Dose-related changes in the rate of cerebrospinal fluid formation and resistance to reabsorption of cerebrospinal fluid following administration of thiopental, midazolam, and etomidate in dogs

The rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption of CSF (Ra) were determined in dogs at four doses of thiopental (6, 12, 18, and 24 mg.kg-1.h-1), midazolam (0.5, 1.0, 1.5, and 2.0 mg.kg-1.h-1), and etomidate (0.86, 1.72, 2.58, and 3.44 mg.kg-1.h-1). Results were compared within and between groups and to previously reported normal values for Vf (0.030-0.054 ml/min) and Ra (220-240 cmH2O.ml-1.min) in dogs. At the two lower doses of thiopental, midazolam, or etomidate Vf was not significantly different than previously reported normal values. At the two higher doses of each drug Vf was 0.019-0.024 ml/min, significantly reduced compared to Vf at the two lower doses of each drug. The pattern of Ra data was more varied. With thiopental Ra was elevated at the lowest dose, (354 +/- 17 cmH2O.ml-1.min, mean +/- SD) reduced at the highest dose (156 +/- 19 cmH2O.ml-1.min), and not significantly different than previously reported normal values at the two intermediate doses. With midazolam Ra was elevated at the lowest and highest doses (332 +/- 25 and 378 +/- 18 cmH2O.ml-1.min) and normal at the two intermediate doses. With etomidate Ra was normal at the three lower doses and reduced at the highest dose (187 +/- 13 cmH2O.ml-1.min). It is concluded that CSF volume may be increased and the CSF pressure at which CSF volume contracts may be increased by doses of thiopental or midazolam that increase Ra, but not increased by etomidate.     

Rate of CSF formation and resistance to reabsorption of CSF during sevoflurane or remifentanil in rabbits

Information on the effects of sevoflurane on the rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption of CSF (Ra) is incomplete, and no such information is available for remifentanil. The present study examined the dose-related effects of sevoflurane and remifentanil on Vf and Ra in rabbits. Eight rabbits were studied during isoflurane 1.4% (baseline) and sevoflurane 1.4%, 2.5%, and 3.7%, and eight were studied during isoflurane 1.4% (baseline) and remifentanil 0.30, 0.67, and 1.00 microg x kg(-1) x min(-1) in randomized order. Ventriculocisternal perfusion at two CSF pressure states for each experimental condition was used to determine Vf and Ra. There was no dose-response relation for Vf (10.4+/-2.5, 9.0+/-2.0, and 10.0+/-3.0 microl x min(-1)) or Ra (0.81+/-0.33, 1.35+/-0.54, and 0.84+/-0.27 cm H2O x microl(-1) x min) between the three sevoflurane concentrations. There also was no dose-response relation for Vf (7.8+/-1.2, 8.8+/-3.0, and 6.5+/-2.3 microl x min(-1)) or Ra (1.07+/-0.54, 1.23+/-0.50, and 1.13+/-0.51 cm H2O x microl(-1) x min) between the three remifentanil doses. Vf and Ra during either sevoflurane or remifentanil were not significantly different from Vf and Ra during the two isoflurane baseline conditions (Vf = 8.5+/-2.5 and 9.8+/-1.3 microl x min(-1), and Ra = 0.97+/-0.36 and 1.38+/-0.55 cm H2O x microl(-1) x min, mean +/- SD). Vf and Ra are of interest because they influence CSF volume, intracranial pressure, and/or intracranial elastance. In our model, sevoflurane or remifentanil did not significantly alter Vf or Ra.     

Concentration-related changes in the rate of CSF formation and resistance to reabsorption of CSF during enflurane and isoflurane anesthesia in dogs receiving nitrous oxide

The rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption of CSF (Ra) were determined at four concentrations of enflurane (0.9, 1.8, 2.0, and 3.5% end-expired) or isoflurane (0.6, 1.1, 1.7, and 2.2% end-expired) in dogs receiving nitrous oxide (66%) in oxygen. At the two higher concentrations of enflurane, Vf was about 27% greater (38-40% greater when corrected for the effects of time) than at the two lower concentrations of enflurane. At the two lower concentrations of enflurane and at all doses of isoflurane, Vf did not differ between or within anesthetic groups (0.029-0.033 ml/min). The pattern of Ra data was more varied. Ra was elevated with the two lower concentrations of enflurane (by about 68%) and with isoflurane 1.1% (by about 33%), and reduced with the two higher concentrations of isoflurane (by about 14-17%). It is concluded that the effects of enflurane and isoflurane on CSF dynamics are concentration-related. All concentrations of enflurane studied favor CSF volume expansion, while high concentrations of isoflurane favor CSF volume contraction.     

Effects of halothane and fentanyl anesthesia on resistance to reabsorption of CSF

Using the technique of ventriculocisternal perfusion, resistance to reabsorption of cerebrospinal fluid (Ra) was examined in dogs during anesthesia with halothane (0.8%) or fentanyl (3.0 micrograms X kg-1 X min-1 for 20 minutes, followed by 0.2 micrograms X kg-1 X min-1, intravenously). Compared to normal Ra in dogs (220 to 224 cm H2O X ml-1 X min-1), halothane increased Ra to 245 +/- 2 cm H2O X ml-1 X min-1 (mean +/- standard error of the mean), and fentanyl decreased Ra to 114 +/- 1 cm H2O X ml-1 X min-1. Changes in Ra caused by halothane or fentanyl may contribute, in part, to changes in intracranial pressure (ICP) observed during prolonged anesthesia with these agents. Because decreased Ra improves spatial compensation by cerebrospinal fluid volume during increased ICP, fentanyl may be preferred over halothane in patients at risk because of increased ICP.     

Changes in the rate of formation and resistance to reabsorption of cerebrospinal fluid during deliberate hypotension induced with adenosine or hemorrhage.

Adenosine is recommended for induction of deliberate hypotension. Although its effects on brain vasculature and metabolism and intracranial pressure have been reported, its effects on cerebrospinal fluid dynamics have not. In this study the rate of cerebrospinal fluid formation (Vf), resistance to reabsorption of cerebrospinal fluid (Ra), and electroencephalogram (EEG) activity were determined in rabbits before and during decrease of cerebral perfusion pressure (CPP) with intravenous (iv) adenosine or hemorrhage. In the adenosine group (n = 6), Vf and Ra were determined at control CPP, at CPP of 50, 35, and 28 mmHg achieved with iv adenosine, and at CPP greater than 60 mmHg achieved with iv adenosine combined with iv phenylephrine. In the hemorrhage group (n = 6), Vf and Ra were determined at the first four experimental conditions only. Control values for Vf (9 +/- 3 and 9 +/- 4 microliter.min-1, mean +/- SD) and Ra (428 +/- 567 and 412 +/- 144 cmH2O.ml-1.min) did not differ between groups. In the adenosine group, Vf did not change significantly when CPP was decreased. However, in the hemorrhage group, Vf decreased significantly at CPP of 50 and 35 mmHg and became unmeasurable at CPP of 28 mmHg. Ra did not change significantly in either group. An increase of low-frequency (0.5-3.0 Hz) EEG activity and/or decrease of higher-frequency (3.5-30 Hz) EEG activity occurred at CPP of 28 mmHg in the adenosine group and at CPP of 35 mmHg in the hemorrhage group.(ABSTRACT TRUNCATED AT 250 WORDS)     

The rate of CSF formation, resistance to reabsorption of CSF, and aperiodic analysis of the EEG following administration of flumazenil to dogs

The effects of flumazenil, a benzodiazepine antagonist, on the rate of cerebrospinal fluid (CSF) formation (Vf), resistance to reabsorption of CSF (Ra) and the electroencephalogram (EEG) was determined in 12 dogs anesthetized with halothane (0.4%, end-expired) and nitrous oxide (66%, inspired) in oxygen. In six dogs the responses to flumazenil were measured during administration of midazolam (1.6 mg/kg followed by 1.25 mg.kg-1.h-1, intravenously) given along with inhalational anesthesia, whereas in the other six dogs the responses to flumazenil were measured during inhalational anesthesia without midazolam. Vf and Ra were determined using ventriculocisternal perfusion, and EEG activity was evaluated using aperiodic analysis. Flumazenil, 0.0025 and 0.16 mg/kg, was administered both when CSF pressure was normal and when CSF pressure was increased to 36-38 cmH2O by continuous infusion of mock CSF. Flumazenil produced no statistically significant change in Vf. Flumazenil did produce inconsistent and relatively small changes in Ra. Quantitative aperiodic analysis indicated changes in EEG activity only when the larger dose of flumazenil was given to dogs receiving midazolam. At normal CSF pressure the changes were consistent and were comprised of decreases in theta, alpha, and total hemispheric power. At elevated CSF pressure the changes were less consistent. It is concluded that smaller doses of flumazenil (which cause no EEG changes with the present method of analysis) and larger doses of flumazenil (which reverse midazolam-induced increase of theta and alpha activity) produce no change of Vf and no consistent change of Ra. Although flumazenil given in the presence of midazolam may increase Ra, thereby increasing CSF pressure and impairing contraction of CSF volume, this effect is not likely to be clinically important.     

Effects of halothane and fentanyl on the rate of CSF production in dogs

Using the open ventriculocisternal perfusion method, the rate of cerebrospinal fluid (CSF) production was examined in dogs anesthetized with either halothane (0.8%) or fentanyl (3.0 micrograms/kg/min for 20 min, then 0.2 micrograms/kg/min, intravenously), and nitrous oxide (60-70%) in oxygen. Halothane decreased the mean rate of CSF production from 0.047 +/- 0.006 ml/min (mean +/- SEM) in controls to 0.033 +/- 0.005 ml/min. This effect persisted throughout 3.0-3.5 h of anesthesia. When the expired concentration of halothane was decreased from 0.8% to less than 0.1%, the mean rate of CSF production returned to control values within 45-50 min. Fentanyl produced no change in the mean rate of CSF production compared to controls. These data suggest that increased CSF volume does not contribute to increased intracranial pressure during prolonged halothane anesthesia. In patients at risk for increased intracranial pressure due to increased CSF volume, either halothane or fentanyl may be preferable to anesthetics that may increase CSF production, e.g., enflurane.     

Isoflurane does not increase the rate of CSF production in the dog

Using the open ventriculocisternal perfusion method, the rate of cerebrospinal fluid (CSF) production was examined in dogs anesthetized with isoflurane (1.4%) and nitrous oxide (66%) in oxygen. In one group (n = 6) the rate of CSF production did not change significantly when the expired concentration was decreased from 1.4% to less than 0.15%. In a second group (n = 6) maintained at isoflurane 1.4%, the rate of CSF production decreased by approximately 8%/h, similar to the time effect previously reported in controls with this model (a decrease of 4-9%/h). These data suggest that isoflurane causes no significant change in the rate of CSF production and that an increase in CSF volume does not occur during prolonged isoflurane anesthesia. In patients at risk due to increased intracranial pressure, isoflurane may be preferred to anesthetics that may increase intracranial volume, e.g., enflurane or ketamine.     

Prolonged hypocapnia does not alter the rate of CSF production in dogs during halothane anesthesia or sedation with nitrous oxide

This study examined the effect of prolonged hypocapnia on the rate of cerebrospinal fluid (CSF) production (Vf) and on other CSF dynamics in dogs. Determination of CSF values began 2 h after the onset of hypocapnia and continued for an additional 3 h. Two separate methods were used to determine Vf: modified open ventriculocisternal perfusion and closed ventriculocisternal perfusion. Dogs were examined both during hypocapnia plus anesthesia with halothane (0.8%) and nitrous oxide (66%), and during hypocapnia plus sedation with nitrous oxide (66%) and halothane (0.15%) combined with bupivacaine (0.75%) infiltration of wound edges. There were no differences in Vf measured by the two methods. At the first measurable time period, mean Vf values during hypocapnia and halothane anesthesia, 32 +/- 9 and 35 +/- 10 microliters/min (mean +/- SD), were lower than mean Vf values during hypocapnia and nitrous oxide sedation, 48 +/- 11 and 49 +/- 8 microliters/min. Vf did not change significantly during 3 h of hypocapnia. For both halothane anesthesia and nitrous oxide sedation, mean Vf values during hypocapnia were not significantly different from Vf values previously reported during normocapnia, 31 +/- 12 and 33 +/- 12 microliters/min and 44 +/- 13 and 47 +/- 14 microliters/min, respectively. The results indicate that prolonged hypocapnia does not decrease Vf, and, therefore, reduction of Vf is probably not one of the causes for reduction of elevated CSF pressure by prolonged hypocapnia. Regarding the other data on CSF dynamics, CSF pressure at hypocapnia was similar to that at normocapnia, suggesting that hypocapnia did not affect resistance to reabsorption of CSF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle relaxation with succinylcholine or vecuronium does not alter the rate of CSF production or resistance to reabsorption of CSF in dogs

The open ventriculocisternal perfusion method was used to determine the rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption of CSF (Ra) in halothane-anesthetized dogs with and without succinylcholine (n = 6) and with and without vecuronium (n = 6). Both Vf and Ra during the use of either muscle relaxant were not different than Vf and Ra when no muscle relaxant was used. Succinylcholine caused muscle fasciculations and raised CSF pressure transiently (increase of 5.5 +/- 1.0 cm H2O [mean +/- SD]), while vecuronium did not. When muscle relaxants were not used, it became difficult to distinguish the effects of cardiovascular and respiratory activity on the CSF pressure waveform, and the coefficient of variability for determination of cisternal outflow rates was increased, making Ra values less reliable. It is concluded that continuous infusion of succinylcholine or vecuronium do not affect Vf or Ra. When Vf and Ra are determined by the method of ventriculocisternal perfusion, immobilization of respiratory muscles improves both the reliability of Ra values and the usefulness of the CSF pressure waveform. If a muscle relaxant is used, either succinylcholine or vecuronium would be suitable for such studies.     

Effects of sevoflurane on intracranial pressure and formation and absorption of cerebrospinal fluid in cats]

The effects of sevoflurane on intracranial pressure (ICP) and the formation and absorption of cerebrospinal fluid (CSF) were examined in cats. Changes in ICP and superior sagittal sinus pressure (SSSP) were studied for 180 minutes during anesthesia with 1MAC sevoflurane (2.6%, inspired) and 50% N2O in O2. ICP increased significantly immediately after the start of anesthesia. The level remained for the subsequent 120 minutes, but increased significantly again 140 minutes after the start of anesthesia. There was no change in SSSP. The rate of CSF formation (Vf) was examined using the open ventriculocisternal perfusion method during anesthesia for 180 minutes with 1MAC sevoflurane or 1MAC enflurane (2.4%, inspired) and 50% N2O in O2. During sevoflurane administration, Vf decreased significantly 30 minutes after the start of anesthesia. In contrast, during enflurane administration, Vf increased significantly 10 minutes after the start of anesthesia. Finally, Vf and the rate of CSF absorption (Va) were measured under 1MAC sevoflurane or 1MAC enflurane and 50% N2O in O2 anesthesia, or under 50% N2O in O2 anesthesia. They were compared with ICP level. Vf decreased significantly when ICP level increased in all groups. The increase in Va when ICP level increased, was greater in the N2O group than in those anesthetized with sevoflurane or enflurane. The delayed increase of ICP under sevoflurane may have resulted in part from the cranial accumulation of CSF due to increased resistance to CSF absorption.     

Dose-related changes in the rate of CSF formation and resistance to reabsorption of CSF during administration of fentanyl, sufentanil, or alfentanil in dogs

The rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption (Ra) of CSF were determined in dogs at four doses of fentanyl (0.05, 0.18, 0.60, and 3.0 microg.kg. min), sufentanil (0.01, 0.04, 0.13, and 0.60 microg.kg min) and aflentanil (1.4, 4.0, 13.0, and 40.0 microg.kg min). Results were compared within and between groups and to previously reported normal values (obtained during a variety of background anesthetics) for Vf (0.030-0.054 ml/min) and Ra (220-253 cm H2O ml min) in dogs. At the two lower doses of fentanyl and at all doses of sufentanil and alfentanil, Vf values were not significantly different from previously reported normal values. At the two higher doses of fentanyl, Vf decreased by 24 and 49%, respectively. At the two lower doses of all three drugs, Ra was significantly decreased, with mean values 40-52% below previously reported normal values. At the two higher doses of alfentanil, Ra values were not significantly different from previously reported normal values, and at the two higher doses of fentanyl and sufentanil, Ra was unchanged or increased. It is concluded that, among these three narcotics, reduction of CSF volume (as determined by the balance between Vf and Ra) is favored most by fentanyl, and ease of CSF volume contraction (as determined by Ra) is favored most by alfentanil.     

Intracranial volume-pressure relationship following thiopental or etomidate

A series of infusions of mock cerebrospinal fluid (CSF) was used to determine intracranial volume-pressure relationships in 18 anesthetized dogs. Measures of intracranial volume-pressure relationships included 1) CSF pressure prior to volume infusion (P0), 2) peak CSF pressure (Pp) caused by volume injection, 3) intracranial compliance (C, calculated as the ratio of change of intracranial volume [delta V] to change of CSF pressure [delta P]), 4) the volume-pressure response (VPR, a measure of elastance, calculated as the ratio of delta P to delta V), 5) the pressure volume index (PVI, calculated as the ratio of delta V to log Pp/P0), and 6) estimated intracranial compliance (Ce, calculated from PVI as 0.4343 PVI/P0). Six of the 18 dogs (time controls) were studied during halothane (0.4%, end expired) and nitrous oxide (66%) in oxygen, six dogs were studied prior to and following each of two doses of thiopental (approximate cumulative doses were 10.5 and 25.5 mg/kg), and six dogs were studied prior to and following each of two doses of etomidate (approximate cumulative doses were 1.52 and 3.70 mg/kg). In the time controls P0, Pp, C, VPR, PVI, and Ce were steady throughout the experimental period. Thiopental decreased P0 (by 2-3 +/- 1 cmH2O) and Pp (by 2-4 +/- 2 cmH2O), increased Ce (by 0.02-0.03 +/- 0.01 ml/cmH2O), and did not change C, VPR, or PVI. Etomidate decreased P0 (by 3-4 +/- 1 cmH2O) and Pp (by 4-6 +/- 2 cmH2O), increased Ce (by 0.03-0.04 +/- 0.01 ml/cmH2O) and did not change C, VPR, or PVI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. V. Role of pharmacokinetics and the autonomic nervous system in the interactions between verapamil and inhalational anesthetics

To assess the role of both pharmacokinetics and the autonomic nervous system in the interaction between inhalational anesthetics and verapamil, dogs were chronically instrumented to measure heart rate, PR interval, dP/dt, cardiac output, and aortic blood pressure. In a first group of seven dogs, studied awake and during halothane (1.2%), enflurane (2.5%), and isoflurane anesthesia (1.6%), verapamil was infused for 30 min in doses calculated to obtain similar plasma concentrations (83 +/- 10, 82 +/- 6, 81 +/- 10, and 77 +/- 9 ng.ml-1, respectively). For the latter purpose, the infusion dose was 3 and 2 micrograms.kg-1.min-1 awake and during anesthesia, respectively, preceded by a loading dose of 200, 150, and 100 micrograms.kg-1, awake, during isoflurane, and halothane and enflurane, respectively. In awake dogs, verapamil induced an increase in heart rate (24 +/- 5 bpm) and PR interval (35 +/- 9 msec) and a decrease in mean arterial pressure (-5 +/- 2 mmHg) and dP/dt (-494 +/- 116 mmHg/s). Although plasma concentrations were similar in awake and in anesthetized dogs, the only statistically significant changes induced by verapamil were an increase in heart rate and a decrease in dP/dt during halothane and enflurane, while left atrial pressure increased only with enflurane. In a second group of six dogs, verapamil pharmacokinetics were determined in the presence and absence of a ganglionic blocking drug (chlorisondamine, 2 mg.kg-1 iv). Blockade of ganglionic transmission resulted in a decrease in both initial volume of distribution and total clearance of verapamil--changes similar to those previously reported with inhalational anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)     

Desflurane and Isoflurane Increase Lumbar Cerebrospinal Fluid Pressure in Normocapnic Patients Undergoing Transsphenoidal Hypophysectomy

Background: Rapid emergence from anesthesia makes desflurane an attractive choice as an anesthetic for patients having neurosurgery. However, the data on the effect of desflurane on intracranial pressure in humans are still limited and inconclusive. The authors hypothesized that isoflurane and desflurane increase intracranial pressure compared with propofol.

Methods: Anesthesia was induced with intravenous fentanyl and propofol in 30 patients having transsphenoidal hypophysectomy with no evidence of mass effect, and it was maintained with 70% nitrous oxide in oxygen and a continuous 100 micro gram [centered dot] kg sup -1 [centered dot] min sup -1 infusion of propofol. Patients were assigned to three groups randomized to receive only continued propofol infusion (n = 10), desflurane (n = 10), or isoflurane (n = 10) for 20 min. During the 20-min study period, each patient in the desflurane and isoflurane groups received, in random order, two concentrations (0.5 minimum alveolar concentration [MAC] and 1.0 MAC end-tidal) of desflurane or isoflurane for 10 min each. Lumbar cerebrospinal fluid (CSF) pressure, blood pressure, heart rate, and anesthetic concentrations were monitored continuously.

Results: Lumbar CSF pressure increased significantly in all patients receiving desflurane or isoflurane. Lumbar CSF pressure increased by 5 +/- 3 mmHg at 1-MAC concentrations of desflurane and by 4 +/- 2 mmHg at 1-MAC concentrations of isoflurane. Cerebral perfusion pressure decreased by 12 +/- 10 mmHg at 1-MAC concentrations of desflurane and by 15 +/- 10 mmHg at 1-MAC concentrations of isoflurane. Heart rate increased by 7 +/- 9 bpm with 0.5 MAC desflurane and by 8 +/- 7 bpm with 1.0 MAC desflurane, and by 5 +/- 11 bpm with 1.0 MAC isoflurane. Systolic blood pressure decreased in all but the patients receiving 1.0 MAC desflurane. To maintain blood pressure within predetermined limits, phenylephrine was administered to six of ten patients in the isoflurane group (range, 25 to 600 micro gram), two of ten patients in the desflurane group (range, 200 to 500 micro gram), and in no patients in the propofol group. Lumbar CSF pressure, heart rate, and systolic blood pressure did not change in the propofol group.     

The influence of halothane and isoflurane on pulmonary collateral ventilation

The effects of halothane and isoflurane on hypocapnic increases in pulmonary collateral resistance were studied in dogs. A bronchoscope with a double lumen catheter in the suction port obstructed a peripheral airway and allowed gas to flow out of the isolated segment of lung only via collateral channels. The collateral gas flow (Vcoll) was measured with a flowmeter and delivered through one lumen of the catheter, while the other lumen measured distal pressure (Pb). At FRC, the resistance to collateral ventilation (Rcoll) was calculated as Rcoll = Pb/Vcoll. The rest of the lung was ventilated with air, while air (hypocapnia), 10% CO2 in air, or air and halothane or isoflurane were delivered to the isolated segment. A measurement of resistance was made after 4 min of test gas flow. For each segment, when air replaced 10% CO2, the average increase in Rcoll was calculated and called Rmax. When 10% CO2 in air was infused into segments the mean Rcoll (n = 50) was 0.0196 +/- 0.0022 cmH2O X ml-1 X min. This increased to 0.0285 +/- 0.0031 cmH2O X ml-1 X min (mean +/- E) when air was infused, a mean increase in resistance of 52 +/- 3%. When halothane or isoflurane was added to air the hypocapnic increase in Rcoll was attenuated with a 50% decrease at 1.3% (1.4 MAC and 0.8 MAC, respectively). These two inhalational anesthetics reduce active changes in the flow resistance to collateral ventilation. When collateral resistance acts to adjust ventilation perfusion deviations, this action of halothane and isoflurane may make this regulation less effective.     

Isoflurane and nitrous oxide: comparative impact on cerebrospinal fluid pressure in patients with brain tumors.

The relative effects on cerebrospinal fluid pressure (CSFP) of equipotent concentrations of isoflurane and N2O were compared in 20 patients with brain tumors who had lumbar subarachnoid catheters in place. Patients were randomly assigned to receive one of two anesthetic sequences: group 1, 0.7% end-tidal isoflurane in O2, which was changed to 70% N2O in O2; or group 2, 70% N2O in O2, which was changed to 0.7% end-tidal isoflurane in O2. End-tidal PCO2 and percent end-tidal N2O and isoflurane were monitored by mass spectrometry from just before changing anesthetics (time = 0 min) until the end of a 20-min observation period (time = 20 min). Ventilation was held constant at PaCO2 = 36 +/- 1 mm Hg (mean +/- SE). The patients in group 1 sustained an increase in CSFP that reached a maximum of 33% above the value at 0 min, despite a 3-mm Hg decrease in PaCO2 (P < 0.05). By contrast, CSFP remained unchanged in group 2. Although the absolute increase in CSFP after replacement of isoflurane/O2 by N2O/O2 anesthesia was relatively small (9 +/- 1 to 12 +/- 2 mm Hg; P < 0.05), the absence of a similar effect in patients where N2O was replaced by isoflurane suggests that replacement of isoflurane by an equipotent concentration of N2O is more likely to lead to an increase in CSFP in patients with altered intracranial dynamics than is replacement of N2O by isoflurane.     

Haemodynamic and catecholamine responses to calcitonin gene-related peptide during volatile anaesthesia

PURPOSE: Calcitonin gene-related peptide (CGRP) produces vasodilatation, hypotension, and tachycardia. Tachycardia induced by CGRP may be due to sympathetic activation. Volatile anaesthetics attenuate activation of arterial baroreflexes. We examined the haemodynamic and endocrine effects of CGRP infusion (4 micrograms.kg-1) during anaesthesia with either enflurane or isoflurane in dogs. METHODS: Measurements of haemodynamic variables and hormone assays for plasma catecholamines were made before, during, and after CGRP infusion. Anaesthesia consisted of induction with 25 mg.kg-1 pentobarbital, followed by either enflurane (n = 7) or isoflurane (n = 7) to achieve a 1.0 end-tidal minimum alveolar concentration in oxygen 100%. RESULTS: Mean arterial pressure and systemic vascular resistance decreased (P < 0.01) and the reductions in both variables were similar during CGRP infusion in both groups. Cardiac index (CI) was increased (P < 0.01) in the enflurane group throughout the study while CI increased (P < 0.01) only during infusion in the isoflurane group. Heart rate (HR) remained unchanged (from 135 +/- 6 bpm to 134 +/- 7 bpm) in the enflurane group but tended to increase (from 162 +/- 9 bpm to 171 +/- 9 bpm) in the isoflurane group during infusion. Intergroup differences in HR were found (P < 0.05). Plasma epinephrine concentrations increased (from 42.4 +/- 12.7 pg.ml-1 to 115.3 +/- 41.8 pg.ml-1, P < 0.01) during infusion in the isoflurane group. However, these increases were suppressed (from 46.6 +/- 23.2 pg.ml-1 to 64.7 +/- 32.4 pg.ml-1) to a greater extent in the enflurane group. CONCLUSION: The haemodynamic responses, except for HR, of CGRP infusion are similar during enflurane and isoflurane anaesthesia. Suppression of tachycardia induced by CGRP is greater with enflurane than with isoflurane. The differences in HR may be due to the roles of catecholamine responses resulting from the anaesthetic-induced sympathetic suppression.     

Flumazenil improves cognitive and neuromotor emergence and attenuates shivering after halothane-, enflurane- and isoflurane-based anesthesia

PURPOSE: To conduct a randomized, placebo-controlled, double-blinded, clinical experiment testing the hypothesis that flumazenil, a benzodiazepine antagonist, may affect recovery from halothane-, enflurane- and isoflurane-based anesthesia. METHOD: Patients who underwent surgery under N(2)O/O(2) plus halothane (n=100), enflurane (n=100) or isoflurane (n=70) anesthesia were administered flumazenil 1 mg or placebo upon emergence from anesthesia, and their postanesthesia vital signs, vigilance, neurological recovery, shivering, amnesia reversal, and general subjective feeling were assessed. RESULTS: A ten-point vigilance score showed better recovery of flumazenil-treated patients compared to those who received placebo (60-min after halothane anesthesia: 9.9 +/- 0.1 vs 9.5 +/- 0.2, P <0.01; after enflurane: 10 +/- 0 vs 9.4 +/- 0.2, P <0.01; after isoflurane: 10.0 +/- 0 vs 9.3 +/- 0.1, P <0.01). Halothane- and enflurane-flumazenil-treated patients (but not isoflurane) reached a better neurological score (2.97 +/- 0.05 or 3 +/- 0) compared to placebo (2.8 +/- 0.4 or 2.6 +/- 0.4, P <0.01), respectively. Reversal of amnesia was superior in the flumazenil group at 60 min and at 24 hr postsurgery, and more flumazenil patients rated recovery as "pleasant". Flumazenil patients shivered less than placebo patients despite their lower core temperature (at 30 min: halothane: 11% vs 28%, P <0.05; enflurane: 11% vs 30%, P <0.05; isoflurane: 17% for both groups). CONCLUSION: Flumazenil improves recovery of high cortical and neuromotor functions following halothane, enflurane and isoflurane anesthesia, reduces shivering and improves the overall quality of emergence, including patients' subjective feeling.     

Pharmacology of laudanosine in dogs

The authors determined the pharmacokinetics (including transfer into cerebrospinal fluid [CSF]) and the cardiovascular and central nervous system (CNS) effects of laudanosine, a metabolite of atracurium. Eight dogs were anesthetized with halothane; blood pressure and a fronto-occipital electroencephalographic lead were monitored. Laudanosine (1 mg . kg-1 iv) was administered as a bolus, and its concentrations in plasma, CSF, urine, and bile were determined by liquid chromatography. Three-compartment modeling of plasma laudanosine concentrations yielded an elimination half-life for laudanosine of 113 +/- 24 min (mean +/- SD) and a clearance of 25 +/- 8 ml . kg-1 . min-1. CSF concentrations of laudanosine were highest 5-10 min after iv injection of laudanosine and ranged in concentration from 208 to 572 ng . ml-1 (i.e., 36-87% of the corresponding plasma concentrations). Unchanged laudanosine was found in urine (0.5-12% of injected dose) and bile (less than 0.1%); metabolites of laudanosine were found in both fluids. After a 6-h sampling period, dogs were hyperventilated with halothane (FIO2 = 0.2) to a PaCO2 of 26-28 mmHg. Laudanosine was then administered 2 mg . kg-1 iv every 5 min. With cumulative doses of 2-8 mg . kg-1, all dogs showed signs of "awakening" from anesthesia. Cumulative doses of 14-22 mg . kg-1 produced seizure activity in all animals. Mean arterial blood pressure decreased significantly to 86% of control levels at 1 min following administration of laudanosine (1 mg . kg-1 iv) and returned to control levels 4 min later.(ABSTRACT TRUNCATED AT 250 WORDS)