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Pharmacokinetics and tolerability of a new hydroxyethyl starch (HES) specification [HES (130/0.4)] after single-dose infusion of 6% or 10% solutions in healthy volunteers. Hydroxyethyl starch in balanced electrolyte solution (Hextend((R)))-pharmacokinetic and pharmacodynamic profiles in healthy volunteers. Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients. Oliguria as predictive biomarker of acute kidney injury in critically ill patients. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury a multicenter pooled analysis of prospective studies. Nephrology consultation in acute renal failure: Does timing matter? Early nephrologist involvement in hospital-acquired acute kidney injury: a pilot study. Was it the nephrologists or the fluid? Clinical review: volume of fluid resuscitation and the incidence of acute kidney injury - a systematic review. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Reduced production of creatinine limits its use as marker of kidney injury in sepsis. Distribution of normal saline and 5% albumin infusions in septic patients. Assessment of intravascular volume by transthoracic echocardiography during therapeutic hypothermia and rewarming in cardiac arrest survivors. Capillary leakage in post-cardiac arrest survivors during therapeutic hypothermia - a prospective, randomised study. Use of serum creatinine concentrations to determine renal-function.

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Critical Care

ISSN: 1364-8535

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Succinylcholine, a neuromuscular blocking agent commonly used in surgical procedures to aid in endotracheal intubation, acts as a depolarizing neuromuscular blocker by mimicking the action of acetylcholine, thus generating an action potential at the motor end-plate. Succinylcholine has a half-life of 0.7 min and a volume of distribution of 0.02–0.04 L/kg. The action of succinylcholine is terminated by its diffusion away from the motor end-plate into the blood, where it is hydrolyzed by BChE ( 3 ). Normally, muscle function is restored approximately 10 min after discontinuation of the drug. Extended blockade with succinylcholine occurs in a subset of individuals who have BChE variants that either lack sufficient quantity of the enzyme or demonstrate a decreased affinity for substrate, thereby causing prolonged paralysis.

BChE is the product of the BCHE (butyrylcholinesterase) gene on chromosome 3 region 3q26. The gene consists of 73 kilobases in 4 exons separated by 3 introns ( 3 ). Mutations in the BCHE gene encode BChE protein products with varying reductions in activity that produce extended blockade and apnea in patients after exposure to succinylcholine. These genetically determined enzyme variants are characterized by decreased BChE production (quantitative variants) or by the production of dysfunctional BChE molecules having decreased to no activity (qualitative variants) ( Hey DudeWally Linen 2dgcm0NniF
). BChE deficiency is often recognized only after an individual experiences unexpected periods of prolonged paralysis after succinylcholine administration.

A biochemical test from the 1950s for the phenotypic identification of BChE variants helped determine that the pharmacogenetic effect of BChE variants was familial ( La CanadienneStefania 2H4qU
, Kenneth Cole Reaction Tole Booth Suede Platform Slingback 88Avl4DbM
, 6 ). The test quantifies BChE enzyme activity in the serum in the presence and absence of the competitive inhibitor dibucaine, allowing the calculation of a “dibucaine number” (DN) that corresponds to the percentage of enzymatic inhibition: DN = [1 − (Inhibited BChE activity)/(Total BChE activity)] × 100, where BChE activity is in units per liter. Together, the BChE activity and the DN can be used to determine an individual's biochemical phenotype ( Lugz Strife Denim RvipqEA

View this table:
Table 1. Characteristics associated with BChE phenotypes.

With a prevalence of 96%, the most common phenotype is the usual (U) phenotype, which is characterized by a DN >80%. Individuals with this phenotype respond normally to succinylcholine administration with neuromuscular junction recovery achieved in approximately 10 min after exposure. In contrast, individuals with the atypical (A) phenotype have a DN <32% and experience prolonged paralysis after exposure to succinylcholine. A single allele at a frequency of 1 in 3000 is known to produce the A phenotype ( 4 ). Approximately 3% of individuals have the heterozygous UA phenotype and demonstrate clinical and biochemical properties between the U and A phenotypes. The fluoride-resistant (F) phenotype shows increased resistance to inhibition by fluoride and reduces an individual's ability to hydrolyze succinylcholine. There are 2 known fluoride-resistant mutations, but their frequency is very rare (1 in 150 000 individuals) ( Sigerson Morrison Kairos 2 Ml34rMPcXn
). Individuals with the rare silent (S) phenotype completely lack or have only minimal BChE activity ( Pleaser Delight 20193 OpenToe Fringe Boot Womens vCf326Se

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