Characteristics and outcome of cardiopulmonary resuscitation in hospitalised African children.

OBJECTIVE: To review the characteristics and outcome of cardiopulmonary resuscitation in children at a rural hospital in Kenya. PATIENTS AND METHOD: All children aged 0-14 years who experienced > or =1 episode of respiratory or cardiopulmonary arrest during April 2002--2004 were prospectively identified. Demographic variables, cause of hospitalisation, type and duration of arrest, resuscitation measures taken and outcomes were determined. RESULTS: 114 children experienced at least one episode of respiratory arrest (RA) or cardiopulmonary arrest (CPA). Cardiopulmonary resuscitation (CPR) was performed on all children. "Do not resuscitate order" (DNR) was given in 15 patients after initial resuscitation. Eighty two patients (72%) had RA and 32 (28%) had CPA. 25/82 (30%) patients with RA survived initial CPR compared to 5/32 (16%) with CPA. Survival at discharge was 22% (18/82) in children who had RA while no one with CPA survived at discharge. The leading underlying diseases were severe malaria, septicaemia and severe malnutrition. Prolonged resuscitation beyond 15 min and receiving adrenaline [epinephrine] (at least one dose of 10 microg/kg IV) were predictive of poor final outcome. CONCLUSION: Cardiopulmonary arrest after admission has a very poor prognosis in our hospital. Infectious diseases are the main underlying causes of arrest. If a child fails to respond to the basic tenements of PALS within 15 min then it is unlikely that further efforts to sustain life will be fruitful in hospitals where ventilation facilities are not present.

Haemolytic uraemic syndrome in children admitted to a rural district hospital in Kenya.

We studied children admitted to Kilifi District Hospital, Kenya, between 1997 and 2005 with haemolytic uraemic syndrome (HUS) and reviewed their records in order to determine the clinical features and outcomes of the disease. Thirty-one children fulfilled the criteria: 21 (68%) had diarrhoea-associated HUS (D + HUS), the remainder did not (D-HUS); five had involvement of the central nervous system. Those with D-HUS had lower haemoglobin and platelet counts when compared with those with D + HUS. The overall mortality rate was 55% (17/31) with no significant difference between the two groups. Severe hyponatraemia ([Na(+)] <120 mmol/L) predicted a poor outcome. Shigella dysenteriae was the most common isolated organism in the stool and Escherichia coli and S. dysenteriae were the most common blood isolates. HUS carries a high mortality rate and D-HUS is as common as D + HUS.

The role of sequential administration of sulphadoxine/pyrimethamine following quinine in the treatment of severe falciparum malaria in children.

Sulphadoxine/pyrimethamine (SP) is often administered with quinine in the treatment of severe falciparum malaria to shorten the course of quinine. The efficacy of SP alone in the treatment of non-severe malaria has been declining rapidly in East Africa, raising concerns of the usefulness of a shortened course of quinine followed SP. We audited the efficacy of quinine/SP in the treatment of severe malaria in Kenyan children. Children with severe falciparum malaria were treated with parenteral quinine followed by a single oral dose of SP. A clinical evaluation was performed 3 weeks later in which a blood sample was obtained for full haemogram, blood slide and analysis of the parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) codons, mutations of which are associated with resistance to SP. A total of 452 children were enrolled, of whom 374 completed the study. Fifty-two (13.9%) children were parasitaemic by 3 weeks of whom 17 (4.5%) had fever as well. The treatment failure group had a significantly higher parasitaemia (129 061 vs. 43 339; P<0.001) and haemoglobin on admission, but only admission parasitaemia independently predicted treatment failure. Those with treatment failure had a significantly lower rise in haemoglobin at 3 weeks compared with treatment successes (9.0 vs. 10.0 g/dl). Of the 76 parasite isolates collected before treatment, 40 (53%) were triple mutant DHFR-double DHPS (Tp-Db), the genotype most associated with SP resistance. Three weeks after SP treatment, the proportion of Tp-Db increased to 72% (31/43). The high treatment failure rate and proportion of parasites with Tp-Db negate the use of SP to shorten the course of quinine treatment in East Africa.

Severe P. falciparum malaria in Kenyan children: evidence for hypovolaemia.

BACKGROUND: The role of volume resuscitation in severe Plasmodium falciparum malaria is controversial. AIM: To examine the role of hypovolaemia in severe childhood malaria. STUDY DESIGN: Retrospective review. METHODS: We studied 515 children admitted with severe malaria to a high-dependency unit (HDU) in Kilifi, Kenya. On admission to the HDU, children underwent a further assessment of vital signs and a standard clinical examination. RESULTS: Factors associated with a fatal outcome included deep breathing or acidosis (base excess below -8), hypotension (systolic blood pressure <80 mmHg), raised plasma creatinine (>80 micro mol/l), low oxygen saturation (<90%), dehydration and hypoglycaemia (<2.5 mmol/l). Shock was present in 212/372 (57%) children, of whom 37 (17.5%) died, and was absent in 160, of who only 7 (4.4%) died (chi(2) = 14.9; p = 0.001). DISCUSSION: Impaired tissue perfusion may play a role in the mortality of severe malaria. Moreover, volume resuscitation, an important life-saving intervention in children with hypovolaemia, should be considered in severe malaria with evidence of impaired tissue perfusion.

The role of reduced red cell deformability in the pathogenesis of severe falciparum malaria and its restoration by blood transfusion.

As reduced red cell deformability (RCD) can contribute to derangement of the microcirculation, a central feature in the pathogenesis of severe malaria, RCD was measured with a laser diffraction technique in 232 consecutive patients with falciparum malaria on the Kenyan coast, of whom 99 had severe disease. RCD on admission (measured as elongation index [EI] at shear stress = 1.7 Pa) was reduced in proportion with severity of disease (fatal outcome: EI = 0.182 (SD = 0.048), survivors from severe disease: EI = 0.217 (SD = 0.043), uncomplicated malaria: EI = 0.249 (SD = 0.030), healthy controls: EI = 0.268 (SD = 0.022). All but 2 survivors with severe malaria and rigid erythrocytes received a blood transfusion restoring RCD. Reduced RCD may contribute to impaired microcirculatory flow and a fatal outcome in falciparum malaria. RCD can be improved by blood transfusion. Since severely reduced RCD has a strong predictive value for mortality, blood transfusion possibly improves disease outcome not only through its beneficial effect on anaemia but also on RCD.

Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study.

BACKGROUND: Seizures commonly complicate cerebral malaria and are associated with an increased risk of death and neurological sequelae. We undertook a randomised study to assess the efficacy of intramuscular phenobarbital in preventing seizures in childhood cerebral malaria. METHODS: Children with cerebral malaria admitted to one hospital in Kilifi, Kenya, were randomly assigned a single intramuscular dose of phenobarbital (20 mg/kg) or identical placebo. Clinical tolerance was assessed at the start of the trial, with particular reference to respiratory depression and hypotension. Seizures were timed and recorded, and treated in a standard way. Plasma phenobarbital concentrations were measured. Analyses were by intention to treat. FINDINGS: 440 children with cerebral malaria were admitted to the hospital; 100 were not recruited to the study. Of the remaining 340, 170 received phenobarbital and 170 placebo. The drug was adequately absorbed and well tolerated. Seizure frequency was significantly lower in the phenobarbital group than in the placebo group (18 [11%] vs 46 [27%] children had three or more seizures of any duration; odds ratio 0.32 [95% CI 0.18-0.58]) but mortality was doubled (30 [18%] vs 14 [8%] deaths; 2.39 [1.28-4.64]). The frequency of respiratory arrest was higher in the phenobarbital group than in the placebo group, and mortality was greatly increased in children who received phenobarbital plus three or more doses of diazepam (odds ratio 31.7 [1.2-814]). INTERPRETATION: In children with cerebral malaria, phenobarbital 20 mg/kg provides highly effective seizure prophylaxis but is associated with an unacceptable increase in mortality. Use of this dose cannot, therefore, be recommended.

PIP: This randomized, placebo-controlled study assesses whether a single intramuscular dose of phenobarbital (20 mg/kg) given on admission to Kenyan children with cerebral malaria could lower the frequency of seizures, which complicate cerebral malaria by increasing the risk of death and neurological sequelae. A total of 340 children with cerebral malaria were admitted to the hospital; 170 received phenobarbital and 170 received placebo. The drug was adequately absorbed and well tolerated. Findings revealed a significantly lower frequency of seizures in the phenobarbital group than in the placebo group (18 [11%] vs. 46 [27%] children had 3 or more seizures of any duration; odds ratio (OR), 0.32; 95% confidence interval (CI), 0.18-0.58). However, mortality was doubled (30 [18%] vs. 14 [8%] deaths; OR, 2.39; 95% CI, 1.28-4.64) in the phenobarbital group. In addition, the frequency of respiratory arrest was higher in the phenobarbital group than in the placebo group, and mortality was greatly increased in children who received phenobarbital plus 3 or more doses of diazepam. In conclusion, although the phenobarbital dose of 20 mg/kg given to children with cerebral malaria provides highly effective seizure prophylaxis, an unacceptable increase in mortality is noted; hence, use of this dosage is not recommended.

Lactic acidosis and oxygen debt in African children with severe anaemia.

A syndrome of severe anaemia (Hb < or = 5 g/dl), particularly severe malarial anaemia (SMA), remains a major cause of childhood mortality in sub-Saharan Africa. We hypothesized that the lactic acidosis which identifies those at the greatest risk of death often represents an oxygen debt incurred as a result of inadequate tissue perfusion. To examine this hypothesis, we measured oxygen consumption (VO2) using a portable metabolic monitor. Blood lactate and acid-base status were also determined. Pre-transfusion data on 44 children (28 with mild symptoms, 7 with respiratory distress and 9 controls) demonstrated very close dependence of VO2 on body surface area (BSA, R2 = 0.86, p < 0.001). After correcting for BSA, no significant differences were observed in mean VO2 values of the three clinical groups, indicating that a critical reduction in oxygen delivery is not the sole explanation for the development of a lactic acidosis and severe symptoms. Nine children (including five of the original 44) were monitored during transfusion. In four of the five with SMA, severe symptoms and severe lactic acidosis, transfusion produced a marked, transient increase in VO2 (maximum 30-41%), with a marked fall in blood lactate and clinical improvement. These data suggest that some children with SMA and respiratory distress accumulate an oxygen debt when a relatively high oxygen demand outstrips supply, this debt being repaid when supply is increased during transfusion. However, in the remaining one of these five children, an increase in VO2 (maximum 20%), was accompanied by a rise in blood lactate and clinical deterioration, suggesting that more pathophysiologically complex mechanisms, which may predominate in some children.

PIP: A syndrome of severe anaemia (Hb or= 5 g/dl), particularly severe malarial anaemia (SMA), remains a major cause of childhood mortality in sub-Saharan Africa. The authors hypothesized that the lactic acidosis which identifies those at the greatest risk of death often represents an oxygen debt incurred as a result of inadequate tissue perfusion. To examine this hypothesis, the authors measured oxygen consumption (VO2) using a portable metabolic monitor. Blood lactate and acid-base status were also determined. Pre-transfusion data on 44 children (28 with mild symptoms, 7 with respiratory distress, and 9 controls) demonstrated very close dependence of VO2 on body surface area (BSA, R2 = 0.86, p 0.001). After correcting for BSA, no significant differences were observed in mean VO2 values of the three clinical groups, indicating that a critical reduction in oxygen delivery is not the sole explanation for the development of a lactic acidosis and severe symptoms. 9 children (including 5 of the original 44) were monitored during transfusion. In 4 of the 5 children with SMA, severe symptoms, and severe lactic acidosis, transfusion produced a marked, transient increase in VO2 (maximum 30-41%), with a marked fall in blood lactate and clinical improvement. These data suggest that some children with SMA and respiratory distress accumulate an oxygen debt when a relatively high oxygen demand outstrips supply, this debt being repaid when supply is increased during transfusion. However, in the remaining one of these 5 children, an increase in VO2 (maximum 20%) was accompanied by a rise in blood lactate and clinical deterioration, suggesting more pathophysiologically complex mechanisms, which may predominate in some children.