Randomized trial of volume expansion with albumin or saline in children with severe malaria: preliminary evidence of albumin benefit. Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial. Controlled trial of bicarbonate therapy in high-risk premature newborn infants. Mortality after fluid bolus in African children with severe infection. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Effectiveness of intravenous ephedrine infusion during spinal anaesthesia for caesarean section based on maternal hypotension, neonatal acid-base status and lactate levels. A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term newborn infants with hypoxic respiratory failure. Prophylactic ephedrine and hypotension associated with spinal anesthesia for cesarean delivery. Is continuous infusion ceftriaxone better than once-a-day dosing in intensive care? A randomized controlled pilot study.
Metabolic acidosis is the best predictor of death in children with severe falciparum malaria; however, its treatment presents a therapeutic dilemma, because acidosis and hypovolemia may coexist with coma, which can be associated with elevated intracranial pressure. We postulated that volume resuscitation with albumin might correct acidosis and hypovolemia with a lower risk of precipitating cerebral edema than crystalloid. In an open-label, randomized, controlled trial, we compared the safety of resuscitation with albumin to saline in Kenyan children with severe malaria.
                We randomly assigned children with severe malaria and metabolic acidosis (base deficit, >8 mmol/L) to receive fluid resuscitation with either 4.5% albumin or normal saline. A control (maintenance only) group was only included for patients with a base deficit of <15 mmol/L. The primary outcome measure was the percentage reduction in base deficit at 8 h. Secondary end points included death, the requirement for rescue therapies, and neurological sequelae in survivors.
                Of 150 children recruited for the trial, 61 received saline, 56 received albumin, and 33 served as control subjects. There was no significant difference in the resolution of acidosis between the groups; however, the mortality rate was significantly lower among patients who received albumin (3.6% [2 of 56 patients]) than among those who received saline (18% [11 of 61]; relative risk, 5.5; 95% confidence interval, 1.2-24.8; P=.013).
                In high-risk children with severe malaria and acidosis, fluid resuscitation with albumin may reduce mortality. Our study design did not enable us to determine whether saline administration is preferable to fluid restriction or whether saline administration is actually hazardous. Further studies are needed to confirm our findings before definitive treatment recommendations can be made. We conducted a controlled, prospective trial to evaluate the effectiveness of rapidly infusing sodium bicarbonate (NaHCO3) and salt-poor albumin into high-risk, premature infants in the first 2 hours of life. Fifty-three infants, randomized into one of four treatment groups, received 8 ml. per kilogram of a solution containing either (A) glucose in water, (B) salt-poor albumin, (C) NaHCO3, or (D) a combination of albumin and NaHCO3. After the initial infusion, the babies received no colloid or alkali solutions until 4 hours of age. We managed them supportively with warmth, appropriate oxygen administration, isotonic fluid infusion, and close monitoring. Among the infants who received alkali, 14 of 26 acquired the respiratory distress syndrome (RDS), 11 died, and four had intracranial hemorrhage. Among babies who received no alkali, RDS occurred in 11 of 27, 5 died, and none had intracranial hemorrhage. These results do not support the common practice of rapidly infusing NaHCO3 into high-risk, premature infants, and they suggest that the early management of such infants needs renewed critical evaluation. Sixty-two high-risk acidemic premature newborn infants, given maintenance intravascular infusions of 10% glucose, were assigned to liberal or restricted sodium bicarbonate treatment groups. Those infants in the liberal group received 5 to 15 mEq bicarbonate/dl 10% glucose, depending on the degree of acidosis. Among infants given bicarbonate, correction of pH was not more rapid and mortality was not decreased. Instead, there was a small increase in the number of deaths, but the incidence of intraventricular hemorrhage was similar to that in infants not given bicarbonate. The role of fluid resuscitation in the treatment of children with shock and life-threatening infections who live in resource-limited settings is not established.
                We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B). All children received appropriate antimicrobial treatment, intravenous maintenance fluids, and supportive care, according to guidelines. Children with malnutrition or gastroenteritis were excluded. The primary end point was 48-hour mortality; secondary end points included pulmonary edema, increased intracranial pressure, and mortality or neurologic sequelae at 4 weeks.
                The data and safety monitoring committee recommended halting recruitment after 3141 of the projected 3600 children in stratum A were enrolled. Malaria status (57% overall) and clinical severity were similar across groups. The 48-hour mortality was 10.6% (111 of 1050 children), 10.5% (110 of 1047 children), and 7.3% (76 of 1044 children) in the albumin-bolus, saline-bolus, and control groups, respectively (relative risk for saline bolus vs. control, 1.44; 95% confidence interval [CI], 1.09 to 1.90; P=0.01; relative risk for albumin bolus vs. saline bolus, 1.01; 95% CI, 0.78 to 1.29; P=0.96; and relative risk for any bolus vs. control, 1.45; 95% CI, 1.13 to 1.86; P=0.003). The 4-week mortality was 12.2%, 12.0%, and 8.7% in the three groups, respectively (P=0.004 for the comparison of bolus with control). Neurologic sequelae occurred in 2.2%, 1.9%, and 2.0% of the children in the respective groups (P=0.92), and pulmonary edema or increased intracranial pressure occurred in 2.6%, 2.2%, and 1.7% (P=0.17), respectively. In stratum B, 69% of the children (9 of 13) in the albumin-bolus group and 56% (9 of 16) in the saline-bolus group died (P=0.45). The results were consistent across centers and across subgroups according to the severity of shock and status with respect to malaria, coma, sepsis, acidosis, and severe anemia.
                Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa. (Funded by the Medical Research Council, United Kingdom; FEAST Current Controlled Trials number, ISRCTN69856593.). We evaluated the efficacy of probiotics in reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants.
                A prospective, masked, randomized control trial was conducted to evaluate the beneficial effects of probiotics in reducing the incidence and severity of NEC among VLBW (<1500 g) infants. VLBW infants who started to fed enterally and survived beyond the seventh day after birth were eligible for the trial. They were randomized into 2 groups after parental informed consents were obtained. The infants in the study group were fed with Infloran (Lactobacillus acidophilus and Bifidobacterium infantis) with breast milk twice daily until discharged. Infants in the control group were fed with breast milk alone. The clinicians caring for the infants were blinded to the group assignment. The primary outcome was death or NEC (>or= stage 2).
                Three hundred sixty-seven infants were enrolled: 180 in the study group and 187 in the control group. The demographic and clinical variables were similar in both groups. The incidence of death or NEC (>or= stage 2) was significantly lower in the study group (9 of 180 vs 24 of 187). The incidence of NEC (>or= stage 2) was also significantly lower in the study when compared with the control group (2 of 180 vs 10 of 187). There were 6 cases of severe NEC (Bell stage 3) in the control group and none in the study group. None of the positive blood culture grew Lactobacillus or Bifidobacterium species.
                Infloran as probiotics fed enterally with breast milk reduces the incidence and severity of NEC in VLBW infants. Maternal cardiovascular changes and neonatal acid-base status, including lactate levels, were assessed in 30 healthy women undergoing elective caesarean section under spinal anaesthesia. Patients were allocated randomly to receive IV ephedrine infusion (n = 15) (5 mg.min(-1) immediately after the spinal injection or bolus administration of IV ephedrine (n = 15) (10 mg) in case of development of hypotension. Maternal and neonatal blood pressure, heart rate and acid-base status including lactate levels were compared between the groups. Systolic blood pressure in the bolus group was significantly lower when compared to the infusion group. Nausea was observed in one patient (6%) in the infusion group and nausea and vomiting were observed in 10 patients (66%) in the bolus group. Although umbilical arterial pH values were significantly lower in the bolus group, lactate levels were similar In conclusion, ephedrine infusion prevented maternal hypotension, reduced the incidence of nausea and vomiting and led to improved umbilical blood pH during spinal anaesthesia for caesarean section. Inhaled nitric oxide (iNO) reduces the use of extracorporeal membrane oxygenation (ECMO)/incidence of death in term and near-term neonates with severe hypoxic respiratory failure. We conducted a randomized, double masked, multicenter trial to determine whether administration of iNO earlier in respiratory failure results in additional reduction in the incidence of these outcomes.
                Neonates who were born at > or =34 weeks' gestation were enrolled when they required assisted ventilation and had an oxygenation index (OI) > or =15 and <25 on any 2 measurements in a 12-hour interval. Infants were randomized to early iNO or to simulated initiation of iNO (control). Infants who had an increase in OI to 25 or more were given iNO as standard therapy.
                The trial enrollment was halted after 75% of target sample size was reached because of decreasing availability of eligible patients. The 150 infants who were given early iNO and 149 control infants had similar baseline characteristics. Arterial oxygen tension increased by >20 mm Hg in 73% of early iNO and 37% of control infants after study gas initiation. Control infants received standard iNO and deteriorated to OI >40 more often than infants who were given early iNO. The incidence of death (early iNO, 6.7% vs control, 9.4%), ECMO (10.7% vs 12.1%), and their combined incidence (16.7% vs 19.5%) were similar in both groups.
                iNO improves oxygenation but does not reduce the incidence of ECMO/mortality when initiated at an OI of 15 to 25 compared with initiation at >25 in term and near-term neonates with respiratory failure. Hypotension commonly accompanies induction of spinal anesthesia for cesarean section. To determine whether intravenous ephedrine prophylaxis would benefit prehydrated obstetrical patients presenting for elective cesarean section, we studied 30 patients randomly assigned to one of three experimental groups. All patients were preloaded with crystalloid (15 ml/kg), given spinal anesthesia and positioned with left uterine displacement (LUD). During induction, all patients received a 2 ml intravenous bolus and intravenous infusion of the study drug or placebo. The control group (n=10) received a saline bolus and saline infusion, the bolus group (n=10) received an ephedrine bolus (10 mg) and a saline infusion and the infusion group (n=10) received a saline bolus and a two-stage ephedrine infusion (20 mg over 12 min). After induction of anesthesia, systolic blood pressure decreased in the first 5 min in all groups. Hypotension occurred in 6/10 control patients, 5/10 bolus patients and 5/10 infusion patients. The amount of supplemental ephedrine required to treat hypotension did not differ among groups. Although the efficacy of ephedrine prophylaxis for hypotension associated with spinal anesthesia for elective cesarean section cannot be established by the small number of patients studied, this practice does not appear to be clinically relevant at the doses studied. To compare the clinical and bacteriological outcome of critically ill patients with sepsis treated by ceftriaxone administered as a once-a-day intermittent bolus dose or by 24 h continuous infusion.
                We conducted an open-label, randomized controlled pilot study in 57 patients clinically diagnosed with sepsis (suspected/proven infection and systemic inflammatory response syndrome) in a tertiary level intensive care unit. Patients were randomized to receive 2 g of ceftriaxone administered by once-daily intermittent bolus dosing or by 24 h continuous infusion. Clinical and bacteriological outcomes were assessed by blinded clinicians.
                Fifty-seven patients were enrolled in the study, 50 of whom fulfilled the a priori definition of treatment for 4 or more days. The infusion (n = 29) and bolus groups (n = 28) were similar in terms of demographics, although the median age of those receiving the infusion was younger. Intention-to-treat analysis found no statistically significant differences in the primary outcomes for clinical response (P = 0.17), clinical cure [infusion n = 13/29 versus bolus n = 5/28; adjusted odds ratio (AOR) = 3.74; 95% confidence interval (95% CI) = 1.11-12.57; P = 0.06], bacteriological response (P = 0.41) and bacteriological cure (infusion n = 18/29 versus bolus 14/28; AOR = 1.64; 95% CI = 0.57-4.70; P = 0.52). However, logistic regression in patients that complied with the a priori definitions who received ceftriaxone by continuous infusion (AOR = 22.8; 95% CI = 2.24-232.3; P = 0.008) or patients with a low Acute Physiology and Chronic Health Evaluation (APACHE) II score (AOR = 0.70; 95% CI = 0.54-0.91; P = 0.008) were associated with an improved clinical outcome when age and Sepsis Organ Failure Assessment (SOFA) score at time of study entry were controlled for.
                This pilot study suggests clinical and bacteriological advantages of continuous infusion of ceftriaxone over bolus administration in critically ill patients in patients requiring 4 or more days of treatment. This sets the scene for a large multicentre double-blind randomized controlled trial to confirm these findings.
There is insufficient evidence from randomised controlled trials to determine whether infusion of base or fluid bolus reduces morbidity and mortality in preterm infants with metabolic acidosis. Further large randomised trials are needed.