Desflurane and isoflurane produce similar alterations in systemic and pulmonary hemodynamics and arterial oxygenation in patients undergoing one-lung ventilation during thoracotomy.

UNLABELLED: We tested the hypothesis that desflurane (DES) and isoflurane (ISO) produce similar effects on systemic and pulmonary hemodynamics and arterial oxygenation before, during, and after one-lung ventilation (OLV) in patients undergoing thoracotomy. After obtaining informed consent, anesthesia was induced with sodium thiopental or thiamylal, fentanyl, and vecuronium in 61 ASA physical status II-IV patients. Patients were randomly assigned to receive either DES (n = 30) or ISO (n = 31) in 100% O2 in separate groups. Hemodynamic data (radial and pulmonary artery [PA] catheters) were recorded, and blood gas values were obtained before and after induction; at selected intervals before, during, and after OLV; and before emergence. DES significantly (P < 0.05) increased heart rate (HR) and decreased mean arterial pressure (MAP) and cardiac output (CO). PA pressures and pulmonary vascular resistance (PVR) increased; systemic vascular resistance (SVR) was unchanged. Increases in HR and CO and decreases in MAP and SVR occurred during OLV and DES. Reductions in PaO2 (411 +/- 88 to 271 +/- 131 mm Hg 5 min after beginning OLV; mean +/- SD) and content (CaO2) and increases in shunt fraction (Qs/Qt; 0.25 +/- 0.12 to 0.40 +/- 0.19 at 5 min after beginning OLV) were also observed. ISO increased HR and PA pressures but did not alter MAP, CO, and PVR, in contrast to the findings with DES. Reductions in MAP and SVR and increases in CO and PA pressures were observed during OLV in the presence of ISO. Similar to the findings during DES, decreases in PaO2 and CaO2 and increases in Qs/Qt occurred during OLV and ISO. We conclude that DES and ISO produce very similar alterations in systemic and pulmonary hemodynamics and arterial oxygenation in patients undergoing OLV during thoracotomy. IMPLICATIONS: Desflurane and isoflurane produce similar cardiovascular and pulmonary effects before, during, and after one-lung ventilation in patients undergoing lung surgery.

Safety and potency of ANQ 9040 in male volunteers.

BACKGROUND: ANQ 9040 is an experimental nondepolarizing neuromuscular relaxant. Initial investigations in animals had indicated a rapid onset of action comparable to that of succinylcholine. The purpose of this study was to assess the safety and potency of ANQ 9040 in humans. METHODS: ANQ 9040 was assessed in 41 male volunteers. Anesthesia was induced with propofol and maintained with a propofol infusion and 60% N2O/40% O2. Neuromuscular function was measured by mechanomyography using train-of-four stimulation of the ulnar nerve every 12 s. After an initial pilot study, 23 volunteers received a single dose of ANQ 9040 of between 0.5 and 1.1 mg/kg to determine the dose-response relationship. The final 10 volunteers were given twice the estimated ED95 of ANQ 9040 as a single bolus dose. RESULTS: The estimated ED50 and ED95 of ANQ 9040 were 0.6 and 1.3 mg/kg, respectively. Apart from an increase in heart rate, no important adverse effects were noted after ANQ 9040 administration in the dose range 0.5-1.1 mg/kg. In the volunteers who received 2.6 mg/kg ANQ 9040, a substantial increase in plasma histamine was observed. This was associated with a 12% decrease in mean arterial pressure and a 49% increase in heart rate. In this group, the mean onset time to neuromuscular block was 51.3 s. CONCLUSIONS: ANQ 9040 is a rapid-onset neuromuscular blocking agent. However, twice the ED95 dose is associated with significant histamine release and tachycardia. This finding suggests that this drug will not be useful in clinical practice.

Clinical characteristics of desflurane in surgical patients: minimum alveolar concentration.

Desflurane (formerly I-653) is a new inhalaticnal anesthetic with a promising pharmacokinetic profile that includes low solubility in blood and tissue, including fat. Since its lipid solubility is less than that of other volatile agents, it may have lower potency. Low solubility would be expected to increase the rate at which alveolar concentration approaches inspired concentration during induction as well as to increase the rate of elimination of desflurane from blood at emergence. We determined the minimum alveolar concentration (MAC) of desflurane in 44 unpremedicated ASA physical status 1 or 2 patients undergoing elective surgery. We prospectively studied four patient groups distinguished by age and anesthetic regimen: 18-30 versus 31-65 yr and desflurane in 60% N2O/40% O2 versus desflurane in O2. Anesthesia was induced with desflurane or desflurane in 60% N2O/40% O2. MAC was determined by a modification of Dixon's up-and-down method with increments of 0.5% desflurane. The MAC of desflurane in O2 was 7.25 +/- 0.0 (mean +/- SD) in the 18-30-yr age group, and 6.0 +/- 0.29 in the 31-65-yr group; the addition of 60% N2O reduced the MAC to 4.0 +/- 0.29 and 2.83 +/- 0.58, respectively. The median time from discontinuation of desflurane to an appropriate response to commands was 5.25 min. Desflurane appears to be a mild airway irritant but was well tolerated by all patients.

Biotransformation and hepato-renal function in volunteers after exposure to desflurane (I-653).

Ten healthy unpremedicated male volunteers were exposed to an average inspired concentration of 3.6% desflurane (I-653) in oxygen for 89 (SD 17) min. Standard haematological and biochemical tests were performed before (control) and immediately after exposure and at 4, 24, 72 and 192 h. Liver function was assessed at these times by determining total and unconjugated (indirect) bilirubin, and plasma concentrations of aspartate amino transferase, alanine amino transferase, gamma-glutamyl transpeptidase and alkaline phosphatase. Renal function was assessed by examining the urine microscopically for leucocytes, red blood cells, casts and crystals at these times, and creatinine clearance and urine concentrating ability were determined before and 24 and 72 h after exposure. Two additional and sensitive tests of renal integrity were performed before and 4 and 24 h after anaesthesia: measurement of urinary retinol-binding protein and beta-N-acetyl-D-glucosaminidase. Serum inorganic fluoride was determined immediately before and 1, 4, 24, 48, 72 and 192 h after anaesthesia. Urinary inorganic and organic fluoride concentration and excretion rate were determined before and 24, 48, and 72 h after anaesthesia. There were no significant changes in any measured haematological or biochemical variable (other than an increase in total white cell count from 5.9 (1.3) to 8.3 (1.1) x 10(9) litre-1 immediately after exposure) nor in liver or renal function tests. There was no increase in serum or urinary inorganic fluoride or urinary non-volatile organic fluoride concentrations.

General versus epidural anesthesia for femoral-popliteal bypass surgery.

This study examines whether epidural anesthesia is more effective than general anesthesia using an inhalation agent in controlling cardiovascular responses during femoral-popliteal bypass surgery. Nineteen patients were randomized into two groups: general anesthesia (n = 10) and epidural anesthesia (n = 9). The patients who underwent general anesthesia received sodium pentothal and succinylcholine for induction of anesthesia and 60% N2O, 40% O2, and 1% to 1.5% isoflurane for maintenance. Fifteen minutes before extubation, the patients received morphine sulfate 0.05 mg/kg intravenously (IV). The group that underwent epidural anesthesia received anesthesia to T-10 (through a catheter placed in the L4-5 interspace using 3% 2-chloroprocaine). Thirty minutes after the last dose, 0.05 mg/kg IV was administered. Hemodynamic variables were recorded at selected intervals during the operation and for 60 minutes in the recovery room. In the general anesthesia group, mean arterial pressure (MAP) and rate pressure product (RPP) significantly decreased (p less than 0.05) during the operation as compared with preoperative values. Following intubation and skin incision, 5 minutes after extubation, and after 60 minutes in the recovery room, MAP, heart rate (HR), and RPP were significantly greater (p less than 0.05) as compared with intraoperative periods. In the epidural anesthesia group, there were clinically important decreases in MAP and RPP after reaching T-10 and skin incision. The general anesthesia patients showed higher MAP, HR, and RPP 5 minutes after extubation and after 60 minutes in the recovery room. Epidural anesthesia patients showed stable hemodynamic patterns throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetics and potency of desflurance (I-653) in volunteers.

The inhalation anesthetic, desflurance (I-653), is a methyl ethyl ether halogenated entirely with fluorine and differing from isoflurance only in the substitution of fluorine for chlorine on the alpha-ethyl carbon. Relative to presently used potent inhalation anesthetics, desflurane has low blood/gas (0.42) and oil/gas (18.7) partition coefficients. These indicate that it will undergo rapid washin and washout (and hence rapid induction of and recovery from anesthesia) and have a MAC value of about 5%. In the present study we demonstrate that desflurane possesses these characteristics in healthy young volunteers. After a 10-min exposure to desflurane the ratio of alveolar (FA) (determined by end-tidal sampling) to inspired (FI) concentration (FA/FI) was 0.82. Washout was similarly rapid; 10 min after discontinuing administration of desflurane, the alveolar concentration relative to the last concentration during administration of anesthetic (FAO) was 0.11 (FA/FAO). These values are similar to those for nitrous oxide. Volunteers responded to commands an average of 2.7 min after discontinuing anesthetic administration. The values for MAC-awake and MAC (the latter determined by tetanic stimulation of the ulnar nerve using surface electrodes) were 2.42% and 4.58% and the ratio of the former to the latter was 0.53.

Is sufentanil removed by blood conservation devices?

To conserve blood during open heart surgery, cell savers and hemoconcentrators are used. Cell savers retrieve and filter shed blood from the operative field and then wash and separate reconcentrated erythrocytes from a supernatant by centrifugation. Hemoconcentrators are extracorporeal devices that extract an ultrafiltrate from the circulating perfusate during cardiopulmonary bypass. Both cell saver supernatant and hemoconcentrator ultrafiltrate are discarded. Twenty patients were anesthetized with a single dose of sufentanil, 30 microg/kg, and the cell saver supernatant and hemoconcentrator ultrafiltrate were analyzed for sufentanil. The supernatant contained only 0.1% of the total administered dose. Hemoconcentrators from two different manufacturers were tested, and 0.1% of the administered sufentanil was detected in one ultrafiltrate and none was found in the other. Thirty minutes after induction of anesthesia, the plasma sufentanil concentration was 8.5 ng/mL (1.3% of the given dose); 1 hour later, it was 4.9 ng/mL (0.8%). During cardiopulmonary bypass, the plasma level decreased to 2.5 ng/mL (0.6%); after bypass, it fell to 1.5 ng/mL (0.3%). It is concluded that intravenous (IV) sufentanil rapidly leaves the plasma compartment, and little remains available to be extracted by the devices used to process and conserve blood.

Do oxygen consumption and carbon dioxide production affect cardiac output after cardiopulmonary bypass?

This study examines the oxygen consumption (VO2) and carbon dioxide production (VCO2) occurring before, during, and after cardiopulmonary bypass (CPB) and whether they correlate with changes in cardiac output. Twenty-three patients undergoing open heart surgery were studied. Group 1 (N = 11) received fentanyl citrate, 50 micrograms/kg, intravenously during the induction of anesthesia. Group 2 (N = 12) received 100 micrograms/kg of fentanyl citrate intravenously. We measured VO2, VCO2, as well as hemodynamic and biochemical factors. Initial statistical analyses failed to show any differences in the VO2, VCO2, hemodynamic, or biochemical factors between groups 1 and 2. Therefore, the data from both groups were combined. In comparing the average (for all data) of the post-CPB with the pre-CPB periods in both groups for the metabolic factors, there were 9.0%, 11.5%, and 2.4% increases in the VO2, VCO2, and respiratory quotient, respectively. There was an 80% increase in total serum lactate levels seen in the post-CPB periods when compared with the pre-CPB periods. Serum triglyceride and free fatty acid levels measured in the post-CPB period decreased 39% and 25%, respectively, when compared with the pre-CPB periods. Although there were no changes in the cardiac outputs following CPB, the post-CPB periods showed a 37% increase in central venous pressure when compared with the pre-CPB periods. These data suggest that although there are significant metabolic and biochemical sequelae to CPB, the modest increases in post-CPB VO2, and VCO2 did not affect cardiac output following cardiovascular surgery. Increasing doses of narcotic do not have an effect on those relationships.

Energy measurements and requirements of critically ill patients.

The energy expenditure of the critically ill patient is influenced by many factors, thus making it difficult to predict. Measurement of energy expenditure in mechanically ventilated patients receiving elevated oxygen concentrations requires a good understanding of the measurement technique and its limitations, whether it be the gas exchange or Fick method. More investigation is needed to better understand the determinants of energy expenditure, as well as the total energy requirements of the critically ill patient.

Response to tubular airway resistance in normal subjects and postoperative patients.

Critically ill patients must often breathe spontaneously through an endotracheal tube that acts as a fixed inspiratory and expiratory tubular airway resistor. Although this practice is common, its effect on the pattern of breathing is not known. The mean breathing patterns of seven normal, healthy male subjects and eight male patients who had undergone upper abdominal surgery 2-4 days previously were studied breathing through a mouthpiece fitted in random order with a 5, 6, 7, 8, or 15 mm diameter (17 mm long) resistor. These diameters were selected because they simulate the pressure-flow relationships of adult endotracheal tubes. With the 15 mm aperture, the patients had a greater breathing frequency (f) than did the normal subjects (21 +/- 5 [SD] vs. 14 +/- 4 breaths/min, P less than 0.01) as well as a smaller mean tidal volume (VT). In both groups, minute ventilation (VE) and f progressively decreased as resistance was increased by decreasing the aperture size from 15 to 16 mm. In the normal subjects but not the patients, VT also progressively decreased. When the diameter was decreased from 6 mm to 5 mm, there were increases in VT and decreases in f that were more marked in the normal subjects. In both groups, the changes in VE were accompanied by decreases in mean and peak inspiratory and expiratory flow rates. Throughout the study, oxygen consumption (VO2) and carbon dioxide production (VCO2) did not change. This, coupled with the decreases in VE resulted in decreases in the ventilatory equivalents to CO2 and O2 (VE/VCO2, VE/VO2).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of a non-invasive method for the measurement of metabolic rate in humans.

Measurements of oxygen consumption (VO2) and carbon dioxide production (VCO2) can be used to calculate energy expenditure. Such data are useful in the nutritional management of a variety of pathological conditions. This study is an evaluation in vitro and in vivo of the mating of a canopy and a Beckman metabolic measurement cart 1 (MMC). The canopy allows for the collection of expired gases without facial attachments. Studies in vitro demonstrated the necessity of calibrating the CO2 analyser at the concentrations used in such a system (0.50-0.80% CO2). Measurements of VO2 were within + 12% to -8% of predicted values, and when calibrated at 0.50% and 0.75% CO2, measurements of VCO2 were within + 2% and -7% of predicted values. The studies in vivo revealed that VO2 and VCO2 were within +/- 11% of the values obtained by using a canopy-spirometer-computer system. The MMC plus canopy may provide an alternative method for the clinical measurement of VO2 and VCO2, especially in subjects unable to tolerate a tight-fitting mask for prolonged periods.

Effect of routine intensive care interactions on metabolic rate.

The alterations in metabolic (oxygen consumption [VO2] and carbon dioxide production [VCO2]) and hemodynamic (heart rate and blood pressure) parameters caused by various common intensive care activities were examined in a group of 23 mechanically-ventilated critically-ill patients. The observed variations in metabolic rate can be classified into four categories as follows: (a) the lowest energy expenditure, which was associated with sleeping in the majority (83 percent) of instances; (b) resting, which was defined as a state where the patient was lying motionless with eyes open and responding to surrounding events, where VO2 and VCO2 averaged 9.1 +/- 7.5(SD) percent and 7.5 +/- 7.3 percent, respectively, above the lowest values; (c) a variety of routine daily care activities (eg, bathing, performing a physical examination) that although not particularly painful, caused arousal from the resting state. During these situations, VO2 and VCO2 averaged about 20 percent above lowest values; and (d) chest physical therapy, which was associated with metabolic increases of 35 percent above lowest values as well as increases in both heart rate and blood pressure. This study demonstrates that routine daily ICU activities can significantly alter metabolic rate, and thus, it is important to couple such measurements with astute observations of the patients' activity state. In addition, we have defined an activity state--resting--that can be used in the calculation of energy expenditure as well as for intrapatient and interpatient comparisons.

Abdominal aortic cross-clamping. Metabolic and hemodynamic consequences.

We address the question of whether an oxygen debt develops during a period of abdominal aortic cross-clamping that may explain observed hemodynamic changes. Group 1 received morphine sulfate (1 mg/kg) during induction of anesthesia. Group 2 received same dose of morphine sulfate. Group 3 received 4 mg/kg of morphine sulfate. We measured the oxygen consumption (VO2) and the carbon dioxide production levels (VCO2), as well as hemodynamic and biochemical parameters. In groups 1 and 3, VO2 and VCO2 decreased 10% to 13% following abdominal aortic cross-clamping compared with values measured before cross-clamping. In group 2, VO2 and VCO2 decreased 3% and 7%, respectively. On unclamping, the greatest increase in VO2 was observed in group 3 (26%), while in groups 1 and 2, VO2 rose 18% and 5%, respectively. In all three groups, metabolic changes were not paralleled by hemodynamic or temperature changes. Results indicate that oxygen debt developed during abdominal aortic cross-clamping, but this has no effect on hemodynamic changes seen after unclamping. Higher dosage of narcotic administered during anesthetic induction did not temper increase in metabolic rate observed after unclamping.

Morphine and postoperative rewarming in critically ill patients.

Morphine sulfate (MSO4) has been demonstrated to attenuate the stress response. MSO4 might be useful in minimizing the stress associated with the perioperative period, particularly that due to awakening from anesthesia and rewarming. Two groups of critically ill patients who developed hypothermia (35.8 degrees C) during a surgical procedure were studied. The control group was observed during routine medical management. Group II received 1 or 4 mg/kg MSO4 followed by an infusion of 0.2 or 0.5 mg/kg/hr. During the postoperative rewarming period the control group patients demonstrated a major increase in metabolic demand and myocardial work. In group II patients the infusion of MSO4 resulted in a lower metabolic rate. This was associated with a significantly longer rewarming time and a significant reduction in shivering, heat loss, heart rate, mean arterial pressure, and rate-pressure product. Infusion of MSO4 in critically ill patients during the perioperative period suppressed metabolic demands and myocardial work while preserving cardiovascular function.

Artifacts in measurement of resting energy expenditure.

Measurements of gas exchange have been demonstrated to be clinically useful in the care of critically ill and malnourished patients. Using principles of indirect calorimetry, resting energy expenditure (REE) can be calculated from gas exchange data and used as the basis for designing a nutritional support regimen as well as for following the patient's metabolic state. This study demonstrates that a relatively minor procedure, such as percutaneous muscle biopsy, can induce temporary but major increases in gas exchange and lead to an overestimation of REE. Four studies were performed on 3 healthy adult subjects admitted to the Surgical Metabolism Unit for nutritional study. A percutaneous muscle biopsy was performed with the subject inside a canopy with continuous recording of oxygen consumption (VO2) and carbon dioxide production (VCO2). After the muscle biopsy, VCO2 and VO2 increased 93 and 103% (at their peak value), respectively. The mean duration that these changes persisted at least 15% above control was 10.6 +/- 7.8 (SD) and 11.4 +/- 5.9 min of VCO2 and VO2, respectively. Thus, considerable artifacts in the estimation of REE can occur due to painful stimuli.

Physiologic requirements during rewarming: suppression of the shivering response.

Intraoperative hypothermia has become a common occurrence. Postoperative rewarming often is accompanied by shivering and results in increased metabolic and circulatory demands. We examined the metabolic, hemodynamic, and biochemical variables in 2 groups of hypothermic (greater than 35.8 degrees C) patients requiring mechanical ventilation after a major operation. One was observed during routine medical management whereas the other group received 40 mg of metocurine iodide and then observed during routine medical management. All patients were allowed to rewarm passively. O2 consumption (VO2, ml/min, STPD), CO2 production (VCO2, ml/min, STPD) and respiratory quotient (RQ) measurements were made every 15 min using a Beckman Metabolic Measurement Cart. Esophageal temperature, arterial blood pressure, heart rate (HR), rate pressure product, CVP, arterial blood gases, serum lactate concentration, and duration of shivering also were recorded. Suppression of the shivering by metocurine increased rewarming time significantly and decreased VCO2, VO2, HR, rate pressure product, mean arterial pressure (MAP), and the O2 cost of rewarming. Thus, the elimination of shivering during postoperative rewarming is associated with a decrease in caloric, metabolic demands and myocardial work (as assessed by the rate pressure product) while rewarming time is prolonged. In the postoperative, hypothermic, critically ill patient, suppression of the shivering response in selected patients may be indicated.

A systematic method for validation of gas exchange measurements.

The measurement of gas exchange is useful, but thus far, has not been practical during the mechanical ventilation of critically ill patients. To validate two new commercial instruments, (Siemens-Elema Servo Ventilator 900B, Beckman Metabolic Cart), the authors constructed a lung model into which they delivered CO2 and N2 at precise rates to simulate Co2 production (Vco2) and O2 consumption (Vos). The model consists of 13.5-1 gas jar with an attached one liter anesthesia bag. The lung model was ventilated at present tidal volumes and frequencies. The authors also compared the measured respiratory quotient (RQ) with the known RQ of burning methanol (RQ = 0.67) in the jar. When the model was ventilated with levels of tidal volume and gas exchange applicable to adults, both instruments measured V02 within 5 to 13% of predicted values. Varying the FI02 did not significantly affect this accuracy. At tidal volumes below 350 ml, the difference increased between predicted VCO2 and measured VCO2. The difference between measured vs. the actual RQ of methanol was 5 and 1.5% in the Siemens-Elema and Beckman Systems, respectively.