the blood sample was drawn relative to the last dose was recorded, an average serum theophylline concentration at steady state and individualized pharmacokinetic values were calculated, and the dosage was adjusted accordingly. Patient data were compared among three stages: (1) the month before and the month of entry into the program, (2) months 5 and 6 after entry, and (3) months 11 and 12 after entry. A total of 44 patients were studied during each of stages 1 and 2, and 29 patients were reviewed during stage 3. There was a significant improvement in wheezing from stage 1 to stage 2 and in exercise tolerance and nocturnal coughing from stage 1 to stage 2 and stage 1 to stage 3. Forced expiratory volume in one second improved significantly from stage 1 to stage 2, and there was a significant reduction in the necessity for hospital visits for the treatment of exacerbations of asthma between stages 1 and 2. The daily weight-adjusted dose of theophylline increased significantly after the program began. Asthmatic children taking theophylline had improvements in outcome variables after pharmacokinetic consultation and medication counseling were initiated.

Ipratropium bromide delivered by metered-dose aerosol to infant wheezers.

Two methods of administration of ipratropium bromide (Atrovent; Boehringer Ingelheim) to wheezing children less than 25 months of age were compared: (i) the conventional nebulisation (15 children); and (ii) a metered-dose aerosol plus spacer and mask (MDA group, 17 children). The drug induced a significant and similar fall in respiratory rate in both groups. Transcutaneous carbon dioxide pressure was also reduced significantly but was more marked in the MDA group. This increase in alveolar ventilation was similar in those less than 12 months as in older children; in those with recurrent or with first time wheezing; and in those with radiological evidence of pneumonia. Clinical assessment of bronchospasm and recession was recorded as improved in over 80% of both groups. The MDA delivery of ipratropium bromide was as effective as nebulisation and was more convenient, since it required less time and equipment. It was also well accepted by the small patients.

Prolonged after-effects of pneumonia in children.

Sixty-two black children were prospectively followed up for 1-7 years after pneumonia contracted at a median age of 17 months. In 55% of cases the pneumonia was measles-associated and 27% had serological evidence of infection with other respiratory viruses. Recurrence of cough or wheeze for more than 6 months occurred in 85% with just over 50% having recovered during the follow-up period. While the highest incidence of persistent symptoms occurred in children after measles superinfected with another virus, this was not significant. Abnormal radiographic features persisted in 53% of children and consisted of peribronchial and/or parenchymal lesions. Abnormal large and small airway calibre and/or bronchial hyperreactivity were found in one-third of children, and were significantly more common in those children whose main symptom was recurrent wheezing. Clinical and lung function abnormalities years after lower respiratory tract infection in this group of disadvantaged children compare with reports from more privileged groups. Recognition that long-term sequelae occur may prevent inappropriate subsequent management of symptomatic children.

Normal values for simple lung function tests in South African Asian children.

Normal lung function values have frequently been shown to be racially specific. This study of 1072 boys and girls establishes normal standards for peak expiratory flow rate, forced expiratory volume in 1 s, and forced vital capacity in Asian (Indian) children aged 5-14 years. These values are compared with those of American white and black children and of Indian and British Asians.

Tetanus in children: an 11-year review.

One hundred and three cases of tetanus in children 1-12 years of age were reviewed. Sixty-six per cent had severe disease, half of whom required management with total muscle paralysis and intermittent positive pressure ventilation (IPPV), and 70% in this group developed signs of sympathetic overactivity (SOA). Control of SOA with morphia 0.5-1 mg/kg/dose given 1-4 times a day appears to have decreased the mortality rate from this complication of severe tetanus. There was a relative resistance to drug control of SOA in the youngest children. High output renal failure developed in two children, an incidence much the same as reported in severely affected adults. The overall mortality rate of this series was 14.5%: all the deaths were amongst those severely affected. The cause of death could be attributed to tetanus in half, while in the remainder it resulted from complications of intensive therapy. Tetanus in children resembles the disease in adults.

Morphine in tetanus--the management of sympathetic nervous system overactivity.

Morphine was administered intravenously in bolus doses 6-hourly to 10 patients; 9 developed signs of sympathetic overactivity and required increased morphine dosage. The mean daily morphine dosage was 103 +/- 36 mg and the maximum daily dosage was 170 +/- 65 mg. In all cases morphine decreased the mean arterial blood pressure (mean 18%; P less than 0.01) and heart rate (mean 7%; P less than 0.01). In 7 cases the cardiac output fell minimally (mean 7%; P = 0.07), while the systemic vascular resistance decreased (mean 12%; P less than 0.01) in 8 cases. Nine patients survived, 1 died from renal failure and septicaemia. There were no apparent problems with either opiate withdrawal or addiction. No patient required either alpha- or beta-adrenergic blockers and the consequent simplified management constitutes a significant improvement in control of these patients.

Nasotracheal intubation versus tracheostomy for intermittent positive pressure ventilation in neonatal tetanus.

Fifty-two neonates with tetanus who required muscle paralysis and IPPV were managed alternatively with naso-tracheal intubation or tracheostomy. The complications of the two techniques were compared. Planned extubation caused less problems in the intubated than in the tracheostomized children, and secondary infection occurred less often. Accidental extubation, however, was a significant hazard in the intubated child.

A retrospective study of children after pneumonia.

Sixteen Black children were examined 5 years after hospitalization for pneumonia. Sixty-three per cent had had recurrent symptoms since that time. Of this group 60% had physical signs present although they were reportedly symptom-free at the time of examination. A family history of asthma was common in the symptom-free group and in the group with intermittent symptoms, but in only 1 child could a minor degree of exercise-induced bronchospasm be produced. Airway obstruction was detected in 19% of the children using peak expiratory flow rate measurements. Only 1 child had a completely normal chest radiograph at the follow-up examination. In this retrospective study long-term sequelae of pneumonia in early childhood were common and should be considered in the assessment of children with recurrent symptoms and signs and/or persistent radiographic changes.

Immunity to and infant mortality from measles.

The age-related sequential immune response to natural measles was investigated in order to establish the role of immunodeficiency in the high infant mortality from infectious diseases. There was no difference in lymphocyte transformation, complement-fixing antibody titres, serum IgG, IgM, IgA, C3 and factor B levels, total haemolytic complement and the alternative pathway of complement over a 6-week period after onset of the rash in those younger than 12 months (group A) compared with children older than 12 months (group B). The absolute number of peripheral blood lymphocytes, comprising T, B and null cells, was higher on different days in group A compared with group B. Throughout the 6 weeks group A had higher haemagglutination inhibition antibody levels and lower serum C4 levels than Group B. The inhibition of leucocyte migration to measles antigen was similar in the two groups, except on day 28 when it was significantly higher in group B. There were 5 deaths, all in infants younger than 15 months of age. Most immunological reactions studied were not age-dependent, while those differences detected in the younger age group involved factors known to indicate a good prognosis. Therefore, the high mortality rate reported for measles in infants is unlikely to be due to immunodeficiency in this age group.

Renal function in tetanus.

In twenty-eight patients suffering from tetanus, renal function was evaluated from admission for a period of 2 weeks. Investigations included daily blood urea, osmolality and creatinine and urinary osmolality and sodium. Free water clearance (CH2O) was calculated. The patients were divided into those requiring tracheostomy and sedation alone (Group I) and those with more severe tetanus requiring total muscle paralysis and IPPV (Group II). The latter group also had evidence of sympathetic nervous overactivity (SOA). Daily blood urea, serum creatinine and osmolality showed no significant difference between the two groups except during the phase of uremia. Mean urinary sodium was significantly different between the two groups (p less than 0.001). Four patients in Group II developed an abnormal plasma urea (Group IIb). In one patient the rise in urea followed resuscitation from cardiac arrest and the remaining three patients had in common severe cardiovascular instability associated with SOA. All four patients were non-oliguric during the phase of uremia. Only one patient with renal failure survived, compared with a 75% survival in the patients with SOA without renal failure and a 100% survival in Group I. Tetanus complicated by renal failure has a poor prognosis.

Viral infections in clinical pertussis.

Of 44 children with clinical pertussis 29 (66%) had serological evidence of concurrent infection with respiratory viruses or Mycoplasma pneumoniae. The commonest superinfection was by mycoplasma (32%), followed by respiratory syncytial virus (27%) and adenoviruses (16%). The high prevalence of viral infections, many being multiple, supports the theory that pertussis predisposes to such infections or vice versa.

Labetalol in tetanus. The treatment of sympathetic nervous system overactivity.

The cardiovascular instability in some cases of severe tetanus is due to increased circulating catecholamines. In 15 patients with this complication of tetanus, labetalol, a drug with alpha- and beta-peripheral adrenergic blocking properties, was used in management. The drug was administered orally, by i.v. bolus or by continuous infusion. Wide variation in dosage was needed both from case to case and in the same patient during the course of his disease. In most cases the pulse and blood pressure were reduced by labetalol, although their variability was not much improved. The effect on the cardiac output and systemic vascular resistance ranged from modest reduction in both, to marked effect on cardiac output without any change in systemic vascular resistance. The alpha-adrenergic blockage of labetalol is known to be less powerful than the beta-blocking effect, and this property could be a disadvantage in the management of sympathetic overactivity in tetanus.

Further predictive indices of clinical severity of measles.

Predictive indices for the outcome of measles were sought from a clinical and immunological study. A poor outcome was defined as death or persistence of bronchopulmonary disease 6 weeks after onset. The 47 Black children studied were well nourished and lymphopenic (absolute lymphocyte count less than 2 000/mm3) in the first 2 days of the exanthem. The latter feature has previously been shown to carry a poor prognosis. Eight of the children recovered fully, 5 died and 34 had residual lung changes at 6 weeks. Other factors which could be related to prognosis in this group of children already at risk of severe disease were more extensive pneumonia and normal or minimally reduced serum complement C3 levels early in the course of the disease. A less than twofold rise in haemagglutinin-inhibiting antibody titre was also associated with a poor prognosis.

Levamisole therapy in children at risk from severe measles.

A placebo-controlled trial of Levamisole in 47 black children with measles is reported. The children were of satisfactory nutrition but at risk from severe disease as judged by a lymphopenia of less than 2000 X 10(-9)/m3 (less than 2000/mm3) early in the exanthem. A placebo or Levamisole (2.5 mg/kg/dose) were given orally weekly for six weeks. Death or persistence of radiological pneumonia at six weeks occurred in 74% of the Levamisole and 92% of the placebo group. No side effects of the drug were noted. The immune responses that were monitored for six weeks were total lymphocyte and lymphocyte subpopulation counts, PHA stimulated lymphocyte transformation, leucocyte migration inhibition, measles antibody titres and serum levels of immunoglobulins and complement components. In none of these was a significant difference found between the two groups. While there was a trend clinically towards complete recovery in the group that received Levamisole, statistically it was not significant, and therefore Levamisole cannot be recommended for treatment of measles.