Sufentanil pharmacokinetics in a full-term neonate treated with extracorporeal membrane oxygenation: a case report.

INTRODUCTION: Sufentanil is a potent analgesic drug used for pain management. A few studies describe the pharmacokinetics of sufentanil in neonates; however, no pharmacokinetic data about sufentanil during extracorporeal membrane oxygenation have been published yet. CASE REPORT: A 1-day-old neonate with moderate hypoxic-ischemic encephalopathy received veno-arterial extracorporeal membrane oxygenation support for refractory respiratory and circulatory failure. Sufentanil plasma concentrations were determined during both extracorporeal membrane oxygenation (n = 14) and non-extracorporeal membrane oxygenation (n = 17) period. Based on these measurements, individual sufentanil pharmacokinetic parameters were calculated. DISCUSSION: We observed increased sufentanil volume of distribution (11.6 vs 5.6 L/kg) and decreased sufentanil clearance (0.535 vs 0.746 L/h/kg) in extracorporeal membrane oxygenation period. The increment of volume of distribution was attributed to ECMO influence, while difference in clearance was probably due to drug interaction. CONCLUSIONS: This is the first description of sufentanil pharmacokinetics in neonate treated with extracorporeal membrane oxygenation. We observed considerably larger volume of distribution during extracorporeal membrane oxygenation period in comparison with non-extracorporeal membrane oxygenation period.

Severity of asphyxia is a covariate of phenobarbital clearance in newborns undergoing hypothermia.

AIM: Phenobarbital (PB) pharmacokinetics (PK) in asphyxiated newborns show large variability, not only explained by hypothermia (HT). We evaluated potential relevant covariates of PK of PB in newborns treated with or without HT for hypoxic-ischemic encephalopathy (HIE). METHODS: Clearance (CL), distribution volume (Vd) and elimination half-life (t1/2) were calculated using one-compartment analysis. Covariates were clinical characteristics (weight, gestational age, hepatic, renal, and circulatory status), comedication and HIE severity [time to reach normal aEEG pattern (TnormaEEG), dichotomous, within 24 h] and asphyxia severity [severe aspyhxia = pH ≤7.1 + Apgar score ≤5 (5 min), dichotomous]. Student's t-test, two-way ANOVA, correlation and Pearson's chi-square test were used. RESULTS: Forty newborns were included [14 non-HT; 26 HT with TnormaEEG <24 h in 14/26 (group1-HT) and TnormaEEG ≥24 h in 12/26 (group2-HT)]. Severe asphyxia was present in 26/40 [5/14 non-HT, 11/14 and 10/12 in both HT groups]. PB-CL, Vd and t1/2 were similar between the non-HT and HT group. However, within the HT group, PB-CL was significantly different between group1-HT and group2-HT (p = .043). ANOVA showed that HT (p = .034) and severity of asphyxia (p = .038) reduced PB-CL (-50%). CONCLUSION: The interaction of severity of asphyxia and HT is associated with a clinical relevant reduced PB-CL, suggesting the potential relevance of disease characteristics beyond HT itself.

Pre- and Post-Race Hydration Status in Hyponatremic and Non-Hyponatremic Ultra-Endurance Athletes.

The monitoring of body mass (BM), plasma sodium concentration ([Na⁺]) and urinary specific gravity (Usg) are commonly used to help detect and prevent over- or dehydration in endurance athletes. We investigated pre-and post-race hydration status in 113 amateur 24-h ultra-runners, 100-km ultra-runners, multi-stage mountain bikers and 24-h mountain bikers, which drank ad libitum without any intervention and compared results of hyponatremic and non-hyponatremic finishers. On average, pre-race plasma [Na⁺] and both pre- and post-race levels of Usg and BM were not significantly different between both groups. However, nearly 86% of the post-race hyponatremic (exercise-associated hyponatremia, EAH) and 68% of the normonatremic (non-EAH) ultra-athletes probably drank prior the race greater volumes than their thirst dictated regarding to individual pre-race Usg levels. Fluid intake during the race was equal and was not related to plasma [Na⁺], Usg or BM changes. A significant decrease in post-race plasma [Na⁺], BM and an increasement in post-race Usg was observed in EAH and non-EAH finishers. Moreover, pre-race plasma [Na⁺] was inversely associated with post-race percentage change in plasma [Na⁺], and pre-race Usg and urinary [Na⁺] with percentage change in Usg in both groups with and without post-race EAH. Thirteen (11.5%) finishers developed post-race EAH (plasma [Na⁺] < 135 mM). The incidence of EAH in ultra-endurance athletes competing in the Czech Republic was higher than reported previously.

Number of severe bleeding complications according to classification used: Is unified classification of bleeding complications really necessary?

BACKGROUND: To compare the number of severe periprocedural bleeding complications from the total number of bleeding complications associated with diagnostic selective coronary angiography or percutaneous coronary intervention (PCI) when using different classifications (TIMI, GUSTO, PLATO, BARC) and to relate these classifications to real hemodynamic status of evaluated patients. METHODS: We analyzed data from 106 patients who underwent invasive procedure for ischemic heart disease (selective coronary angiography/PCI) and suffered from any type of bleeding complication. RESULTS: The number of bleeding according to impacts on hemodynamic status and consequent treatment shows that 54.7% of all bleedings did not need any specific therapy. Bleeding leading to death, hemorrhagic shock, hemodynamic instability, administration of blood transfusion, surgical procedure and local treatment occurred in 6.6%, 1.9%, 5.7%, 14.2%, 2.8%, and 14.2%, respectively. The results comparing bleeding classifications demonstrate that the rate of severe bleeding complications may increase up to 4 times when different classifications are used on the same group of patients (TIMI 9.4%, GUSTO 15.1%, PLATO 39.2% and BARC 35.9%). The power of association between severe bleeding determined by these classifications and real hemodynamic compromise using Kendall's tau-c correlation is -0.4106 (95% CI -0.599 to -0.222), -0.5355 (95% CI -0.718 to -0.353), -0.5513 (95% CI -0.729 to -0.374) and -0.7552 (95% CI -0.897 to -0.612) for TIMI, GUSTO, PLATO and BARC, respectively. CONCLUSIONS: The data show significant dependence of percentage of severe periprocedural bleeding complications on selected classification. The strongest association between severe bleeding and real hemodynamic status was found for BARC classification as this classification seems to be promising for future general use.