The pharmacokinetics of dexmedetomidine in children are predictable with a terminal half-life of 1.8 h. Hemodynamic responses decreased with increasing doses of dexmedetomidine. Respiratory responses were maintained, whereas sedation was transient.
Various hydroxyethyl starch (HES) preparations have been used for decades to augment blood volume. There has been concern recently regarding possible adverse outcomes when using HES in the intensive care setting, especially in patients with septic shock. However, the pharmacokinetic and pharmacodynamic properties of HES preparations depend on their chemical composition and source material. Thus, different clinical conditions could result in differing effectiveness and safety for these preparations. Consequently, we assessed the safety of tetrastarches when used during surgery, using a formal search, that yielded 59 primary full publications of studies that met a priori inclusion criteria and randomly allocated 4529 patients with 2139 patients treated with tetrastarch compared with 2390 patients treated with a comparator. There were no indications that the use of tetrastarches during surgery induces adverse renal effects as assessed by change or absolute concentrations of serum creatinine or need for renal replacement therapy (39 trials, 3389 patients), increased blood loss (38 trials, 3280 patients), allogeneic erythrocyte transfusion (20 trials, 2151 patients; odds ratio for HES transfusion 0.73 [95% confidence interval = 0.61-0.87], P = 0.0005), or increased mortality (odds ratio for HES mortality = 0.51 [0.24-1.05], P = 0.079).
With the development of a new generation of hydroxyethyl starches (HES), there has been renewed interest in their clinical potential. High doses of first- and second-generation HES were associated with adverse effects on renal function, coagulation, and tissue storage, thereby limiting their clinical applicability. Newer HES products have lower molar substitution and in vivo molecular weight, resulting in more rapid metabolism and clearance. In this review article, the differences between HES generations are highlighted, with particular emphasis on the improved safety profile of the third generation products. These improvements have been achieved with no loss of efficacy, and they contradict the assumption that efficacy of HES solutions is directly linked to plasma concentration. The impact of source material on structure and pharmacokinetics is highlighted, and the role of the carrier solution is critically assessed.
It has been suggested that haemodilution with saline may increase whole blood coagulation. This study was conducted in two parts. First, we investigated the effect of in vitro dilution of blood with saline on whole blood coagulation as measured by the thrombelastogram (TEG). Blood (4 ml) was diluted with 0.9% saline 1 ml and coagulation compared with that of an undiluted control specimen obtained concurrently from the same subject. In the second part, the study was repeated using a modified gelatin colloidal solution (Haemaccel) as the diluent. The r time, k time and r + k time were decreased relative to control in both diluent groups. The alpha angles were increased compared with control in both groups while maximum amplitude was unchanged in the Haemaccel diluted group. We conclude that haemodilution per se increases the coagulability of whole blood in vitro, but that saline haemodilution has a more marked effect on final clot strength.
Seventeen anaesthetics are described in 16 patients with phaeochromocytoma in whom magnesium sulphate (MgSO4) was the principal anti-adrenergic agent used. In 15 of the 17 anaesthetics, MgSO4 produced satisfactory control of cardiovascular changes at induction and tracheal intubation, but in four of these additional sodium nitroprusside was required to control the arterial pressure during handling of the tumour. In one pregnant patient undergoing Caesarean section, MgSO4 was ineffective in controlling cardiovascular disturbances because of inadequate serum magnesium concentrations. This patient had a magnesium deficit before operation. In another patient, diagnosis was made during operation and MgSO4 provided satisfactory control of the crisis. Catecholamine release was studied in five patients and MgSO4 was found to reduce catecholamine concentrations from the time of induction until tumour handling.
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