Effect of Halothane Anesthesia on Glucose Utilization and Production in Adolescents

Background: It should be possible to avoid variations in plasma glucose concentration during anesthesia by adjusting glucose infusion rate to whole-body glucose uptake. To study this hypothesis, we measured glucose utilization and production, before and during halothane anesthesia.

Methods: After an overnight fast, six adolescents between 12 and 17 yr of age were infused with tracer doses of [6,6-sup 2 H2]glucose for 2 h before undergoing anesthesia, and the infusion was continued after induction, until the beginning of surgery. Plasma glucose concentration was monitored throughout, and free fatty acids, lactate, insulin, and glucagon concentrations were measured before and during anesthesia.

Results: Despite the use of a glucose-free maintenance solution, plasma glucose concentration increased slightly but significantly 5 min after induction (5.3 plus/minus 0.4 vs. 4.5 plus/minus 0.4 mmol *symbol* 1 sup -1 , P < 0.05). This early increase corresponded to a significant increase in endogenous glucose production over basal conditions (4.1 plus/minus 0.4 vs. 3.6 plus/minus 0.2 mg *symbol* kg sup -1 *symbol* min sup -1, P < 0.05), with no concomitant change in peripheral glucose utilization. Fifteen minutes after induction, both glucose utilization and production rates decreased steadily and were 20% less than basal values by 35 min after induction (2.9 plus/minus 0.3 vs. 3.6 plus/minus 0.2 mg *symbol* kg sup -1 *symbol* min sup -1, P < 0.05). Similarly, glucose metabolic clearance rate decreased by 25% after 35 min. Despite the increase in blood glucose concentration, anesthesia resulted in a significant decrease in plasma insulin concentration.     

Effect of Vasoconstrictive Agents Added to Lidocaine on Intravenous Lidocaine-induced Convulsions in Rats

Background: Epinephrine is reported to decrease the threshold of intravenous lidocaine-induced convulsions. However, the mechanism underlying this effect is not clear. Therefore, we carried out a study to examine the role of vasopressor-induced hypertension.

Methods: Fifty-six awake Wistar rats were assigned to seven groups of eight. All groups received a continuous intravenous infusion of lidocaine at a rate of 4 mg *symbol* kg sup -1 *symbol* min sup -1 until generalized convulsions occurred. The control group (group C) received plain lidocaine. The acute hypertensive groups received lidocaine with epinephrine (group E), norepinephrine (group N), or phenylephrine (group P) to increase mean arterial blood pressure (MAP) to 150 plus/minus 5 mm Hg. Sodium nitroprusside (SNP) was added to prevent an increase in mean arterial pressure in the remaining three groups (vasopressor-SNP groups).

Results: The acute hypertensive groups required significantly smaller cumulative doses of lidocaine to produce convulsions compared with control (C - 41.5 plus/minus 2.9 > E - 24.1 plus/minus 2.7, N = 27.1 plus/minus 2.8, P = 26.7 plus/minus 2.5 mg *symbol* kg sup -1; values are mean plus/minus SD, P < 0.01) In addition, plasma lidocaine concentrations (C = 11.0 plus/minus 0.7 > E = 7.4 plus/minus 0.5, N = 7.9 plus/minus 0.6, P = 8.1 plus/minus 0.8 micro gram *symbol* ml sup -1, P < 0.01) and brain lidocaine concentrations (C = 50.9 plus/minus 4.5 > E = 32.6 plus/minus 4.2, N - 34.5 plus/minus 4.8, P - 37.1 plus/minus 4.5 micro gram *symbol* g sup -1, P < 0.01) were less in the acute hypertensive groups at the onset of convulsions. In the vasopressor-SNP groups, the plasma and brain lidocaine concentrations at the onset of convulsions returned to the control values, although epinephrine and norepinephrine, but not phenylephrine, still decreased cumulative convulsant doses of lidocaine significantly (P < 0.01) compared with control (E + SNP = 30.8 plus/minus 2.9 < N + SNP = 34.8 plus/minus 2.8, P < 0.01) < P + SNP = 40.2 plus/minus 3.0 mg *symbol* kg sup -1, P < 0.01). The brain/plasma concentration ratios were similar for the seven groups.     

pH-Stat Management Reduces the Cerebral Metabolic Rate for Oxygen during Profound Hypothermia (17 degrees Celsius): A Study during Cardiopulmonary Bypass in Rabbits

Background: Greater cerebral metabolic suppression may increase the brain's tolerance to ischemia. Previous studies examining the magnitude of metabolic suppression afforded by profound hypothermia suggest that the greater arterial carbon dioxide tension of pH-stat management may increase metabolic suppression when compared with alpha-stat management.

Methods: New Zealand White rabbits, anesthetized with fentanyl and diazepam, were maintained during cardiopulmonary bypass (CPB) at a brain temperature of 17 degrees Celsius with alpha-stat (group A, n = 9) or pH-stat (group B, n = 9) management. Measurements of brain temperature, systemic hemodynamics, arterial and cerebral venous blood gases and oxygen content, cerebral blood flow (CBF) (radiolabeled microspheres), and cerebral metabolic rate for oxygen (CMRO2) (Fick) were made in each animal at 65 and 95 min of CPB. To control for arterial pressure and CBF differences between techniques, additional rabbits underwent CPB at 17 degrees Celsius. In group C (alpha-stat, n = 8), arterial pressure was decreased with nitroglycerin to values observed with pH-stat management. In group D (pH-stat, n = 8), arterial pressure was increased with angiotensin II to values observed with alpha-stat management. In groups C and D, CBF and CMRO2 were determined before (65 min of CPB) and after (95 min of CPB) arterial pressure manipulation.

Results: In groups A (alpha-stat) and B (pH-stat), arterial pressure; hemispheric CBF (44 plus/minus 17 vs. 21 plus/minus 4 ml *symbol* 100 g sup -1 *symbol* min sup -1 [median plus/minus quartile deviation]; P = 0.017); and CMRO2 (0.54 plus/minus 0.13 vs. 0.32 plus/minus 0.10 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min sup -1; P = 0.0015) were greater in alpha-stat than in pH-stat animals, respectively. As a result of arterial pressure manipulation, in groups C (alpha-stat) and D (pH-stat) neither arterial pressure (75 plus/minus 2 vs. 78 plus/minus 2 mm Hg) nor hemispheric CBF (40 plus/minus 10 vs. 48 plus/minus 6 ml *symbol* 100 g sup -1 *symbol* min sup -1; P = 0.21) differed between alpha-stat and pH-stat management, respectively. Nevertheless, CMRO2 was greater in alpha-stat than in pH-stat animals (0.71 plus/minus 0.10 vs. 0.45 plus/minus 0.10 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min sup -1, respectively; P = 0.002).     

Evaluation of a recruitment maneuver with positive inspiratory pressure and high PEEP in patients with severe ARDS

BACKGROUND: To evaluate the effect of a recruitment maneuver (RM) with constant positive inspiratory pressure and high positive end-expiratory pressure (PEEP) on oxygenation and static compliance (Cs) in patients with severe acute respiratory distress syndrome (ARDS). METHODS: Eight patients with ARDS ventilated with lung-protective strategy and an arterial partial pressure of oxygen to inspired oxygen fraction ratio (PaO2/FIO2) < or =100 mmHg regardless of PEEP were prospectively studied. The RM was performed in pressure-controlled ventilation at FIO2 of 1.0 until PaO2 reached 250 mmHg or a maximal plateau pressure/PEEP of 60/45 cmH2O was achieved. The RM was performed with stepwise increases of 5 cmH2O of PEEP every 2 min and thereafter with stepwise decreases of 2 cmH2O of PEEP every 2 min until a drop in PaO2 >10% below the recruitment PEEP level. Data was collected before (preRM), during and after 30 min (posRM). RESULTS: The PaO2/FIO2 increased from 83 +/- 22 mmHg preRM to 118 +/- 32 mmHg posRM (P = 0.001). The Cs increased from 28 +/- 10 ml cmH2O(-1) preRM to 35 +/- 12 ml cmH2O(-1) posRM (P = 0.025). The PEEP was 12 +/- 3 cmH2O preRM and was set at 15 +/- 4 cmH2O posRM (P = 0.025). The PEEP of recruitment was 36 +/- 9 cmH2O and the collapsing PEEP was 13 +/- 4 cmH2O. The PaO2 of recruitment was 225 +/- 105 mmHg, with five patients reaching a PaO2 > or = 250 mmHg. The FIO2 decreased from 0.76 +/- 0.16 preRM to 0.63 +/- 0.15 posRM (P = 0.001). No major complications were detected. CONCLUSION: Recruitment maneuver was safe and useful to improve oxygenation and Cs in patients with severe ARDS ventilated with lung-protective strategy.     

Oral Clonidine Premedication Blunts the Heart Rate Response to Intravenous Atropine in Awake Children

Background: Clonidine, which is known to have analgesic and sedative properties, has recently been shown to be an effective preanesthetic medication in children. The drug may cause side effects, including bradycardia and hypotension. This study was conducted to evaluate the ability of intravenous atropine to increase the heart rate (HR) in awake children receiving clonidine preanesthetic medication.

Methods: We studied 96 otherwise healthy children, 8-13 yr old, undergoing minor surgery. They received, at random, oral clonidine 2 or 4 micro gram *symbol* kg sup -1 or placebo 105 min before scheduled induction of anesthesia. Part I (n = 48, 16 per group): When hemodynamic parameters after insertion of a venous catheter had been confirmed to be stable, atropine was administered in incremental doses of 2.5, 2.5, and 5 micro gram *symbol* kg sup -1 every 2 min. The HR and blond pressure were recorded at 1-min intervals. Part II (n = 48, 16 per group): After the recording of baseline hemodynamic values, successive doses of atropine (5 micro gram *symbol* kg sup -1 every 2 min, to 40 micro gram *symbol* kg sup -1), were administered until HR increased by 20 beats *symbol* min sup -1. The HR and blood pressure were recorded at 1-min intervals.

Results: Part I: The increases in HR in response to a cumulative dose of atropine 10 micro gram *symbol* kg sup -1 were 33 plus/minus 3%, 16 plus/minus 3%, and 8 plus/minus 2% (mean plus/minus SEM) in children receiving placebo, clonidine 2 micro gram *symbol* kg sup -1, and clonidine 4 micro gram *symbol* kg sup -1, respectively (P < 0.05). Part II: The HR in the control group increased by more than 20 beats *symbol* min sup -1 in response to atropine 20 micro gram *symbol* kg sup -1 or less. In two patients in the clonidine 4 micro gram *symbol* kg sup -1 group, HR did not increase by 20 beats *symbol* min sup -1 even after 40 micro gram *symbol* kg sup -1 of atropine.     

The Relation between Cerebral Metabolic Rate and Ischemic Depolarization: A Comparison of the Effects of Hypothermia, Pentobarbital, and Isoflurane

Background: Reductions in cerebral metabolic rate may increase the brain's tolerance of ischemia. However, outcome studies suggest that reductions in cerebral metabolic rate produced by anesthetics and by hypothermia may not be equally efficacious. To examine this question, we measured the effects of hypothermia, pentobarbital, and isoflurane on the cerebral metabolic rate for glucose (CMRG) and on the time to the loss of normal membrane ion gradients (terminal ischemic depolarization) of the cortex during complete global ischemia.

Methods: As pericranial temperature was varied between 39 and 25 degrees Celsius in normocapnic halothane-anesthetized rats, CMRG (using14 Carbon-deoxyglucose) or the time to depolarization (using a glass microelectrode in the cortex) after a Potassium sup + -induced cardiac arrest was measured. In other studies, CMRG and depolarization times were measured in normothermic animals (37.7 plus/minus 0.2 degree Celsius) anesthetized with high-dose pentobarbital or isoflurane (both producing burst suppression on the electroencephalogram) or in halothane-anesthetized animals whose temperatures were reduced to 27.4 plus/minus 0.3 degree Celsius. These three states were designed to produce equivalent CMRG values.

Results: As temperature was reduced from 39 to 25 degrees Celsius, CMRG decreased from 66 to 21 micro Meter *symbol* 100 g sup -1 *symbol* min1 (Q10 = 2.30), and depolarization times increased from 76 to 326 s. In similarly anesthetized animals at approximately 27 degrees Celsius, CMRG was 32 plus/minus 4 micro Meter *symbol* 100 g sup -1 *symbol* min sup -1 (mean plus/minus SD), whereas in normothermic pentobarbital- and isoflurane-anesthetized rats, CMRG values were 33 plus/minus 3 and 37 plus/minus 4 micro Meter *symbol* 100 g1 *symbol* min sup -1, respectively (P = 0.072 by one-way analysis of variance). Despite these similar metabolic rates, the times to depolarization were markedly different: for hypothermia it was 253 plus/minus 29 s, for pentobarbital 109 plus/minus 24 s, and for isoflurane 130 plus/minus 28 s (P < 0.0001).     

Myocardial Effects of Propofol in Hamsters with Hypertrophic Cardiomyopathy

Background: Propofol is a short-acting intravenous induction agent that induces cardiovascular depression but without significant effect no intrinsic myocardial contractility in various species. However, its effects on diseased myocardium remain unknown.

Methods: The effects of propofol (1, 3, and 10 micro gram *symbol* ml sup -1) on the intrinsic contractility of left ventricular papillary muscles from normal hamsters and those with hypertrophic cardiomyopathy (strain BIO 14.6, aged 6 months) were investigated in vitro (Krebs-Henseleit solution, 29 degrees Celsius, pH 7.40, Calcium sup +1 2.5 mmol *symbol* l [1], stimulation frequency 3/min).

Results: Cardiac hypertrophy (143 plus/minus 13%, P < 0.001) was observed in cardiomyopathic hamsters. The contractility of papillary muscles from hamsters with cardiomyopathy was less than that of controls, as shown by the decrease in maximum shortening velocity (29%, P < 0.03) and active isometric force (-51%, P < 0.03) and active isometric force (-51%, P < 0.001). Propofol did not induce any significant effect on contraction, relaxation, and contraction-relaxation coupling under low and high loads in normal hamsters. The effects of propofol were not significantly different between normal hamsters and those with cardiomyopathy. A slight but significant increase in maximum unloaded shortening velocity was observed in cardiomyopathic hamsters at 3 micro gram *symbol* ml sup -1 (4 plus/minus 6%, P < 0.05) and 10 micro gram *symbol* ml sup -1 (7 plus/minus 6%, P < 0.05).     

Influence of Gas Composition on Recurrence of Atelectasis after a Reexpansion Maneuver during General Anesthesia

Background: Atelectasis, an important cause of impaired gas exchange during general anesthesia, may be eliminated by a vital capacity maneuver. However, it is not clear whether such a maneuver will have a sustained effect. The aim of this study was to determine the impact of gas composition on reappearance of atelectasis and impairment of gas exchange after a vital capacity maneuver.

Methods: A consecutive sample of 12 adults with healthy lungs who were scheduled for elective surgery were studied. Thirty minutes after induction of anesthesia with fentanyl and propofol, the lungs were hyperinflated manually up to an airway pressure of 40 cmH2 O. FI sub O2 was either kept at 0.4 (group 1, n = 6) or changed to 1.0 (group 2, n = 6) during the recruitment maneuver. Atelectasis was assessed by computed tomography. The amount of dense areas was measured at end-expiration in a transverse plane at the base of the lungs. The ventilation-perfusion distributions (V with dot A/Q with dot) were estimated with the multiple inert gas elimination technique. The static compliance of the total respiratory system (Crs) was measured with the flow interruption technique.

Results: In group 1 (FIO2 = 0.4), the recruitment maneuver virtually eliminated atelectasis for at least 40 min, reduced shunt (V with dot A/Q with dot < 0.005), and increased at the same time the relative perfusion to poorly ventilated lung units (0.005 < V with dot A/Q with dot < 0.1; mean values are given). The arterial oxygen tension (PaO2) increased from 137 mmHg (18.3 kPa) to 163 mmHg (21.7 kPa; before and 40 min after recruitment, respectively; P = 0.028). In contrast to these findings, atelectasis recurred within 5 min after recruitment in group 2 (FIO2 = 1.0). Comparing the values before and 40 min after recruitment, all parameters of V with dot A/Q with dot were unchanged. In both groups, Crs increased from 57.1/55.0 ml *symbol* cmH2 O sup -1 (group 1/group 2) before to 70.1/67.4 ml *symbol* cmH2 O sup -1 after the recruitment maneuver. Crs showed as low decrease thereafter (40 min after recruitment: 61.4/60.0 ml *symbol* cmH2 O sup -1), with no difference between the two groups.     

Human Chest Wall Function while Awake and during Halothane Anesthesia: II. Carbon Dioxide Rebreathing

Background: Changes in the distribution of respiratory drive to different respiratory muscles may contribute to respiratory depression produced by halothane. The aim of this study was to examine factors that are responsible for halothane-induced depression of the ventilatory response to carbon dioxide rebreathing.

Methods: In six human subjects, respiratory muscle activity in the parasternal intercostal, abdominal, and diaphragm muscles was measured using fine-wire electromyography electrodes. Chest wall motion was determined by respiratory impedance plethysmography. Electromyography activities and chest wall motion were measured during hyperpnea produced by carbon dioxide rebreathing while the subjects were awake and during 1 MAC halothane anesthesia.

Results: Halothane anesthesia significantly reduced the slope of the response of expiratory minute ventilation to carbon dioxide (from 2.88 plus/minus 0.73 (mean plus/minus SE) to 2.01 plus/minus 0.45 l *symbol* min sup -1 *symbol* mmHg sup -1). During the rebreathing period, breathing frequency significantly increased while awake (from 10.3 plus/minus 1.4 to 19.7 plus/minus 2.6 min sup -1, P < 0.05) and significantly decreased while anesthetized (from 28.8 plus/minus 3.9 to 21.7 plus/minus 1.9 min sup -1, P < 0.05). Increases in respiratory drive to the phrenic motoneurons produced by rebreathing, as estimated by the diaphragm electromyogram, were enhanced by anesthesia. Anesthesia attenuated the response of parasternal electromyography and accentuated the response of the transversus abdominis electromyography to rebreathing. The compartmental response of the ribcage to rebreathing was significantly decreased by anesthesia (from 1.83 plus/minus 0.58 to 0.48 plus/minus 0.13 l *symbol* min sup -1 *symbol* mmHg sup -1), and marked phase shifts between ribcage and abdominal motion developed in some subjects. However, at comparable tidal volumes, the ribcage contribution to ventilation was similar while awake and anesthetized in four of the six subjects.     

The effect of timing of application of positive end-expiratory pressure on oxygenation during one-lung ventilation

Many studies have confirmed that applying positive end-expiratory pressure (PEEP) to the dependent lung during one-lung ventilation (OLV) improves oxygenation. Our purpose was to investigate the best time and level of PEEP application. Thirty patients undergoing thoracic surgery were randomised into three groups. After 20 minutes of two-lung ventilation (TLV) in the lateral position, all patients received OLV for one hour During OLV, 0, 5, 10 cmH2O PEEP were applied in order in group A, with each level sustained for 20 minutes. Group B had 5 cmH2O PEEP applied and maintained for one hour Patients in group C received PEEP with levels set in the opposite order to that of group A. The ventilation model was then converted to TLV. PaO2, PaCO2 and respiratory mechanical variables were compared at five different time points among groups, 20 minutes after TLV (T1), 20 (T2), 40 (T3) and 60 minutes (T4) after OLV and 20 minutes after conversion to TLV (T5). We found that PaO2 was lower in group A than the other two groups at T2 (P <0.05). PaO2 decreased significantly at T5 compared with T1 (P <0.05) in group A only. When PEEP was set to 10 cmH2O, the airway pressure increased significantly (P <0.05). These findings indicate that PEEP applied at the initial time of OLV improves oxygenation most beneficially. Five cmH2O PEEP may produce this beneficial effect without the increase in airway pressure associated with 10 cmH2O PEEP.     

Both lung recruitment maneuver and PEEP are needed to increase oxygenation and lung volume after cardiac surgery

BACKGROUND: Patients ventilated after cardiac surgery commonly have impaired oxygenation, mainly due to lung collapse. We have previously found that PaO2 and end-expiratory lung volume (EELV) were increased by a lung recruitment maneuver (LRM) followed by positive end-expiratory pressure (PEEP). The aim of this study was to evaluate whether only PEEP or only a LRM could give similar effects. METHODS: Thirty circulatory stable patients (aged 55-79 years) mechanically ventilated after cardiac surgery were randomized to receive LRM (four 10-s insufflations to an airway pressure of 45 cmH2O) and zero end-expiratory pressure (LRM-group), PEEP 12 cmH2O (PEEP-group) or LRM in combination with PEEP 12 cmH2O (LRM + PEEP-group). The set end-expiratory pressure was kept for 75 min. Before, during and after the intervention, EELV (SF6 washout technique) and blood gases were measured. RESULTS: Initial EELV and PaO2 were similar in all groups. In the LRM-group, PaO2 and EELV increased transiently (P < 0.0001), but returned at 5 min to the initial values. In the PEEP-group, PaO2 did not change but EELV increased to 155 +/- 27% of the initial value (P < 0.0001). In the LRM+PEEP-group, PaO2 and EELV increased to 212 +/- 66% and 178 +/- 31% of the initial values (P < 0.0001), respectively, and were maintained during PEEP application. CONCLUSION: In patients ventilated after cardiac surgery: (1) PEEP increased lung volume but not PaO2, (2) a lung recruitment maneuver without subsequent PEEP had no sustained effect, and (3) both a lung recruitment maneuver and PEEP were needed to increase and maintain the increased lung volume and PaO2.     

Effect of 7.2% Hypertonic Saline/6% Hetastarch on Left Ventricular Contractility in Anesthetized Humans

Background: Although a positive inotropic effect of hypertonic saline has been demonstrated in isolated cardiac tissue as well as in animal preparations, no information exists about a possible positive inotropic action of hypertonic saline in humans. The aim of this investigation was to determine whether a clinically relevant positive inotropic effect can be demonstrated in humans.

Methods: Twenty-six patients without cardiovascular disease were randomized to receive 4 ml/kg of either 7.2% hypertonic saline/6% hetastarch or 6% hetastarch (control) at a rate of 1 ml *symbol* kg sup -1 *symbol* min sup -1 while under general endotracheal anesthesia. Transesophageal echocardiography was used to evaluate left ventricular function. Arterial pressure, heart rate, and left ventricular end-systolic and end-diastolic diameter, area, and wall thickness were measured immediately before and after administration of either solution. Fractional area change, end-systolic wall stress, and the area under the end-systolic pressure-length relationship curve (ESPLRarea) were calculated. ESPLRarea was used to assess left ventricular contractility.

Results: Administration of hypertonic saline/hetastarch resulted in a significant decrease of mean arterial pressure and end-systolic wall stress from 77 plus/minus 14 (mean plus/minus SD) to 64 plus/minus 17 mmHg (P < 0.01) and from 52 plus/minus 14 to 32 plus/minus 11 103 dyne/cm2 (P > 0.01), respectively. End-diastolic area and fractional area change increased from 16.5 plus/minus 2.9 to 21.7 plus/minus 3.3 cm2 (P < 0.01) and from 0.53 plus/minus 0.07 to 0.70 plus/minus 0.06 (P < 0.01), respectively, whereas there was only a minor change of ESPLRarea from 38 plus/minus 13 to 44 plus/minus 13 mmHg.cm (P < 0.05).     

Effect of PEEP and inhaled nitric oxide on pulmonary gas exchange during gaseous and partial liquid ventilation with small volumes of perfluorocarbon

BACKGROUND: Partial liquid ventilation, positive end-expiratory pressure (PEEP) and inhaled nitric oxide (NO) can improve ventilation/perfusion mismatch in acute lung injury (ALI). The aim of the present study was to compare gas exchange and hemodynamics in experimental ALI during gaseous and partial liquid ventilation at two different levels of PEEP, with and without the inhalation of nitric oxide. METHODS: Seven pigs (24+/-2 kg BW) were surfactant-depleted by repeated lung lavage with saline. Gas exchange and hemodynamic parameters were assessed in all animals during gaseous and subsequent partial liquid ventilation at two levels of PEEP (5 and 15 cmH2O) and intermittent inhalation of 10 ppm NO. RESULTS: Arterial oxygenation increased significantly with a simultaneous decrease in cardiac output when PEEP 15 cmH2O was applied during gaseous and partial liquid ventilation. All other hemodynamic parameters revealed no relevant changes. Inhalation of NO and instillation of perfluorocarbon had no additive effects on pulmonary gas exchange when compared to PEEP 15 cmH2O alone. CONCLUSION: In experimental lung injury, improvements in gas exchange are most distinct during mechanical ventilation with PEEP 15 cmH2O without significantly impairing hemodynamics. Partial liquid ventilation and inhaled NO did not cause an additive increase of PaO2.     

Propofol Linearly Reduces the Vasoconstriction and Shivering Thresholds

Background: Skin temperature is best kept constant when determining response thresholds because both skin and core temperatures contribute to thermoregulatory control. In practice, however, it is difficult to evaluate both warm and cold thresholds while maintaining constant cutaneous temperature. A recent study shows that vasoconstriction and shivering thresholds are a linear function of skin and core temperatures, with skin contributing 20 plus/minus 6% and 19 plus/minus 8%, respectively. (Skin temperature has long been known to contribute [nearly equal] 10% to the control of sweating.) Using these relations, we were able to experimentally manipulate both skin and core temperatures, subsequently compensate for the changes in skin temperature, and finally report the results in terms of calculated core- temperature thresholds at a single designated skin temperature.

Methods: Five volunteers were each studied on 4 days: (1) control; (2) a target blood propofol concentration of 2 micro gram/ml; (3) a target concentration of 4 micro gram/ml; and (4) a target concentration of 8 micro gram/ml. On each day, we increased skin and core temperatures sufficiently to provoke sweating. Skin and core temperatures were subsequently reduced to elicit peripheral vasoconstriction and shivering. We mathematically compensated for changes in skin temperature by using the established linear cutaneous contributions to the control of sweating (10%) and to vasoconstriction and shivering (20%). From these calculated core-temperature thresholds (at a designated skin temperature of 35.7 degrees Celsius), the propofol concentration- response curves for the sweating, vasoconstriction, and shivering thresholds were analyzed using linear regression. We validated this new method by comparing the concentration-dependent effects of propofol with those obtained previously with an established model.

Results: The concentration-response slopes for sweating and vasoconstriction were virtually identical to those reported previously. Propofol significantly decreased the core temperature triggering vasoconstriction (slope = 0.6 plus/minus 0.1 degree Celsius *symbol* micro gram sup -1 *symbol* ml sup -1; r2 = 0.98 plus/minus 0.02) and shivering (slope = 0.7 plus/minus 0.1 degree Celsius *symbol* micro gram sup -1 *symbol* ml sup -1; r2 = 0.95 plus/minus 0.05). In contrast, increasing the blood propofol concentration increased the sweating threshold only slightly (slope = 0.1 plus/minus 0.1 degree Celsius *symbol* micro gram sup -1 *symbol* ml sup -1; r2 = 0.46 plus/minus 0.39).     

Pulsatile Versus Nonpulsatile Flow: No Difference in Cerebral Blood Flow or Metabolism during Normothermic Cardiopulmonary Bypass in Rabbits

Background: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees Celsius.

Methods: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees Celsius for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees Celsius. At 30 and 60 min of CPB, physiologic measurements were made as before.

Results: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 plus/minus 6 vs. 77 plus/minus 9 ml *symbol* 100 g sup -1 *symbol* min1, respectively (median plus/minus quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 plus/minus 0.5 vs. 4.1 plus/minus 0.6 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min1, respectively) and decreased slightly (0.4 plus/minus 0.4 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min1) between measurements.     

利用动态肺顺应性设定呼气末正压在胸腔镜肺叶切除术中的运用

目的 探讨单肺通气利用动态肺顺应性设定呼气末正压通气(positive end-expiratory pressure,PEEP)的优势及可行性. 方法 选择预行右侧肺叶切除患者80例,完全随机分为A组和B组,每组40例:A组,单肺通气实施肺膨胀(sustained inflation,SI)复张后加用20 cmH2O(1 cmH2O=0.098 kPa)的PEEP并递减滴定,随后以得到最大肺顺应性的PEEP值通气,直到恢复双肺通气;B组,通气PEEP值固定为5 cmH2O,其他通气方法同A组.记录患者血气、呼吸等参数. 结果 两组设定的PEEP值[A组(9.2±1.2) cmH2O,B组5 cmH2O]差异有统计学意义(P＜0.05);在单肺通气1 h(T3)、手术结束(T4)时,两组动脉血氧分压(partial pressure of oxygen,PaO2)比较,差异有统计学意义(P＜0.05);B组的PaO2在T3～T4逐步降低,差异有统计学意义(P＜0.05),而A组则维持较好(P＞0.05);T3、T4时刻A组的动态肺顺应性[(30.8±5.9)、(30.7±6.4) ml/cmH2O]与B组[(26.6±5.5)、(26.4±5.2) ml/cmH2O]比较,差异有统计学意义(P＜0.05). 结论 胸腔镜肺叶切除术中的单肺通气,利用动态肺顺应性设定的PEEP值通气能够得到更好的氧合及呼吸参数,并且维持较好.     

经胸腔镜肺大泡切除术中应用单肺通气对血气及血液动力学的影响

目的　观察胸腔镜手术中单肺通气时应用不同水平的呼气末正压通气 (PEEP)对血气及血液动力学的影响。方法　随机选择胸腔镜肺大泡切除术病人 36例 ,均分为三组 :A组为单肺间歇正压通气 (IPPV)通气 ;B组为单肺IPPV加PEEP 5cmH2 O通气 ;C组为单肺IPPV加PEEP10cmH2 O通气。分别记录平卧位双肺通气、侧卧位双肺通气、单肺通气 10min和 30min四个时点的血气和血液动力学参数。结果　各组病人SpO2 始终维持在 99%～ 10 0 %。动脉血氧分压 (PaO2 )也在正常范围 ,但B、C组明显高于A组 (P <0 .0 5 )。其余血气指标无明显变化。三组病人HR、MAP、左心室射血时间 (LVET)及体循环血管阻力 (SVR)均无明显变化。B、C组在单肺通气 10min及 30min后 ,每搏量 (SV)及心输出量 (CO)下降明显 ,但均在正常范围 ,且无组间差异。体位改变时血液动力学稳定。结论　经胸腔镜肺大泡切除术中单肺IPPV、PEEP 5cmH2 O均能维持满意的PaO2 和动脉血二氧化碳分压 (PaCO2 ) ,血液动力学变化不显著 ;但PEEP 5cmH2 O较IPPV能进一步提高PaO2 ,PEEP 10cmH2 O不能较PEEP 5cmH2 O进一步提高PaO2 。     

Protective Effect of Stroma-free Methemoglobin during Cyanide Poisoning in Dogs

Background: During fire exposure, cyanide toxicity can block aerobic metabolism. Oxygen and sodium thiosulfate are accepted therapy. However, nitrite-induced methemoglobinemia, which avidly binds cyanide, decreases oxygen-carrying capacity that is already reduced by the presence of carboxyhemoglobin (inhalation of carbon monoxide in smoke). This study tested whether exogenous stroma-free methemoglobin (SFmetHb) can prevent depression of hemodynamics and metabolism during canine cyanide poisoning.

Methods: In 10 dogs (weighing 18.8 plus/minus 3.5 kg) anesthetized with chloralose-urethane and mechanically ventilated with air, baseline hemodynamic and metabolic measurements were made. Then, 137 plus/minus 31 ml of 12 g% SFmetHb was infused into five dogs (SFmetHb group). Finally, the SFmetHb group and the control group (n = 5, no SFmetHb) received an intravenous potassium cyanide infusion (0.072 mg *symbol* kg sup -1 *symbol* min sup -1) for 20 min. Oxygen consumption (V with dot sub O2) was measured with a Datex Deltatrac (Datex Instruments, Helsinki, Finland) metabolic monitor and cardiac output (Q with dot T) was measured by pulmonary artery thermodilution.

Results: From baseline to cyanide infusion in the control group, Q with dot T decreased significantly (p < 0.05) from 2.9 plus/minus 0.8 to 1.5 plus/minus 0.4 l/min, mixed venous PCO2 (Pv with barCO2) tended to decrease from 35 plus/minus 4 to 23 plus/minus 2 mmHg, Pv with barO2 increased from 43 plus/minus 4 to 62 plus/minus 8 mmHg, V with dotO2 decreased from 93 plus/minus 8 to 64 plus/minus 19 ml/min, and lactate increased from 2.3 plus/minus 0.5 to 7.1 plus/minus 0.7 mM. In the SFmetHb group, cyanide infusion did not significantly change these variables. From baseline to infused cyanide, the increases in blood cyanide (4.8 plus/minus 1.0 to 452 plus/minus 97 micro Meter) and plasma thiocyanate cyanide (18 plus/minus 5 to 65 plus/minus 22 micro Meter) in the SFmetHb group were significantly greater than those increases in the control group. SFmetHb itself caused no physiologic changes, except small decreases in heart rate and Pv with barO2. Peak SFmetHb reached 7.7 plus/minus 1.0% of total hemoglobin.     

Correlation between extravascular lung water and oxygenation in ALI/ARDS patients in septic shock: possible role in the development of atelectasis?

This study aimed to evaluate the relationship between PaO2/FiO2 ratio and extravascular lung water in septic shock-induced acute respiratory distress syndrome in a prospective observational clinical trial. Twenty-three patients suffering from sepsis induced acute respiratory distress syndrome were recruited. All patients were ventilated in pressure control/support mode. Haemodynamic parameters were determined by arterial thermodilution (PiCCO) eight hourly for 72 hours. At the same time blood gas analyses were done and respiratory parameters were also recorded. Data are presented as mean +/-SD. For statistical analysis Pearson's correlation test, and analysis of variance (ANOVA) was used respectively. Significant negative correlation was found between extravascular lung water and PaO2/FiO2 (r = -0.355, P < 0.001), and significant positive correlation was shown between extravascular lung water and PEEP (r=0.557, P<0.001). A post-hoc analysis was performed when "low" PEEP: < 10 cmH2O and "high" PEEP: (10 cmH2O PEEP was applied, and neither the oxygenation, nor the driving pressure or the PaCO2 differed significantly, but the extravascular lung water showed significant difference when "high" or "low" PEEP was applied (13+/-5 vs 9+/-2 ml/kg respectively, P=0.001). This study found significant negative correlation between extravascular lung water and PaO2/FiO2. The mechanism by which extravascular lung water affects oxygenation is unknown but the significant positive correlation between PEEP and extravascular lung water shown in this trial suggests that the latter may have a role in the development of alveolar atelectasis.     

Propofol Fails to Attenuate the Cardiovascular Response to Rapid Increases in Desflurane Concentration

Background: A rapid increase in desflurane concentration to greater than 1 MAC transiently increases heart rate, arterial blood pressure, and circulating catecholamine concentration. Because propofol decreases sympathetic outflow, it was hypothesized that propofol would blunt these responses.

Methods: To test this hypothesis, five healthy male volunteers were studied three times. After induction of anesthesia with 2 mg *symbol* kg sup -1 propofol, anesthesia was maintained with 4% end-tidal desflurane in oxygen (0.55 MAC) via an endotracheal tube for 32 min. On separate occasions, in random order, either no propofol or 2 mg *symbol* kg sup -1 propofol was administered either 2 or 5 min before increasing end-tidal desflurane concentration from 4% to 8%.

Results: Without propofol pretreatment, the increase to 8% desflurane transiently increased heart rate (from 63+/-3 beats/min to 108 +/-5 beats/min, mean+/-SEM; P < 0.01), mean arterial pressure (from 73+/-1 mmHg to 118+/-6 mmHg; P < 0.01), and epinephrine concentration (from 14+/-1 pg *symbol* ml sup -1 to 279+/-51 pg *symbol* ml sup -1; P < 0.05). There was no significant change in norepinephrine concentration (from 198+/-37 pg *symbol* ml sup -1 to 277+/-46 pg *symbol* ml sup -1). The peak plasma epinephrine concentration was attenuated by each propofol pretreatment (158+/-35 pg *symbol* ml sup -1, propofol given 2 min before, and 146 + 41 pg *symbol* ml sup -1, propofol given 5 min before; P < 0.05), but neither propofol pretreatment modified the cardiovascular or norepinephrine responses.