Mazhong Zhang

Pharmacokinetics of dexmedetomidine in Chinese post‐surgical intensive care unit patients

Background: Dexmedetomidine is a rather new drug in China. We sought to describe the pharmacokinetics of dexmedetomidine in patients requiring post‐operative sedation and ventilation in our surgical intensive care unit.

The sedative effects and the attenuation of cardiovascular and arousal responses during anesthesia induction and intubation in pediatric patients: a randomized comparison between two different doses of preoperative intranasal dexmedetomidine

Premedication with intranasal dexmedetomidine (DEX) has shown to be an effective sedative in pediatric patients. This prospective, randomized, and controlled investigation was designed to evaluate whether the difference in intranasal DEX dosing would produce different beneficial effects on the attenuation of cardiovascular and arousal responses during anesthesia induction and intubation.

Population pharmacokinetics of intravenous bolus etomidate in children over 6 months of age.

Background:  Information has been very limited on the population pharmacokinetics (PK) of etomidate in pediatric patients. The purpose of this study was to characterize the PK of etomidate in children.

Noninvasive cardiac output monitoring using bioreactance‐based technique in pediatric patients with or without ventricular septal defect during anesthesia: in comparison with echocardiography

We evaluated the use of bioreactance‐based noninvasive cardiac output (CO) monitoring technique (NICOM™, CONICOM) in pediatric patients with or without ventricular septal defect (VSD) during anesthesia induction to determine its agreement with the measurements assessed by echocardiography (echo, COECHO).

Comparison of Adrenal Suppression between Etomidate and Dexmedetomidine in Children with Congenital Heart Disease

Background The aim of this study was to compare plasma cortisol concentration during anesthesia of children with congenital heart disease who received dexmedetomidine (DEX) with those who received etomidate (ETO). Material/Methods We recruited 99 ASA physical status II–III pediatric patients scheduled for congenital heart disease (CHD) corrective surgery and divided into them into 3 groups. Group DEX received an infusion of DEX intravenously with a bolus dose of 0.5 μg·kg−1 within 10 min during anesthesia induction, followed by a maintenance dose of DEX 0.5 μg·kg−1·h−1. Group ETO received ETO intravenously with a bolus dose of 0.3 mg·kg−1 without a maintenance dose. Group CON received routine anesthetics as controls. The preset timepoints were: before anesthesia induction (T0), at the end of induction (T1), 30 min after anesthesia induction (T2), at the time of aortic and inferior vena catheterization (T3), and at 180 min (T4) and 24 h (T5) after anesthesia induction. Results The cortisol concentration decreased gradually after anesthesia induction in all groups, and returned to baseline values after 24 h. The cortisol concentration was significantly lower in Group ETO children than in Group DEX or group CON at T4. Conclusions The plasma concentrations of cortisol decreased in CHD children after the operation, but returned to baseline after 24 h of anesthesia induction. The adrenal cortex function inhibition induced by ETO in CHD children is longer and more serious than that induced by DEX (if any) during the preoperative period.

The agreement between oscillometric and intra-arterial technique for blood pressure monitoring in the lower extremities for infants and toddlers undergoing aortic coarctation repair.

Anesthetic management for patients undergoing surgical repair of aortic coarctation (CoA) should include constant blood pressure monitoring of the right upper extremity and a lower extremity. The delayed or absent pulse in the lower limbs often leads to unsuccessful arterial cannulation in infants and the oscillometric technique used for blood pressure measurement. The aim of this study was to evaluate the agreement between the oscillometric method and intra‐arterial technique for blood pressure monitoring in the lower limbs of infants undergoing CoA.

Pediatric preoperative risk factors to predict postoperative ICU admission and death from a multicenter retrospective study.

Although some studies have investigated the potential predictors of perioperative mortality, there are few specifically for pediatrics.

Serum Antibodies to the Heparin/Platelet Factor 4 Complex Are an Independent Predictor of Thrombotic Complications Following Pediatric Fontan Surgery

Antibodies to the heparin/platelet factor 4 complex (heparin/PF4) are linked to the pathogenesis of heparin-induced thrombocytopenia (HIT) and to the thrombotic complications. We investigated thrombotic events during early follow-up in a pediatric cardiac surgical population to ascertain whether there is a relation between heparin/PF4 antibody concentration and post-surgical thrombotic complications. One hundred and five consecutive pediatric patients treated by Fontan surgery were studied. The presence of serum heparin/PF4 immunoglobulins IgG, IgA, and IgM (collectively termed HIT antibodies) were measured in preoperative and postoperative blood samples by enzyme-linked immunosorbent assay. On day six after Fontan surgery, HIT-related thromboses was identified in total of 11 patients (10.5%). HIT antibodies were detected in 34 of 105 patients (32.4%). The post-surgical nadir platelet count was significantly lower in patients who developed antibodies (p < 0.001). We found the odds ratio (OR) for this composite endpoint was 4.06 (p < 0.001). Seropositive status for heparin/PF4 antibodies was an independent predictor of thrombotic events (OR 2.28; p < 0.001). Quintile analysis revealed that the median nadir platelet value was significantly lower in patients with higher HIT antibody titers. Patients in the highest quintile of HIT antibody titer all experienced thrombotic events, while only two thrombotic events occurred in patients in the lowest quintile (p < 0.001). Heparin-induced thrombocytopenia is a rare occurrence in pediatric cardiac surgical patients. Patients who develop antibodies to the heparin/PF4 complex have a significantly higher rate of postoperative thrombotic events than patients who lack these antibodies. Within the seropositive group, the risk of developing thrombosis increased with the plasma antibody concentration.

Cyclic stretch induced IL-33 production through HMGB1/TLR-4 signaling pathway in murine respiratory epithelial cells

Interleukin 33 (IL-33), an inflammatory and mechanically responsive cytokine, is an important component of a TLR4-dependent innate immune process in mucosal epithelium. Although TLR4 also plays a role in sensing biomechanical stretch, a pathway of stretch-induced TLR4-dependent IL-33 biosynthesis has not been revealed. In the current study, we show that short term (6 h) cyclic stretch (CS) of cultured murine respiratory epithelial cells (MLE-12) increased intracellular IL-33 expression in a TLR4 dependent fashion. There was no detectable IL-33 in conditioned media in this interval. CS, however, increased release of the notable alarmin, HMGB1, and a neutralizing antibody (2G7) to HMGB1 completely abolished the CS mediated increase in IL-33. rHMGB1 increased IL-33 synthesis and this was partially abrogated by silencing TLR4 suggesting additional receptors for HMGB1 are involved in its regulation of IL-33. Collectively, these data reveal a HMGB1/TLR4/IL-33 pathway in the response of respiratory epithelium to mechanical stretch.

Unrepaired Tetralogy of Fallot-related Pathophysiologic Changes Reduce Systemic Clearance of Etomidate in Children.

BACKGROUND: Pathophysiologic changes in children with congenital heart disease may alter the effect of drugs by influencing the pharmacokinetics (PK). Considering the limited literature that describes the PK of etomidate in pediatric patients, especially in those with tetralogy of Fallot (TOF), our aim was to characterize the PK of etomidate and explore the effects of TOF. METHODS: Twenty-nine pediatric patients (15 with TOF and 14 with normal cardiac anatomy) scheduled to undergo elective surgery under general anesthesia were recruited in the study. All children received etomidate 60 &mgr;g/kg/min intravenously until a bispectral index of ⩽50 was reached for 5 seconds during anesthesia induction. Arterial blood samples were drawn and analyzed. Population analysis was performed by using NONMEM to define PK characteristics. The estimates were standardized to a 70-kg adult using a per-kilogram model. RESULTS: Data consisting of 244 samples from 29 children with a mean age of 236 days (range, 86–360 days) were used, including a TOF group with a mean age of 250 days (range, 165–360 days) and a normal cardiac anatomy group with a mean age of 221 days (range, 86–360 days). A 3-compartment disposition model was best fitted to describe the PK of etomidate. The introduction of TOF as a covariate for systemic clearance (Cl1) improved the model and resulted in a significant reduction of objective function (&Dgr;objective function = −7.33; P = .0068), which means that TOF was a significant covariate of Cl1, and the etomidate Cl1 in children with TOF (1.67 × (weight [WT]/70 kg) L/min) was lower than those with normal cardiac anatomy (2.28 × (WT/70 kg) L/min). Other PK parameter values were as follows: V1 = 8.05 × (WT/70 kg) L; V2 = 13.7 × (WT/70 kg) L; V3 = 41.3 × (WT/70 kg) L; Cl2 = 3.35 × (WT/70 kg) L/min; Cl3 = 0.563 × (WT/70 kg) L/min. CONCLUSIONS: A decreased systemic clearance for etomidate in children with TOF resulted in a lower required infusion rate and variation with time to achieve the same plasma concentration and maintain an equivalent target concentration or have longer sedation and recovery times after bolus or continuous infusion than normal children.