"The proper study of mankind is man"--rather, men and women undergoing anesthesia and surgery.

“The Proper Study of Mankind Is Man”*—Rather, Men and Women Undergoing Anesthesia and Surgery STARTING in 1997, Hahn et al. introduced and developed the concept of volume kinetics, which describes the peak effects and clearance of intravenously infused fluids in terms similar to those used in pharmacokinetics to describe the peak effects and clearance of drugs. Stanski, in an editorial accompanying the landmark article by Svensen and Hahn in ANESTHESIOLOGY in 1997, commented that the volume kinetic approach could “allow for more rational design of intravenous fluid paradigms.” Toward that end, Hahn et al. have examined several key questions in volunteers and in experimental animals. One of the least expected observations, obtained in sheep, was that isoflurane anesthesia seemed to be associated with extravascular accumulation of infused crystalloid. However, in this issue of ANESTHESIOLOGY, Ewaldsson and Hahn convincingly demonstrate that, in humans, neither isoflurane nor propofol anesthesia is associated with extravascular fluid accumulation. The authors infer from their data that volume kinetics are powerfully influenced by hypotension, an inference that merits examination in the context of previous volume kinetic studies. In pharmacokinetics, an exogenous substance is introduced, blood or other fluids are repeatedly sampled, and the resulting temporal pattern is analyzed to determine important kinetic variables. In contrast, volume kinetics examines the clearance of endogenous substances, e.g., water, that already are present in considerable quantities. For such studies, an endogenous tracer is necessary, the best being the blood concentration of hemoglobin, which is an obligatory intravascular tracer. To confidently calculate volume kinetic variables, the blood concentration of hemoglobin should be repeatedly measured before, during, and after fluid infusion in a relative steady state. High-probability solutions to the kinetic equations necessitate that changes in potentially confounding physiologic and pharmacologic influences be minimized for a sufficient time interval to construct clearance curves. In practice, time intervals of 180 min after the beginning of an intravenous infusion have provided sufficient data for reliable kinetic analyses. Such time intervals of relative stability can be achieved easily in certain types of volunteer and animal studies. For example, in volunteers, isotonic crystalloid solutions were rapidly cleared, colloid solutions were less rapidly cleared, and crystalloid solutions produced higher peak volume expansion and more delayed clearance in hypovolemic than normovolemic volunteers. During intervals of relative stability in preeclamptic parturients, crystalloid solutions were more rapidly cleared than in normal volunteers. In experimental animals, isoflurane anesthesia was associated with similar clearance of infused crystalloids from blood but markedly delayed urinary excretion, implying greater extravascular retention. As in volunteers, hemorrhage in sheep both increased peak expansion and delayed clearance from blood. Pseudomonas bacteremia, which in sheep mimics many characteristics of clinical sepsis, unexpectedly did not influence volume kinetics. In sheep, continuous infusion of -adrenergic agonists dramatically accelerated, whereas agonists delayed, clearance of infused crystalloids. However, the clinical circumstances of anesthesia and surgery usually preclude 180 min of steady state conditions, the influences of surgical stress and surgically induced fluid shifts are difficult to separate from the influence of anesthesia, and blood loss confounds kinetic analyses based on measurements of the blood concentration of hemoglobin. Nevertheless, volume kinetic studies have been performed in patients undergoing surgery. During laparoscopic cholecystectomy in women undergoing sevoflurane–narcotic anesthesia, induction of anesthesia, before fluid infusion, was associated with 4.2% plasma dilution (equivalent to intravascular volume expansion); subsequent fluid infusion was associated with calculated kinetic variables that were similar to those acquired in female volunteers, despite marked inhibition by anesthesia of the infusion-associated diuresis seen in volunteers. In contrast, in men undergoing prostatectomy during enflurane anesthesia, crystalloid fluids seemed to produce greater volume expansion than in unanesthetized volunteers. In a heterogeneous group of patients undergoing elective surgery of variable magnitude during subarachnoid block or sevoflurane–narcotic general anesthesia, volume expansion was greater in patients undergoing general anesthesia, but urinary elimination was similarly reduced in both groups. Men undergoing short urologic procedures This Editorial View accompanies the following article: Ewaldsson C-A, Hahn RG: Kinetics and extravascular retention of acetated Ringer’s solution during isoflurane or propofol anesthesia for thyroid surgery. ANESTHESIOLOGY 2005; 103:460–9.