Early Goal-Directed Therapy With and Without Intermittent Superior Vena Cava Oxygen Saturation Monitoring in Pediatric Septic Shock: A Randomized Controlled Trial.

OBJECTIVE: To compare early goal-directed therapy (EGDT) 'with' and 'without' intermittent superior vena cava oxygen saturation (ScvO2) monitoring in pediatric septic shock. DESIGN: Open label randomized controlled trial. SETTING: Pediatric intensive care unit in a tertiary care center. PARTICIPANTS: Children aged 1 month to 12 year with septic shock. INTERVENTION: Patients not responding to fluid resuscitation (up to 40 mL/kg) were randomized to EGDT 'with' (n=59) and 'without' (n=61) ScvO2 groups. Resuscitation was guided by ScvO2 monitoring at 1-hour, 3-hour, and later on six-hourly in the 'with' ScvO2 group, and by clinical variables in the 'without' ScvO2 group. OUTCOME: Primary outcome was all-cause 28-day mortality. Secondary outcomes were time to and proportion of patients achieving therapeutic endpoints (at 6 hours and PICU stay), need for organ supports, new organ dysfunction (at 24 hours and PICU stay), and length of PICU and hospital stay. RESULTS: The study was stopped after interim analysis due to lower mortality in the intervention group. There was significantly lower all-cause 28-day mortality in EDGT with ScvO2 than without ScvO2 group [37.3% vs. 57.5%, adjusted hazard ratio 0.57, 95%CI 0.33 to 0.97, P=0.04]. Therapeutic endpoints were achieved early in 'with' ScvO2 group [mean (SD) 3.6 (1.6) vs. 4.2 (1.6) h, P=0.03]. Organ dysfunction by sequential organ assessment score during PICU stay was lower in 'with' ScvO2 group [median (IQR) 5 (2,11) vs. 8 (3,13); P=0.03]. There was no significant difference in other secondary outcomes. CONCLUSIONS: EGDT with intermittent ScvO2 monitoring was associated with reduced mortality and improved organ dysfunction in pediatric septic shock.

Low-Dose (0.05 Unit/kg/hour) vs Standard-Dose (0.1 Unit/kg/hour) Insulin in the Management of Pediatric Diabetic Ketoacidosis: A Randomized Double-Blind Controlled Trial.

OBJECTIVE: To compare the efficacy of insulin infusion of 0.05 Unit/kg/hour vs 0.1 Unit/kg/hour in the management of pediatric diabetic ketoacidosis (DKA). DESIGN: Randomized, double-blind controlled clinical trial. SUBJECT: Pediatric critical care division of a tertiary care hospital from October, 2014 to July, 2018. PARTICIPANTS: Children aged 12 years or younger with a diagnosis of DKA. Children with septic shock and those who had received insulin before enrollment were excluded. INTERVENTION: Low-dose (0.05 Unit/kg/hour) vs. Standard-dose (0.1 Unit/kg/hour) insulin infusion. OUTCOME MEASURES: The primary endpoint was time for resolution of DKA (pH ≥7.3, bicarbonate ≥15 mEq/L, beta-hydroxybutyrate <1 mmol/L). Secondary outcomes were the rate of fall in blood glucose until 250 mg/dL or less and the rate of complications (hypokalemia, hypoglycemia, and cerebral edema). RESULTS: Sixty patients were analyzed on an intention-to-treat basis (Low-dose group: n=30; Standard-dose group: n=30). Mean (SD) time taken for the resolution of ketoacidosis was similar in both groups [22 (12) vs 23 (18.5) hours; P=0.92]. The adjusted hazard ratio (95% CI) of the resolution of ketoacidosis was lower in the low-dose group [0.40 (0.19 to 0.85); P=0.017]. Mean (SD) rate of blood glucose decrease until 250 mg/dL or less reached [56 (41) vs 64 (65) mg/dL/hour; P=0.41] and time to achieve the target [4.2 (3.1) vs 4.8 (3.3) hours; P=0.44] were similar in both groups. Hypokalemia [30% vs 43.3%; P=0.28] and hypoglycemia [3.3% vs 13.3%; P=0.35] were lower in low-dose group. No child had cerebral edema, and no mortality occurred. CONCLUSIONS: Time for resolution of ketoacidosis was similar in the low-dose and standard-dose insulin with a lower rate of therapy-related complications in the low-dose group. Hence, low-dose insulin infusion can be a safer approach in the management of pediatric DKA.

Capillary versus Serum b-hydroxybutyrate in Pediatric Diabetic Ketoacidosis.

OBJECTIVE: To find the strength of agreement between point-of-care and serum b-hydroxybutyrate. METHODS: 236 paired samples (capillary b-hydroxybutyrate by a point of care device and serum b-hydroxybutyrate by colorimetric enzymatic estimation) samples were collected from 26 children aged <13 years admitted with diabetic ketoacidosis. Inborn errors of metabolism and septic shock were excluded. RESULTS: Capillary b-hydroxybutyrate showed excellent agreement with serum â-hydroxybutyrate with mean (SD) bias of 0.027 (0.78); 95% limit of agreement -1.51, 1.56 and intraclass correlation 96.1% (95%CI 95%-97%, P<0.001). An increase in the bias noted for value above 5 mmol/L (P<0.001) (serum measurements were higher than capillary point-of-care measure-ments). Capillary â-hydroxybutyrate correlated significantly with blood pH, anion gap,bicarbonate and carbon dioxide levels on blood gas analysis (P<0.05). CONCLUSIONS: Capillary b-hydroxybutyrate estimation is a valid method for monitoring of ketonemia in pediatric diabetic ketoacidosis.

Second Dose of Scorpion Antivenom in Children with Indian Red Scorpion (Mesobuthus tamulus) Sting Envenomation.

OBJECTIVE: To study the effect of the second dose of scorpion antivenom in children with non-resolving or worsening scorpion sting envenomation. METHODS: 72 children aged ≤12 years with scorpion sting envenomation grade 2 and above were enrolled. 61 received the first dose of three vials of antivenom at admission (group A). Children with persistent/worsening envenomation at 6 hours received the second dose (group B). The time required for resolution of autonomic symptoms, myocardial dysfunction, predictors of the second dose and side effects were studied. RESULTS: The mean time taken for resolution of autonomic symptoms were similar in GroupA and B (4.1 vs. 5.3 hours, P=0.452), and of myocardial dysfunction was shorter in Group A (10.8 vs. 37.6 hours, P=0.019). On regression analysis, abnormal echocardiography at admission was found to be a significant predictor of the second dose (OR=27.6, 95% CI, 4.7-162.5; P=<0.001). CONCLUSION: Children with severe scorpion sting envenomation with abnormal echocardiography may require a higher dose of scorpion antivenom.

Histopathological changes in septic acute kidney injury in critically ill children: a cohort of post-mortem renal biopsies.

BACKGROUND: Septic acute kidney injury (AKI) accounts for more than half of all cases of AKI in critically ill children. The renal histology was found to alter the management in more than two-third of cases of adult acute renal failure. Better insight into the pathogenesis of pediatric septic AKI could be based on developing a clearer appreciation of the histopathological changes. No comprehensive study of the histopathological features of septic AKI in critically ill children has yet been performed. METHODS: This retrospective observational study was conducted at a level-III pediatric intensive care unit (PICU) from June 2013 to July 2014. Children (<13 years of age) who had expired due to sepsis and AKI and had post-mortem renal biopsies were included. Sepsis and AKI were defined according to the International pediatric sepsis consensus conference and Acute Kidney Injury Network (AKIN) definition and classification system, respectively. RESULTS: A total of 708 patients were admitted to the PICU during the study period, with mortality of 24 % (n = 170) and 62 complete data of post-mortem renal biopsies were included. The median (IQR) age was 12 (4.8-36) months, pediatric risk of mortality score (PRISM) III was 14 (12-18) and the time to biopsy after death was 24 (18-26) minutes. Normal histology was the most common change 41.9 % (n = 26), followed by acute tubular necrosis (ATN) 30.6 % (n = 19). A combination of changes involving tubules, glomeruli, interstitium, and blood vessels was noted in 21 % (n = 13) of the specimens. Eight percent (n = 5) of the specimens had features consistent with thrombotic microangiopathy. Normal histology was noted in 15.4 % (n = 4/26), 50 % (n = 13/26), and 34.6 % (n = 9/26) of AKI stage-I, II, and III, respectively. CONCLUSION: The most common renal histopathological change in septic AKI in critically ill children was normal histology followed by ATN.