M. Jayashree

Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus.

The objective of this study was to compare the efficacy of continuous midazolam and diazepam infusion for the control of refractory status epilepticus. An open-label, randomized control study was undertaken at the Pediatric Emergency and Intensive Care Service of a multidisciplinary teaching and referral hospital. Subjects included 40 children, 2 to 12 years of age, with refractory status epilepticus (motor seizures uncontrolled after two doses of diazepam, 0.3 mg/kg per dose, and phenytoin infusion, 20 mg/kg). Either continuous midazolam (n = 21) or diazepam infusion (n = 19) in incremental doses was administered. The primary outcome measure was the proportion of children in each group with successful control of refractory status epilepticus. The secondary outcome measure was the time to control seizure activity, recurrence of seizure after initial control, if any, the frequency of hypotension, and the need for ventilation. The two groups were similar in age (mean ± SD = 4.9 ± 43.6 months) and etiology. Twenty-three (57.5%) patients had acute central nervous system infection. Refractory status epilepticus was controlled in 18 (86%) and 17 (89%) patients in the midazolam and diazepam groups, respectively (P = not significant). The median time to seizure control was 16 minutes in both groups, but in the midazolam group, seizures recurred in more children (57% versus 16% in diazepam group; P < .05). The maximum dose (mean ± SD) of midazolam and diazepam required was 5.3 ± 2.6 μg/kg/min and 0.04 ± 0.02 mg/kg/min, respectively. About half of the patients needed mechanical ventilation and 40% had hypotension in both groups, but the mortality was higher in the midazolam group (38%) as compared to the diazepam group (10.5%, P < . 1 > .05). Continuous midazolam and diazepam infusions were equally effective for control of refractory status epilepticus. However, midazolam was associated with more seizure recurrence and higher mortality in refractory status epilepticus predominantly caused by central nervous system infections. (J Child Neurol 2002;17:106-110).

Diabetic ketoacidosis: predictors of outcome in a pediatric intensive care unit of a developing country.

Objectives: To study the outcome and predictors of mortality in children with diabetic ketoacidosis. Design: Retrospective case series. Setting: Pediatric intensive care unit of an urban multiple-specialty teaching and referral hospital in north India. Patients: Sixty-eight patients with diabetic ketoacidosis treated between 1993 and 2000. Interventions: Data were retrieved from case records with respect to patients’ age; clinical features; osmolality at admission; blood glucose, serum potassium, and arterial pH at admission, 6 hrs, and 24 hrs; complications during the course of hospital stay; treatment; and outcome in terms of survival or death. Survivors and nonsurvivors were compared to determine the predictors of mortality. Measurements and Main Results: The mean (sd) age of the study population was 6.9 (3.5) yrs (range, 0.5–12 yrs). Impaired consciousness (n = 45; 66%), rapid breathing (n = 41; 60%), and vomiting (n = 35; 51.4%) were common presenting symptoms. Thirty-two (50%) patients had clinically evident dehydration. Precipitating events identified were new-onset diabetes with sepsis (37%), new-onset diabetes alone (31%), insulin omission (15%), and infection with insulin omission (7%). The mean (sd) blood glucose, osmolality, and pH at admission were 473 (sd 184) mg/dL, 305 (sd 24) mOsm/L, and 7.08 (sd 0.1), respectively. Complications noted during treatment were hypokalemia (n = 28; 41%), hypoglycemia (n = 10; 15%), cerebral edema (n = 9; 13.2%), and pulmonary edema (n = 2; 3%). Nine (13.2%) patient died, with the causes of death being septic shock (n = 4), cerebral edema (n = 2), cerebral edema with pulmonary edema (n = 2), and hypokalemia with ventricular tachycardia (n = 1). Those who died were older, had higher osmolality and severe acidosis at admission, and had persistent hyperglycemia and acidosis at 6–12 hrs. On multiple logistic regression analysis, osmolality at admission was the most significant predictor of death. Conclusions: Two thirds of children with diabetic ketoacidosis in our series had new-onset diabetes, and 13.2% died. Serum osmolality at admission was the most important predictor of death.

Low-dose hydrocortisone in pediatric septic shock: an exploratory study in a third world setting.

Objective: To study the efficacy of low-dose intravenous hydrocortisone therapy in the management of pediatric septic shock with respect to the time taken for shock reversal and requirement of inotropes. Design: Open label randomized pilot study. Setting: Pediatric intensive care unit of a tertiary care pediatric center in a third world country. Patients: Thirty-eight children, 2 months–12 yrs of age, with septic shock unresponsive to fluid therapy alone. Intervention: Intravenous hydrocortisone 5 mg/kg/day in four divided doses followed by half the dose for a total duration of 7 days or normal saline (similar amount in a similar manner) for the same duration. Results: There was a trend toward earlier reversal of shock (median 49.5 vs. 70 hrs, p = 0.65, Mann-Whitney U test) and lower inotropes requirement (median {lsqb;10th–90th centile{rsqb; inotropes score: 20 {lsqb;15–60{rsqb; vs. 50 {lsqb;20–80{rsqb;, p = 0.15) in the hydrocortisone-treated patients as compared with controls, although the difference was not statistically significant. Mortality rate was similar in both groups. Conclusions: Our data, although, inconclusive favor the need for a study with a larger sample size to clearly define role of low-dose hydrocortisone in pediatric septic shock in developing countries, while taking in consideration effect of malnutrition, delayed presentations, and their interactions with the hypothalamic-pituitary-adrenocortical axis.

Low-Dose vs Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis A Randomized Clinical Trial

IMPORTANCE The standard recommended dose (0.1 U/kg per hour) of insulin in diabetic ketoacidosis (DKA) guidelines is not backed by strong clinical evidence. Physiologic dose-effect studies have found that even lower doses could adequately normalize ketonemia and acidosis. Lowering the insulin dose may be advantageous in the initial hours of therapy when a gradual decrease in glucose, electrolytes, and resultant osmolality is desired. OBJECTIVE To compare the efficacy and safety of low-dose insulin against the standard dose in children with DKA. DESIGN, SETTING, AND PARTICIPANTS This was a prospective, open-label randomized clinical trial conducted in the pediatric emergency department and intensive care unit of a tertiary care teaching hospital in northern India from November 1, 2011, through December 31, 2012. A total of 50 consecutive children 12 years or younger with a diagnosis of DKA were randomized to low-dose (n = 25) and standard-dose (n = 25) groups. INTERVENTIONS Low-dose (0.05 U/kg per hour) vs standard-dose (0.1 U/kg per hour) insulin infusion. MAIN OUTCOMES AND MEASURES The primary outcome was the rate of decrease in blood glucose until a level of 250 mg/dL or less is reached (to convert to millimoles per liter, multiply by 0.0555). The secondary outcomes included time to resolution of acidosis, episodes of treatment failures, and incidences of hypokalemia and hypoglycemia. RESULTS The mean (SD) rate of blood glucose decrease until a level of 250 mg/dL or less is reached (45.1 [17.6] vs 52.2 [23.4] mg/dL/h) and the mean (SD) time taken to achieve this target (6.0 [3.3] vs 6.2 [2.2] hours) were similar in the low- and standard-dose groups, respectively. Mean (SD) length of time to achieve resolution of acidosis (low vs standard dose: 16.5 [7.2] vs 17.2 [7.7] hours; P = .73) and rate of resolution of acidosis were also similar in the groups. Hypokalemia was seen in 12 children (48%) receiving the standard dose vs 5 (20%) of those receiving the low dose (P = .07); the tendency was more pronounced in malnourished children (7 [88%] vs 2 [28%]). Five children (20%) and 1 child (4%) receiving standard- and low-dose infusion (P = .17), respectively, developed hypoglycemia. Treatment failure was rare and comparable. One child in the standard-dose group developed cerebral edema, and no deaths occurred during the study period. CONCLUSIONS AND RELEVANCE Low dose is noninferior to standard dose with respect to rate of blood glucose decrease and resolution of acidosis. We advocate a superiority trial with a larger sample size before 0.05 U/kg per hour replaces 0.1 U/kg per hour in the practice recommendations. TRIAL REGISTRATION ctri.nic.in Identifier: CTRI/2012/04/002548.

Randomized controlled trial comparing cerebral perfusion pressure-targeted therapy versus intracranial pressure-targeted therapy for raised intracranial pressure due to acute CNS infections in children.

Objective:In children with acute CNS infection, management of raised intracranial pressure improves mortality and neuromorbidity. We compared cerebral perfusion pressure–targeted approach with the conventional intracranial pressure–targeted approach to treat raised intracranial pressure in these children. Design:Prospective open-label randomized controlled trial. Setting:PICU in a tertiary care academic institute. Patients:Hundred ten children (1–12 yr) with acute CNS infections having raised intracranial pressure and a modified Glasgow Coma Scale score less than or equal to 8 were enrolled. Interventions:Patients were randomized to receive either cerebral perfusion pressure–targeted therapy (n = 55) (maintaining cerebral perfusion pressure ≥ 60 mm Hg, using normal saline bolus and vasoactive therapy—dopamine, and if needed noradrenaline) or intracranial pressure–targeted therapy (n = 55) (maintaining intracranial pressure < 20 mm Hg using osmotherapy while ensuring normal blood pressure). The primary outcome was mortality up to 90 days after discharge from PICU. Secondary outcome was modified Glasgow Coma Scale score at 72 hours after enrollment, length of PICU stay, duration of mechanical ventilation, and hearing deficit and functional neurodisability at discharge and 90-day follow-up. Measurements and Main Results:A 90-day mortality in intracranial pressure group (38.2%) was significantly higher than cerebral perfusion pressure group (18.2%; relative risk = 2.1; 95% CI, 1.09–4.04; p = 0.020). The cerebral perfusion pressure group in comparison with intracranial pressure group had significantly higher median (interquartile range) modified Glasgow Coma Scale score at 72 hours (10 [8–11] vs 7 [4–9], p < 0.001), shorter length of PICU stay (13 d [10.8–15.2 d] vs 18 d [14.5–21.5 d], p = 0.002) and mechanical ventilation (7.5 d [5.4–9.6 d] vs 11.5 d [9.5–13.5 d], p = 0.003), lower prevalence of hearing deficit (8.9% vs 37.1%; relative risk = 0.69; 95% CI, 0.53–0.90; p = 0.005), and neurodisability at discharge from PICU (53.3% vs 82.9%; relative risk = 0.37; 95% CI, 0.17–0.81; p = 0.005) and 90 days after discharge (37.8% vs 70.6%; relative risk = 0.47; 95% CI, 0.27–0.83; p = 0.004). Conclusion:Cerebral perfusion pressure–targeted therapy, which relied on more frequent use of vasopressors and lesser use of hyperventilation and osmotherapy, was superior to intracranial pressure–targeted therapy for management of raised intracranial pressure in children with acute CNS infection in reducing mortality and morbidity.

Changing Trends and Predictors of Outcome in Patients with Acute Poisoning Admitted to the Intensive Care

BACKGROUND Acute poisoning in children is a medical emergency and preventable cause of morbidity and mortality. Knowledge about the nature, magnitude, outcome and predictors of outcome is necessary for management and allocation of scant resources. METHODS This is a retrospective study conducted in the Pediatric Intensive Care Unit (PICU) of an urban multi speciality teaching and referral hospital in North India from January 1993 to June 2008 to determine the epidemiology, clinical profile, outcome and predictors of outcome in children with acute poisoning. Data of 225 children with acute poisoning was retrieved from case records with respect to demographic profile, time to presentation, PRISM score, clinical features, investigations, therapeutic measures, complications and outcome in terms of survival or death. Survivors and non-survivors were compared to determine the predictors of mortality. RESULTS Acute poisoning constituted 3.9% of total PICU admissions; almost all (96.9%) were accidental. The mean age of study patients was 3.3 ± 3.1 (range 0.10-12) years with majority (61.3%) being toddlers (1-3 years). In the overall cohort, kerosene (27.1%) and prescription drugs (26.7%) were the most common causative agents followed by organophosphates (16.0%), corrosives (7.6%), carbamates (4.9%) and aluminum phosphide (4.9%). However the trends of the three 5-year interval (1993 till the end of 1997, 1998 till the end of 2002 and 2003 till the end of June 2008) revealed a significant decrease in kerosene, aluminum phosphide and iron with increase in organophosphate compound poisoning. Ninety nine (44%) patients required supplemental oxygen, of which nearly half (n = 42; 42.4%) needed mechanical ventilation. Twenty (8.9%) died; cause of death being iron poisoning in five; aluminum phosphide in four; organophosphates in three and one each because of kerosene, diesel, carbamate, corrosive, sewing machine lubricant, isoniazid, salicylate and maduramycin poisoning. There has been a significant decrease in the mortality over the years. The non-survivors were older, had a higher PRISM score and hypotension at admission and higher need for oxygen and ventilation. On multiple logistic regression analysis hypotension at admission was the most significant predictor of death (adjusted odds ratio: 5.59; 95% confidence interval: 1.38-22.63; p = 0.016). CONCLUSION Acute poisoning in children over the past 15 years has shown a changing trend with significant decrease in kerosene, iron and aluminum phosphide and an increase in organophosphate and prescription drugs. The overall mortality has decreased significantly. Hypotension at admission was the most significant predictor of death.

Cerebral Perfusion Pressure-Targeted Approach in Children With Central Nervous System Infections and Raised Intracranial Pressure: Is It Feasible?

This study was conducted to evaluate the feasibility of cerebral perfusion pressure—targeted therapy in children with raised intracranial pressure caused by central nervous system infection. A prospective observational pilot study was conducted in the pediatric intensive care unit of a tertiary care teaching hospital. Twenty children (ages 6 months to 12 years) with a clinical diagnosis of meningitis or meningoencephalitis were included. Intracranial pressure and blood pressure monitoring were initiated soon after enrollment. Interventions to reduce intracranial pressure and elevate blood pressure were used to achieve a target cerebral perfusion pressure of greater than 70 mm Hg in children 2 years of age or older and greater than 60 mm Hg in children less than 2 years. Therapies used to achieve target cerebral perfusion pressure were initial fluid boluses (in 14 patients), vasopressors (in 8), and mannitol (in 10). The target cerebral perfusion pressure was achieved in 6 patients, whereas a cerebral perfusion pressure greater than 50 mm Hg was achieved in 16 patients. All 4 patients with mean cerebral perfusion pressure less than 50 mm Hg died of intractable, raised intracranial pressure. In contrast, only 3 of 16 patients with mean cerebral perfusion pressure more than 50 mm Hg died. In children with raised intracranial pressure caused by central nervous system infection, it was feasible to achieve a cerebral perfusion pressure greater than 50 mm Hg, mainly by increasing the blood pressure within the first 24 hours and by reducing intracranial pressure after the first 24 hours.

Probiotic use and prevalence of candidemia and candiduria in a PICU.

Objectives: To compare the prevalence of candidemia and candiduria before and after the introduction of routine use of probiotics in children who received broad-spectrum antibiotics in a PICU. Design: Retrospective “before and after” study. Setting: A 12-bed PICU of a teaching hospital in India. Patients: Children 3 months to 12 years old, admitted to the PICU over two 9 months’ time periods, who received broad-spectrum antibiotics for more than 48 hours. Interventions: Three hundred forty-four patients enrolled between November 2008 and July 2009 after the introduction of routine use of probiotics served as the “probiotic group”; they had received one sachet twice a day of a probiotic mix (EUGI [Wallace Pharma, Goa, India] containing Lactobacillus acidophillus, Lactobacillus rhamnosum, Bifidobacterium longum, Bifidobacterium bifidum, Saccharomyces boulardii, and Streptococcus thermophilus) for 7 days. Three hundred seventy-six children enrolled between February 2007 and October 2007 served as “controls.” Blood was sent for bacterial and fungal cultures if clinically indicated and urine catheter/bag specimen was submitted for bacterial and fungal culture twice a week as per unit’s protocol. Measurements and Main Results: Primary outcome was growth of Candida in blood (candidemia), and secondary outcomes were growth of Candida in urine (candiduria), nosocomial bloodstream infections, and urinary tract infections. Data were retrieved from the case records. Candidemia was seen in four of 344 patients (1.2%) in the probiotic group and in 14 of 376 (3.7%) in the control group (relative risk, 0.31; 95% CI, 0.10–0.94; p = 0.03). Candiduria was noted in 37 of 344 patients (10.7%) in the probiotic group and 83 of 376 (22%) in the control group (relative risk, 0.48; 95% CI, 0.34–0.7; p = 0.0001). The prevalence of nosocomial bloodstream infection and urinary tract infection in the probiotic and control groups was 20.3% and 26% (p = 0.07) and 14.2% and 19.1% (p = 0.08), respectively. Conclusions: Routine use of a mix of probiotics in patients who receive broad-spectrum antibiotics could be a useful strategy to reduce the prevalence of candidemia and candiduria in the PICU.

Penicillin and gentamicin therapyvs amoxicillin/clavulanate in severe hypoxemic pneumonia

Objective: To compare the efficacy of sequential injectable crystalline penicillin (C.pen) and gentamicin combination followed by amoxicillin with sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe or very severe hypoxemic pneumonia.Methods: Children aged 2–59 months with WHO-defined severe or very severe pneumonia with hypoxemia (SpO2<90%) were included in the study. Patients with fever>10 days, bacterial meningitis, prior antibiotic therapy >24 hours, stridor, heart disease and allergy to any of the study drugs were excluded. They were randomly allocated to two groups—Group A and Group B. Group A received C. pen and gentamicin intravenously (IV), followed by oral amoxicillin and group B got amox-clav IV, followed by oral amox-clav. Minimum duration of IV therapy was 3 days and total 7 days. Respiratory rate, oxygen saturation and chest wall indrawing were monitored 6 hourly.Results: 71 patients were included. There were two (5.2%) blood cultures positive in group A and three (9%) in group B. Organisms isolated wereS. pneumoniae (n=3) andH. influenzae-b (n=2). There was only one treatment failure in each of the groups. One was due to penicillin resistantH. influenzae-b and the other was due to worsening of pneumonia. The mean time taken for normalization of tachypnea, hypoxia, chest wall indrawing and inability to feed was similar (P-N.S). Mean duration of IV therapy in group A was 76±25 hrs and group B was 75±24 hrs (p>0.1).Conclusion: In children of 2–59 months, sequential injectable C. pen and gentamicin combination, followed by oral amoxicillin or sequential IV and oral amox-clav were equally effective for the treatment of severe or very severe hypoxemic community acquired pneumonia.

Nutritional status and complications in children with diabetic ketoacidosis.

Objective: Diabetic ketoacidosis in children continues to be an important cause of morbidity and mortality, especially in developing economies as a result of malnutrition, a high rate of infections, and delay in seeking timely medical care. Malnutrition also increases the risk of diabetic ketoacidosis-related complications. The objective of this study was to assess the nutritional status of patients presenting with diabetic ketoacidosis and correlate it with the incidence of complications at presentation and those encountered during the course of illness. Design: Prospective study. Setting: Pediatric emergency and intensive care units, Advanced Pediatrics Centre, PGIMER, Chandigarh, India. Patients: Thirty-three children between 1 month and 12 yrs of age presenting with diabetic ketoacidosis between July 2008 and June 2009 were enrolled consecutively and assessed for nutritional status by anthropometric parameters (body weight, crown–heel length/height, mid–upper arm circumference, triceps and subscapular skin fold thicknesses), biochemical parameters (serum albumin, zinc, magnesium, vitamin A levels), and preillness dietary history (by pretested Food Frequency Questionnaire). Patients were classified as malnourished or normally nourished based on the weight for age criteria matched for Indian standards. The incidence of complications (electrolyte imbalances, hypoglycemia, sepsis, cerebral edema, etc.) and outcome in terms of survival or death in both the groups were compared with Student’s t-test for parametric data, Mann-Whitney U test for nonparametric data, and chi-square test for categorical variables. Interventions: None. Measurements and Main Results: Anthropometric assessment showed that 11 of 33 (33.3%) were malnourished. Preillness dietary history revealed that 16 (48.5%) were calorie- and protein-deficient (known diabetic n = 7; new onset n = 9), whereas 11 (33.3%) were only calorie-deficient (known diabetic n = 2). Hypoalbuminemia was seen in 21 (63.6%), hypovitaminosis A in eight (24.2%), and low zinc levels in three (9%). The malnourished and normally nourished groups were similar with respect to demographics, precipitating factors, severity of diabetic ketoacidosis, treatment received, and outcome. However, the incidence and severity of therapy-related hypokalemia (100% vs. 72.7%; p = .05) and hypoglycemia (63.6 vs. 13.6%; p = .004) were significantly higher in the former as compared with the latter. The mean ± SD admission serum potassium levels were similar in both the groups (3.4 ± 0.8 mEq/L in the malnourished vs. 3.5 ± 0.7 mEq/L in the normally nourished) with the malnourished group showing a significant fall at 6 hrs after start the of diabetic ketoacidosis protocol (2.8 ± 0.8 mEq/L vs. 3.6 ± 0.7 mEq/L; p = .033), although the mean rate and dose of insulin infusion were similar. The fall in blood glucose (mean ± SD mg/dL) at 12, 24, and 36 hrs after onset of the diabetic ketoacidosis protocol was also significantly greater in the malnourished group as compared with the normally nourished diabetic ketoacidosis (195 ± 69.1 and 272.61 ± 96.3, p = .02; 171 ± 58.5 and 257 ± 96.3, p = .05; and 153.75 ± 49.6 and 241.71 ± 76.3, p = .04, respectively). The incidence of hypophosphatemia, hypomagnesemia, cerebral edema, renal failure, sepsis, and septic shock was similar in both the groups. There were two deaths, both resulting from complicating cerebral edema and renal failure and unrelated to the nutritional status of the patients. Conclusions: The incidence and severity of therapy-related hypokalemia and hypoglycemia were significantly higher in the malnourished as compared to the normally nourished diabetic ketoacidosis. Other diabetic ketoacidosis-related complications and outcome were similar in both the groups.