Does intranasal dexmedetomidine provide adequate plasma concentrations for sedation in children: a pharmacokinetic study.

BACKGROUND: Atomised intranasal dexmedetomidine administration is an attractive option when sedation is required for paediatric diagnostic procedures, as vascular access is not required. The risk of haemodynamic instability caused by dexmedetomidine necessitates better understanding of its pharmacokinetics in young children. To date, intranasal dexmedetomidine pharmacokinetics has only been studied in adults. METHODS: Eighteen paediatric patients received dexmedetomidine 1 or 2 µg kg-1 intranasally or 1 µg kg-1 i.v. Plasma concentrations were determined by liquid chromatography/mass spectrometry. Non-compartmental analysis provided estimates of Cmax and Tmax. Volume of distribution, clearance, and bioavailability were estimated by simultaneous population PK analysis of data after intranasal and i.v. administration. Dexmedetomidine plasma concentration-time profiles were evaluated by simulation for intranasal and i.v. administration. RESULTS: An average peak plasma concentration of 199 pg ml-1 was achieved 46 min after 1 µg kg-1 dosing and 355 pg ml-1 was achieved 47 min after 2 µg kg-1 dosing. A two-compartment pharmacokinetic model, with allometrically scaled parameters, adequately described the data. Typical bioavailability was 83.8% (95% confidence interval 69.5-98.1%). CONCLUSION: Mean arterial plasma concentrations of dexmedetomidine in infants and toddlers approached 100 pg ml-1, the low end reported for sedative efficacy, within 20 min of an atomised intranasal administration of 1 µg kg-1. Doubling the dose to 2 µg kg-1 reached this plasma concentration within 10 min and achieved almost twice the peak concentration. Peak plasma concentrations with both doses were reached within 47 min of intranasal administration, with an overall bioavailability of 84%.

Gastric emptying for liquids of different compositions in children.

BACKGROUND: Pre-operative fasting balances safety against patient discomfort. We compared the gastric emptying profiles of a novel clear, high protein drink against a "traditional" clear and a non-clear fluid. METHODS: We conducted a prospective cross-sectional study with 48 healthy volunteers, eight to 14 yr of age, fasted overnight and without risk factors for abnormal gastrointestinal motility. Subjects were randomized in equal ratio to ingest 296 ml of apple juice, 2% milk or Ensure Clear. The gastric antrum was seen by ultrasound in the right lateral decubitus position at baseline, after ingestion, then every 30 min thereafter until return to baseline or six h. Gastric antral cross-sectional area was measured independently by two anaesthetists, and compared between drinks. RESULTS: Gastric emptying differed between apple juice, 2% milk and Ensure Clear by analysis of co-variance (P<0.0001), and was faster in males than females (P<0.01). The terminal phase however was similar using interval-censored time to gastric emptying in a survival model (P=0.17) or by comparing proportions with empty stomach vs not empty at 90 min (P=1.0), 120 min (P=0.32), 150 min (P=0.11), 180 min (P=0.76) or 210 min (P=1.0). CONCLUSIONS: Despite early differences, clearance from the stomach of apple juice, 2% milk or Ensure Clear is similar at the terminal phase, which is the period of greatest relevance to preoperative fasting recommendations. The stomach is essentially clear by 3-3.5 h for all three drinks studied. The differentiation between liquids in current guidelines is not supported by this study. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT02938065 clinicaltrials.gov/ct2/show/NCT02938065.

Arginine-vasopressin therapy in hypotensive neonates and infants after cardiac surgery: response is unrelated to baseline ventricular function.

We hypothesised that infants with ventricular dysfunction after cardiac surgery have impaired haemodynamic response to arginine-vasopressin therapy. We retrospectively reviewed the medical records of neonates and infants treated with arginine-vasopressin within 48 hours of corrective or palliative cardiac surgery who underwent echocardiographic assessment of ventricular function before initiation of therapy. Patients were classified as "responders" if their systolic blood pressure increased by ⩾10% without increase in catecholamine score or if it was maintained with decreased catecholamine score. Response was assessed 1 hour after maximum upward titration of arginine-vasopressin. A total of 36 children (15 neonates) were reviewed (17 male). The median (interquartile) age was 10.4 weeks (1.1-26.9), and the median weight was 4.3 kg (3.2-5.8). Diagnoses included single ventricle (eight), arch abnormalities (five), atrioventricular septal defect (four), double-outlet right ventricle (three), tetralogy of Fallot (three), and others (13). In all, 12 patients (33%) had ventricular dysfunction. Only 15 (42%) responded favourably according to our definition 1 hour after the "target" arginine-vasopressin dose was achieved. Ventricular dysfunction was not associated with poor response. The overall mortality was 25%, but mortality in patients with ventricular dysfunction was 42%. Favourable response was associated with shorter ICU stay (9.5 days versus 19.5 days, p=0.01). We conclude that arginine-vasopressin fails to increase blood pressure in ~50% of hypotensive children after cardiac surgery. The response rate does not increase with duration of therapy. Ventricular function does not predict haemodynamic response. The mortality in this group is very high. Prospective comparison of vasopressin with other vasoactive agents and/or inotropes is warranted.

Posterior reversible encephalopathy syndrome: a report of a case with atypical features.

We report a case of a young woman presenting with profound depression of consciousness and intra-uterine death in the late stages of an unbooked pregnancy. She proceeded to develop features of cardiovascular, renal, hepatic and haematological failures. The patient was challenging to manage in view of uncertainty regarding the underlying cause, and required multidisciplinary consultation. A diagnosis was subsequently made of posterior reversible encephalopathy syndrome in the context of pre-eclampsia. We review the typical presentation and wide-ranging associations of this recently described clinico-neuroradiological syndrome, and look at how appropriate management may lead to rapid resolution of its often life-threatening features. We highlight the importance to anaesthetists and critical care physicians of recognising even atypical cases such as this one in view of key differences in management from similarly presenting conditions.