Individualized dosing with anesthetic agents.

The development of fundamental pharmacokinetics and pharmacodynamics concepts has enabled anesthesiologists to choose and dose anesthetic agents on a rational basis. The application of these concepts to a variety of clinical scenarios and patient populations makes it possible to individualize the dose, thereby decreasing the risk of complications. As more knowledge is gained about the sometimes profound differences in drug response, empirical dosing such as in milligrams per kilogram of total body weight is disappearing from the anesthesia specialty.

Dose adjustment of anaesthetics in the morbidly obese.

Anaesthesiologists must be prepared to deal with pharmacokinetic and pharmacodynamic (PD) differences in morbidly obese individuals. As drug administration based on total body weight can result in overdose, weight-based dosing scalars must be considered. Conversely, administration of drugs based on ideal body weight can result in a sub-therapeutic dose. Changes in cardiac output and alterations in body composition affect the distribution of numerous anaesthetic drugs. With the exception of neuromuscular antagonists, lean body weight is the optimal dosing scalar for most drugs used in anaesthesia including opioids and anaesthetic induction agents. The increased incidence of obstructive sleep apnoea and fat deposition in the pharynx and chest wall places the morbidly obese at increased risk for adverse respiratory events secondary to anaesthetic agents, thus altering the PD properties of these drugs. Awareness of the pharmacology of the commonly used anaesthetic agents including induction agents, opioids, inhalation agents and neuromuscular blockers is necessary for safe and effective care of morbidly obese patients.

The history of anesthesia for thoracic surgery.

Today, thoracic surgeons routinely perform complex operations on even the most complicated patient. However, just 75 years ago the ability to operate within the chest was strictly limited to only the simplest and quickest procedures. The dramatic advances in the specialty of thoracic surgery have closely paralleled the introduction of new anesthetic practices, equipment and drugs. This review will identify major events in the history of anesthesia for thoracic surgery.

The haemodilution enhanced onset of coagulation as measured by the thrombelastogram is transient.

BACKGROUND AND OBJECTIVE: Crystalloid haemodilution has been widely found to enhance coagulation onset, but the duration of this effect has never been documented. METHODS: Twelve healthy, consenting volunteers had a rapid infusion of 14 mL kg-1 of normal (0.9%) saline. Blood samples were taken, prior to (control), and immediately after (30 min) the rapid saline infusion was completed (30 min). They were then repeated at regular intervals up to 120 min. Haematocrit/platelet counts were taken to determine the degree of dilution and thrombelastograms, with and without platelet antagonists (ReoPro, Abciximab), were measured in all samples. Antithrombin levels were selectively measured. RESULTS: The haematocrit and platelet count showed a rapid dilutional decrease at 30 min (mean of -12.2% and -14.4%, respectively), with values returning towards baseline within 15 min after finishing the infusion. There was a significantly faster onset of coagulation (decrease in r-time) in the post-infusion sample (30 min) compared to control (P<0.05), again returning towards normal as the dilution effect was reversed. Similar thrombelastograms findings were evident in the plasma factor only group (platelets inhibited by ReoPro). Antithrombin levels changed in keeping with the haemodilution effect (P<0.0001). There was a linear relationship between antithrombin and thrombelastograms r-time (P=0.012). CONCLUSION: The faster onset of coagulation brought on by haemodilution return towards normal as the dilutional effect is reversed. This effect is mediated through plasma clotting factors. Of interest is the significant inverse correlation of the onset of coagulation increasing as the antithrombin levels decreased with dilution.

Large volume N2O uptake alone does not explain the second gas effect of N2O on sevoflurane during constant inspired ventilation.

BACKGROUND: The second gas effect (SGE) is considered to be significant only during periods of large volume N(2)O uptake (VN(2)O); however, the SGE of small VN(2)O has not been studied. We hypothesized that the SGE of N(2)O on sevoflurane would become less pronounced when sevoflurane administration is started 60 min after the start of N(2)O administration when VN(2)O has decreased to approximately 125 ml min(-1), and that the kinetics of sevoflurane under these circumstances would become indistinguishable from those when sevoflurane is administered in O(2). METHODS: Seventy-two physical status ASA I-II patients were randomly assigned to one of six groups (n=12 each). In the first four groups, sevoflurane (1.8% vaporizer setting) administration was started 0, 2, 5 and 60 min after starting 2 litre min(-1) O(2) and 4 litre min(-1) N(2)O, respectively. In the last two groups, sevoflurane (1.8 or 3.6% vaporizer setting) was administered in 6 litre min(-1) O(2). The ratios of the alveolar fraction of sevoflurane (Fa) over the inspired fraction (Fi), or Fa/Fi, were compared between the groups. RESULTS: Sevoflurane Fa/Fi was larger in the N(2)O groups than in the O(2) groups, and it was identical in all four N(2)O groups. CONCLUSIONS: We confirmed the existence of a SGE of N(2)O. Surprisingly, when using an Fa of 65% N(2)O, the magnitude of the SGE was the same with large or small VN(2)O. The classical model and the graphical representation of the SGE alone should not be used to explain the magnitude of the SGE. We speculate that changes in ventilation/perfusion inhomogeneity in the lungs during general anaesthesia result in a SGE at levels of VN(2)O previously considered by most to be too small to exert a SGE.

Stroke volume equation for impedance cardiography.

The study's goal was to determine if cardiac output (CO), obtained by impedance cardiography (ICG), would be improved by a new equation N, implementing a square root transformation for dZ/dtmax/Z0, and a variable magnitude, mass-based volume conductor Vc. Pulmonary artery catheterisation was performed on 106 cardiac surgery patients pre-operatively. Post-operatively, thermodilution cardiac output (TDCO) was simultaneously compared with ICG CO. dZ/dtmax/Z0 and Z0 were obtained from a proprietary bioimpedance device. The impedance variables, in addition to left ventricular ejection time TLVE and patient height and weight, were input using four stroke volume (SV) equations: Kubicek (K), Sramek (S), Sramek-Bernstein (SB), and a new equation N. CO was calculated as SV x heart rate. Data are presented as mean +/- SD. One way repeated measures of ANOVA followed by the Tukey test were used for inter-group comparisons. Bland-Altman methods were used to assess bias, precision and limits of agreement. P< 0.05 was considered statistically significant. CO implementing N (6.06 +/- 1.48 l min(-1)) was not different from TDCO (5.97 +/- 1.41 l min(-1)). By contrast, CO calculated using K (3.70 +/- 1.53 l min(-1)), S (4.16 +/- 1.83 l min(-1)) and SB (4.37 +/- 1.82 l min(-1)) was significantly less than TDCO. Bland-Altman analysis showed poor agreement between TDCO and K, S and SB, but not between TDCO and N. Compared with TDCO, equation N, using a square-root transformation for dZ/dtmax/Z0, and a mass-based Vc, was superior to existing transthoracic impedance techniques for SV and CO determination.

Nitrous oxide and laparoscopic bariatric surgery.

BACKGROUND: Nitrous oxide (N2O) is frequently used to supplement more potent anesthetic agents. One side-effect of N2O is its ability to expand an air-containing space. We investigated if N2O adversely affected operating conditions by distending normal bowel during laparoscopic bariatric procedures. METHODS: 50 morbidly obese patients were divided into 2 study groups. Group 1 patients were ventilated with a halogenated anesthetic/oxygen/air mixture, while Group 2 received a halogenated anesthetic/oxygen/N2O mixture. At 30, 60, and 90 min intervals during the operation, the surgeon was asked if N2O was being used. RESULTS: The surgeons responded correctly only 42% (30 min), 50% (60 min), and 48% (90 min) of the time. In Group 2 (N2O) patients, they incorrectly answered that N2O was not being used 88% (30 min), 68% (60 min), and 68% (90 min); and in Group 1 (air) patients, they incorrectly answered that N2O was being used 28% (30 min), 32% (60 min), and 36% (90 min) of the time. CONCLUSION: We found that using N2O did not cause noticeable bowel distention during laparoscopic bariatric procedures of relatively short duration.