Background

Usual dosing regimens of meropenem could lead to the suboptimal exposure in critically ill children

Objectives

We aimed to develop a meropenem population pharmacokinetic model and simulate dosing regimens in order to optimize patient exposure

Methods

Meropenem PK was investigated using a non linear mixed-effect modeling approach. Meropenem concentration was quantified by high performance liquid chromatography. Estimated glomerular filtration rate (eGFR) was estimated by the Schwartz formula

Results

Forty patients with a total of 121 samples were included. Eleven patients received continuous replacement renal therapy (CRRT). Concentration-time courses were best described by a two-compartment model with first order elimination. Bodyweight (BW), eGFR and CRRT were significant covariates inluencing clearance (CL), inter compartment clearance (Q) and central/peripheral volume of distribution (V1/V2):

V1_i= V1_pop x (BW/70)¹, Q_i = Q_popx (BW/70)^0.75, V2_i = V2_pop x(BW/70)¹ , CL_i= (CL_pop x (BW/70)^0.75) x (eGFR/151)^0.355) for patients without CRRT and CL_i = (CL_pop x (BW/70)^0.75) x 0.8 for patients with CRRT.

Probability of target attainment (PTA) obtained from 400 simulations for a target defined as 100% time > MIC (100% fT _{> MIC}): dotted blue: 20mg/kg every 8 hours as a 20-min infusion, dotted red: 40mg/kg every 8 hours as a 20-min infusion, dotted dark green: 20 mg/kg every 8 hours as a 3-hour infusion, blue: 60 mg/kg per day as a continuous infusion, red: 120 mg/kg per day as a continuous infusion.

Conclusion

Meropenem continuous infusion allows te reach the 100% fT _{> MIC} target in critically ill children with normal or increased renal clearance and those needed CRRT.

Background

Despite the improvement of surgical techniques and medical care, thrombotic complications still represent the primary cause of early graft failure and re-transplantation within the first 30 days following pediatric liver transplantation (PLT). Standardized approach for prevention is still lacking.

Objectives

Evaluating the effectiveness of early heparin prophylaxis infusion started 24 hours postoperatively at 10 UI/kg per hour on reducing venous thrombosis event (VTE) in the first 30 days after PLT.

Methods

Retrospective case-control study designed to compare the incidence of early VTE prior (2002-2010) and after (2011-2016) the introduction of the early heparin prophylaxis in our Institution.

Results

From 2002 to 2016, 479 pediatric patients received LT in our Centre with an overall one year survival of 0.9. 365 patients were eligible for the statistical analysis: 244 prior to heparin and 121 with heparin.

We report a lower incidence of VTE in the heparin group: 2,5% (3/121) versus 7,9% (19/244 patients) (p = 0.038).

27 variables considered potential risk factors for VTE were studied. After the multivariate analysis, heparin prophylaxis remained the unique factor significantly and independently associated to the early VTE with a HR = 0,22 (0,05 – 0,96), p 0,043.

In terms of 1 year overall survival, no significant differences between the 2 groups were shown, however we report 5 retransplantation prior to heparin versus 1 retransplantation with heparin.

Conclusion

Intravenous unfractionated heparin infusion started 24 hours postoperatively at 10 UI/kg per hour can be considered a valid and safe strategy to prevent VTE after PLT.

Background

Few data are available about patients receiving neuromuscular blocking agents (NMBAs) in pediatric intensive care units (PICU). Their use is often reported without clear and definite indications with conflicting data about the outcome of these patients.

Objectives

To describe the characteristics and outcome of children receiving prolonged NMBAs treatment in PICU.

Methods

Retrospective, multicenter study using a prospective electronic web-based-national-registry (Pediatric Intensive Care Unit Study Group Network-TIPNET) of patients admitted to 18 Italians’ PICUs (January 2010-October 2017). We included children (<18 years-of-age) receiving mechanical ventilation (MV) and compared patients who received NMBAs (Cur+) with children who did not receive them (Cur-).

Results

A total of 3848 patients were included, 504 (13%) Cur+. There were no significant differences about gender, comorbidities and PIM3 score between the two populations. Cur+ had a significantly lower age (20months [interquartile range (IQR) 5-65] vs 30months [IQR 8-83],p<0.001) and weight (10kg [IQR 5-18] vs 12kg [IQR 7-21]),p<0.001). They received MV more for respiratory (50%vs29%,p<0.001) and less for cardiac diseases (10%vs31%,p<0.001). Cur+ showed longer ventilation duration (6days [IQR 2-12] vs 3days [IQR 1-6],p<0.001) and a higher rate of use of high frequency oscillatory ventilation (18%vs3%,p<0.001). A logistic regression adjusted for age, gender and ventilation modality demonstrated a correlation between NMBAs use and mortality (p<0.001).

Conclusion

A non-negligible proportion of children in PICUs received NMBAs. Their use was more frequent in younger age, it is associated with prolonged use of MV and a higher mortality. Further studies are needed to clarify the specific indications, patients’ clinical features and the concomitant pharmacological management.

Background

Upper airway obstruction (UAO) is a severe complication occurring after endotracheal intubation in pediatric critically ill patients frequently causing extubation failure. Steroids have been proposed as treatment to prevent occurrence of UAO but there is no clear evidence of their effect in children.

Objectives

To determine if dexamethasone administration prior to extubation is effective to prevent postextubation respiratory difficulty secondary to UAO.

Methods

A multicenter double-blind randomized trial was carried out. Patients intubated longer than 48h were randomized to receive placebo or 4 doses of 0.25 mg/kg/6h dexamethasone starting 6-12 hours before extubation. Demographical, clinical and postextubation treatment variables were compared between groups.

Results

67 patients were included in the dexamethasone group and 70 in the placebo group. 27 patients were reintubated during follow up, 9 of them due to UAO. Basal characteristics of groups were comparable. Dexamethasone group had similar reintubation (22.9% vs 16.4%, p=0.344) and reintubation due to UAO rates (4.3% vs 9%, p=0.280) compared to Placebo. Occurrence of stridor in the first 48hrs after extubation was similar (34.3% vs 41.8%, p=0.366), and maximum Taussig score was also comparable (p=0.091) between groups. There was a trend towards a lower use of aerosolized epinephrine (21.4% vs 35.8%, p= 0.062) and budesonide (5.7% vs 14.9%, p=0.094) as rescue therapies in the dexamethasone group.

Conclusion

Our results do not provide enough evidence to recommend systematic administration of dexamethasone prior to extubation in critically ill children. Further research is needed to determine if it might decrease the need of rescue therapies.