Jerry M. Calkins

Thiopental disposition in lean and obese patients undergoing surgery.

The effect of obesity on the disposition kinetics of thiopental was studied in seven morbidly obese (age 25 to 46 years) and eight age-matched lean patients (age 25 to 43 years), undergoing primarily abdominal surgery. Based upon total (bound + free) thiopental concentrations, the average (±SD) volumes of distribution in the terminal disposition phase and at steady-state (Vβ and Vss) were significantly larger in the obese (7.94 ± 4.55 1/kg and 4.72 ± 2.73 1/kg, respectively) than in the age-matched lean patients (1.95 ± 0.63 1/kg and 1.40 ± 0.46 1/kg, respectively). Clearance of total thiopental, normalized for total body weight was not significantly different between the obese (0.18 ± 0.081 · h−1 · kg−1) and lean patients (0.2 ± 0.06 1 · h−1 · kg−1). However, total body clearance not normalized for total body weight was significantly larger in the obese (24.98 ± 14.87 1/h) than in the lean patients (11.86 ± 3.66 1/h). The elimination half-life of thiopental was significantly longer in the obese (27.85 h) than in the lean patients (6.33 h) and (his difference was primarily a function of the larger apparent volume of distribution for thiopental. The unbound fraction of thiopental in serum (range, 17.8 per cent to 27.6 per cent) was not correlated with the degree of obesity. The most appropriate means of comparing intrinsic metabolizing capacity (i.e., normalized vs. non-normalized for weight) between lean and obese subjects remains unresolved.

Cardiac output measurements. A review of current techniques and research

Cardiac output is the volume of blood ejected by the heart per unit time. It is a useful measurement in that it can be used to evaluate overall cardiac status in both critically ill patients and patients with suspected cardiovascular disease. An ideal cardiac output measurement system would have automated continuous output capability, be minimally invasive, accurate, fast, small, low cost and clinically adaptable. This paper presents a theoretical and practical description of the variety of clinical techniques in use today and lists their advantages and shortcomings with respect to the ideal system. Included are the Fick method, indicator dilution techniques, velocity measurements and transthoracic impedance and combined Doppler ultrasound as noninvasive techniques. In addition, several experimental methods are described along with their desirable features and possible constraints. These include intravascular heating/recording, thermistor tracking of cardiac output, ejection fraction measurements and magnetic susceptability plethysmography.

Thiopental Disposition as a Function of Age in Female Patients Undergoing Surgery

The effect of age on the disposition kinetics of thiopental was studied in 22 lean female patients having a body mass index (weight (kg/height(m)2) less than 30 and whose age ranged between 25 to 83 years. Patients underwent primarily abdominal surgery. A strong positive correlation between age and the apparent volumes of distribution, V beta and Vss, was found (P less than 0.001). No significant relationship was found between total body clearance and age. The elimination half-life (t1/2) of thiopental increased with age, and was primarily a function of volume of distribution. The free or unbound fraction of thiopental in serum (alpha) ranged between 0.168 and 0.276 and was significantly correlated with age (P less than 0.005). Multiple regression analysis indicated that age was the independent variable which contributed most the variability in t1/2, V beta, and Vss. No conclusion can be reached concerning the potential differences in anesthetic induction doses required as a function of age; however, these data suggest that care may be required in the use of a balanced anesthetic technique in the elderly as a result of prolonged elimination.

Hemodynamic effects of high-frequency jet ventilation

The hemodynamic effects of high-frequency jet ventilation (HFJV) and conventional ventilation were compared in normovolemic and functionally hypovolemic dogs. In normovolemic animals, no differences in hemodynamic function were found among spontaneous ventilation, conventional ventilation, and HFJV. When venous return was impaired by 15 cm H2O PEEP, cardiac index and stroke index were 25% higher with HFJV than with conventional ventilation (P < 0.05). In another study with PEEP, conventional ventilation was compared to spontaneous ventilation, HFJV synchronized to five different parts of the cardiac cycle, and asynchronous HFJV. Heart rate was 15% lower and mean arterial pressure was 26% lower with conventional ventilation than with HFJV modes (P < 0.05). There were no differences between synchronous and asynchronous HFJV. These results indicate that hemodynamic dysfunction may be less likely with HFJV than conventional ventilation. No advantage of synchronizing jet pulsations to a specific part of the cardiac cycle could be demonstrated.

Effects of dilution, pressure, and apparatus on hemolysis and flow rate in transfusion of packed erythrocytes.

The purpose of this prospective, randomized study was to measure both the independent and interactional effects of dilution, pressure, and apparatus on flow rates and hemolysis during rapid administration of erythrocytes. Administration of undiluted erythrocytes increased the concentration of plasma-free hemoglobin by as much as 270% per unit under certain conditions. Transfusion flow rates for packed red blood cells were found to be determined by dilution, pressure, and apparatus and varied by as much as 450%. No significant correlation was found between flow rate and hemolysis. Regardless of the external bag pressure applied or the transfusion apparatus used, packed erythrocytes should be diluted (with at least 100 ml of normal saline) to decrease hemolysis and increase flow rate.

Comparison of high-frequency jet ventilation with conventional mechanical ventilation in saline-lavaged rabbits

A surfactant-depletion lung-injury model was produced in 37 New Zealand white rabbits by saline lavage. During the next 2 to 3 h, rabbits were ventilated with conventional mechanical ventilation (CMV, group 1), high-frequency jet ventilation (HFJV, group 2), or CMV for 1 h followed by HFJV for 2 h (CMV/HFJV, group 3). Survival until planned termination of the protocol was 56%, 77%, and 63% in groups 1, 2 and 3, respectively. Causes of early demise were usually pneumothorax or metabolic acidosis. There were no statistically significant differences among the groups with respect to survival, incidence of pneumothorax or metabolic acidosis. Arterial oxygenation was more efficient with HFJV (group 2) (P[A-a]O2 = 372 ± 51 torr [mean ± SE] at 2 h) than with CMV (group 1) (P[A-a]o2 = 512 ± 18 torr at 2 h, p < .01). Furthermore, oxygen gas exchange in 3 of 5 group 3 rabbits improved after institution of HFJV. In contrast to previous findings with high-frequency oscillation (HFO), there were no qualitative histologic differences between lungs ventilated with HFJV vs. CMV. Thus, although HFJV produced more efficient gas exchange in this model, it did not improve pulmonary pathology. HFO may be preferable to HFJV in infant respiratory distress syndrome.

Jet pulse characteristics for high-frequency jet ventilation in dogs.

High-frequency jet ventilation (HFJV) delivers pulsed gas streams to the airway either via small diameter catheters placed inside or via a lumen contained within the wall of a tracheal tube (1-3). Pulsation of the HFJV source gas is typically produced by either electronic-controlled solenoid valves or fluidic systems that can provide precise regulation of the pulsed gas stream (1-7). Frequencies may be independently prescribed or electronically coupled to the cardiac QRS complex (5, 6). HFJV reportedly provides efficient ventilation at peak airway pressures and tidal volumes significantly less than those required for conventional ventilation (8). Effectiveness of HFJV has been correlated with high flow amplitude, high initial inspiratory flow, and sufficient expiratory time (I/E) 2 0.3) (7). The purpose of this study was to investigate highfrequency jet characteristics upon ventilation efficiency using constant gas inlet pressures in dogs. Effects of the solenoid-controlled independent variables (pulse duration, frequency, and wave shape) were observed upon dependent variables [airway peak pressure, positive end-expiratory pressure (PEEP),

Airway pressure as a measure of gas exchange during high-frequency jet ventilation

Airway pressure during high-frequency jet ventilation (HFJV) reflects safety, ventilator performance, and gas exchange. The value of airway pressure as a monitoring and control variable for predicting the effectiveness of gas exchange was examined in 2 studies using healthy dogs. In the first study, HFJV was delivered to the airway via an extra lumen in the wall of an endotracheal tube, at a frequency of 150 cycle/min and 30% inspira-tory time. Airway pressures (peak, mean, trough) were measured at various locations, from 5 cm below to 30 cm above the jet port. Pressures measured above the jet were misleading, but the proper measurement distance below the jet remains uncertain. The second study used the same ventilator settings but varied the airway pressure difference between peak and end-expiratory pressures (2, 4, or 6 cm H2O), and either the mean airway pressure (6 or 10 cm H2O) or the positive end-expiratory pressure (0, 5, 10, or 15 cm H2O). The airway pressure difference correlated strongly with efficiency of gas exchange for both CO2 elimination and oxygenation. Mean and end-expiratory pressures showed little influence over moderate ranges, but use of 15 cm H2O of PEEP decreased efficiency of both CO2 elimination and oxygenation, presumably due to increased dead space because of lung overdistension. We conclude that the airway pressure difference, measured as far distal in the airway as is safe and practical, can be useful for monitoring and controlling HFJV.

Response of lower esophageal contractility to changing concentrations of halothane or isoflurane: A multicenter study

A multiple-center study was performed to determine the relationship between lower esophageal contractility, clinical signs, and anesthetic concentration as expressed by minimum alveolar concentration (MAC). One hundred four American Society of Anesthesiologists Class I through III patients were exposed to isoflurane (with and without nitrous oxide) or halothane in concentrations of 0.5, 1.0, and 1.5 MAC. Heart rate and systolic blood pressure were continuously monitored. Both the amplitude and frequency of spontaneous and provoked lower esophageal contractions were measured in situ by using a 24-F probe equipped with provoking and measuring balloons. Combined results demonstrated statistically significant correlations (P<0.001) between lower esophageal contractility and MAC. Spontaneous lower esophageal contractions decreased from 1.10±0.12 (SEM) contractions per minute (0.5 MAC) to 0.42±0.05 (1 MAC) to 0.18±0.05 (1.5 MAC). Provoked lower esophageal contractility values decreased from 45±4 mm Hg (0.5 MAC) to 29±3 (1 MAC) to 19±2 (1.5 MAC). Heart rate changes did not correlate with MAC, and systolic blood pressure correlated in only one of three centers. Intracenter and intercenter analyses failed to demonstrate a significant relationship between lower esophageal contractility and heart rate or systolic blood pressure. No intracenter differences in either amplitude or frequency of lower esophageal contractions were observed, despite differences in volatile agents, induction techniques and agents, patient populations, and duration of anesthesia. Our studies indicate that lower esophageal contractility may be an indicator of anesthetic depth as reflected by MAC, but further studies are needed to quantify the effects of surgical stimulus, intravenous anesthetics, vasodilators, anticholinergics, calcium channel blockers, beta-adrenergic agonists, and the presence of a nasogastric tube.

Evaluation of peripheral nerve stimulators and relationship to possible errors in assessing neuromuscular blockade

Voltage and current output characteristics were measured on six commercially available peripheral nerve stimulator devices. The results are evaluated as possible sources of variability in peripheral nerve stimulator function and neuromuscular blockade assessment. The authors found significant differences in output voltage waveform and in maximum current into a 470 ohm load (21.4 to 128 mA.). Output current decreased from 25 to 88% in the different devices, with a load impedance increase from 470 to 10,000 ohms. Due to the variability in peripheral nerve stimulation units and the decrease in current output at higher load impedance, less than supramaximal stimulation is possible with erroneous interpretation of neuromuscular blockade.