The effects of isoflurane and desflurane on intracranial pressure,cerebral perfusion pressure,and cerebral arteriovenous oxygen content difference in normocapnic patients with supratentorial brain tumors

BACKGROUND: Desflurane is a volatile anesthetic agent with low solubility whose use in neurosurgery has been debated because of its effect on intracranial pressure and cerebral blood flow. The purpose of this study was to determine the variations on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) as well as on cerebral arteriovenous oxygen content difference (AVDo(2)) in normocapnic patients scheduled to undergo removal of supratentorial brain tumors with no evidence of mass effect during anesthesia with isoflurane or desflurane. METHODS: In 60 patients scheduled to undergo craniotomy and removal of supratentorial brain tumors with no evidence of midline shift, anesthesia was induced with intravenous fentanyl, thiopental, and vecuronium and was maintained with 60% nitrous oxide in oxygen. Patients were assigned to two groups randomized to receive 1 minimum alveolar concentration isoflurane or desflurane for 30 min. Heart rate, mean arterial pressure, intraparenchymal ICP, and CPP were monitored continuously. Before and after 30 min of continuous administration of the inhaled agents, AVDo(2) was calculated. RESULTS: There were no significant differences between groups in heart rate, mean arterial pressure, ICP, and CPP. ICP measurements throughout the study did not change within each group compared to baseline values. Mean arterial pressure decreased significantly in all patients compared to baseline values, changing from 105 +/- 14 mmHg (mean +/- SD) to 85 +/- 10 mmHg in the isoflurane group and from 107 +/- 11 mmHg to 86 +/- 10 mmHg in the desflurane group (P < 0.05 in both groups). CPP also decreased within each group compared with baseline values, changing from 95 +/- 15 mmHg to 74 +/- 11 mmHg in the isoflurane group and from 95 +/- 16 mmHg to 74 +/- 10 mmHg in the desflurane group (P < 0.05 in both groups). Cerebral AVDo(2) decreased significantly in both groups throughout the study, changing from 2.35 +/- 0.77 mm to 1.82 +/- 0.61 mm (mmol/l) in the isoflurane group (P < 0.05) and from 2.23 +/- 0.72 mm to 1.94 +/- 0.76 mm in the desflurane group (P < 0.05), without differences between groups. CONCLUSIONS: The results of this study indicate that there are no variations on ICP in normocapnic patients undergoing removal of supratentorial brain tumors without midline shift, as they were anesthetized with isoflurane or desflurane. CPP and cerebral AVDo(2) decreased with both agents.     

Blood pressure response to thermoregulatory vasoconstriction during isoflurane and desflurane anesthesia

BACKGROUND: Mild perioperative hypothermia produces morbid cardiac outcomes that may result from sympathetically induced hypertension. However, volatile anesthetics produce vasodilatation that may reduce the hemodynamic response to hypothermia. We tested the hypothesis that the volatile anesthetics isoflurane and desflurane blunt the normal cold-induced hypertensive response. METHODS: We analyzed prospective data from three analogous studies: 1) 10 volunteers given desflurane (2.6 volume percentage) maintained in left-lateral position; 2) nine volunteers without anesthesia or anesthetized with various doses of desflurane; and 3) eight volunteers given various concentrations of isoflurane. Mean skin temperature was reduced to 31 C, which decreased core body temperature and triggered thermoregulatory vasoconstriction. Mean arterial pressures were determined before and after hypothermia provoked intense thermoregulatory vasoconstriction. RESULTS: The hemodynamic responses to thermoregulatory vasoconstriction were similar without anesthesia and at all concentrations of desflurane and isoflurane. On average, mean arterial pressure increased 14 (SD = 5) mmHg with and without anesthesia. CONCLUSION: We conclude that thermoregulatory vasoconstriction significantly increases arterial pressure with or without isoflurane or desflurane anesthesia.     

The Effects of Isoflurane and Desflurane on Intracranial Pressure, Cerebral Perfusion Pressure, and Cerebral Arteriovenous Oxygen Content Difference in Normocapnic Patients with Supratentorial Brain Tumors

Background: Desflurane is a volatile anesthetic agent with low solubility whose use in neurosurgery has been debated because of its effect on intracranial pressure and cerebral blood flow. The purpose of this study was to determine the variations on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) as well as on cerebral arteriovenous oxygen content difference (AVDo2) in normocapnic patients scheduled to undergo removal of supratentorial brain tumors with no evidence of mass effect during anesthesia with isoflurane or desflurane.

Methods: In 60 patients scheduled to undergo craniotomy and removal of supratentorial brain tumors with no evidence of midline shift, anesthesia was induced with intravenous fentanyl, thiopental, and vecuronium and was maintained with 60% nitrous oxide in oxygen. Patients were assigned to two groups randomized to receive 1 minimum alveolar concentration isoflurane or desflurane for 30 min. Heart rate, mean arterial pressure, intraparenchymal ICP, and CPP were monitored continuously. Before and after 30 min of continuous administration of the inhaled agents, AVDo2 was calculated.

Results: There were no significant differences between groups in heart rate, mean arterial pressure, ICP, and CPP. ICP measurements throughout the study did not change within each group compared to baseline values. Mean arterial pressure decreased significantly in all patients compared to baseline values, changing from 105 +/- 14 mmHg (mean +/- SD) to 85 +/- 10 mmHg in the isoflurane group and from 107 +/- 11 mmHg to 86 +/- 10 mmHg in the desflurane group (P < 0.05 in both groups). CPP also decreased within each group compared with baseline values, changing from 95 +/- 15 mmHg to 74 +/- 11 mmHg in the isoflurane group and from 95 +/- 16 mmHg to 74 +/- 10 mmHg in the desflurane group (P < 0.05 in both groups). Cerebral AVDo2 decreased significantly in both groups throughout the study, changing from 2.35 +/- 0.77 mm to 1.82 +/- 0.61 mm (mmol/l) in the isoflurane group (P < 0.05) and from 2.23 +/- 0.72 mm to 1.94 +/- 0.76 mm in the desflurane group (P < 0.05), without differences between groups.     

The effect of desflurane and isoflurane on cerebrospinal fluid pressure in humans with supratentorial mass lesions.

Desflurane, a new volatile anesthetic, produces cerebral vasodilation. The purpose of this study was to compare the effects of 1 MAC desflurane with those of isoflurane on cerebrospinal fluid pressure (CSFP) in patients with supratentorial mass lesions and a mass effect on computerized tomography (CT scan). Twenty adult patients undergoing craniotomy for removal of supratentorial mass lesions were studied. Ten patients received desflurane and 10 patients received isoflurane. Prior to induction of anesthesia, a radial artery catheter was inserted and a 19-G needle was inserted into the lumbar subarachnoid space to measure CSFP. Baseline arterial blood gases and CSFP were measured with the patient awake and unmedicated. Anesthesia was induced with thiopental (6-9 mg/kg) and muscle relaxation achieved with vecuronium (0.2 mg/kg). The lungs of all patients were hyperventilated to achieve an arterial CO2 tension of 24-28 mmHg. Anesthesia was maintained with 1 MAC volatile anesthetic, either 7.0% desflurane or 1.2% isoflurane in an air:O2 mixture to maintain an inspired O2 fraction (FIO2) of 0.50. Patients were not administered any other anesthetic until the dura was incised. Mean arterial pressure was kept within 20% of the patient's mean ward values with the use of esmolol or phenylephrine. CSFP, mean arterial pressure, end-tidal CO2 concentration (PETCO2), hemoglobin O2 saturation, and cerebral perfusion pressure were recorded with the patient awake, immediately postinduction with thiopental, postintubation, after institution of the volatile anesthetic, and every 5 min until the dura was incised. There was no difference in the mean (+/- SD) awake CSFP between the desflurane (11 +/- 4 mmHg) and the isoflurane (10 +/- 2 mmHg) groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fentanyl Augments the Blockade of the Sympathetic Response to Incision (MAC-BAR) Produced by Desflurane and Isoflurane: Desflurane and Isoflurane MAC-BAR without and with Fentanyl

Background: Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner.

Methods: Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 micro gram/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group.

Results: Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P > 0.05) and decreased MAP (P < 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P > 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 micro gram/kg intravenously equivalently (P > 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P <0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P < 0.05), but a further increase in fentanyl to 3 micro gram/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC).     

Hemodynamic changes during fentanyl--oxygen anesthesia for aortocoronary bypass operation

Fentanyl in doses of 50-60 microgram/kg has been reported to produce anesthesia with remarkable hemodynamic stability in patients with coronary artery disease (CAD). Because the authors had observed hypertension and tachycardia in response to noxious stimulation during aortocoronary bypass (ACB) operations in patients so anesthetized, they studied the hemodynamic changes and anesthetic conditions produced by fentanyl/O2/relaxant anesthesia in patients undergoing elective ACB. Twelve patients with left ventricular (LV) ejection fractions greater than 0.4 were maintained on propranolol until 10 hours before operation and were premedicated with fentanyl, diazepam, and scopolamine. Cannulae were inserted before the study commenced for measurement of intravascular pressures, arterial blood gases, and thermodilution cardiac output. The patients breathed 100 per cent oxygen throughout the study. Controlled ventilation aided by succinylcholine to reduce truncal rigidity maintained PaCO2 at 30-45 torr. Measurements were made after each of the following: breathing oxygen (control), 10 microgram/kg fentanyl, 50 microgram/kg fentanyl, and 0.1 mg/kg pancuronium, tracheal intubation, skin incision, and sternotomy. Fentanyl alone produced no significant hemodynamic changes. Fentanyl and pancuronium in combination produced increased heart rate and reduced stroke volume. Significant and progressively greater increases in mean arterial pressure and systemic vascular resistance followed intubation, skin incision, and sternotomy. Chest rigidity occurred in every patient at a lower fentanyl dose than did unresponsiveness. While fentanyl, 62.4 +/- 2.9 microgram/kg (SE), produced minor hemodynamic changes, it failed to block hemodynamic responses to noxious stimulation. Such changes resulted in increased cardiac work, and could have affected myocardial oxygen balance unfavorably. In eight of the 12 patients, following the last set of measurements, supplementary anesthetic agents were required to maintain hemodynamic stability during the surgical procedure. The authors suggest that this fentanyl/O2/relaxant technique should be modified for patients with severe CAD and reasonably good LV function.     

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.     

Complete myocardial revascularization on the beating heart with epicardial stabilization: anesthetic considerations

OBJECTIVE: To describe an anesthetic management protocol for patients undergoing cardiac surgery with multiple coronary artery bypass grafts without cardiopulmonary bypass (off-pump CABG surgery) by median sternotomy with mechanical stabilization. DESIGN: Retrospective nonrandomized analysis. SETTING: Tertiary care hospital. PARTICIPANTS: Sixty-six consecutive patients on whom off-pump CABG surgery by median sternotomy was attempted. INTERVENTIONS: Anesthesia was induced with a combination of etomidate and fentanyl; pancuronium bromide was given for muscle relaxation; and anesthesia was maintained with isoflurane, desflurane, or sevoflurane in 100% oxygen. Maintenance of normothermia was attempted by keeping the room temperature at 70 degrees F, warming all fluids to 41 degrees C, and using 2.5 L/min of fresh gas flows and a heat and humidity exchanger. When available, a convective forced-air blanket was used to cover patients' head and shoulders. Patients who were not slated for revascularization of the circumflex vessels and who had good ventricular function received central venous pressure monitoring (26%); all other patients received a pulmonary artery catheter. MEASUREMENTS AND MAIN RESULTS: Of the 66 patients, 36% required an epinephrine infusion at a mean rate of 1.45+/-2.05 microg/min intraoperatively to maintain hemodynamic stability; 25% required inotropic support for < 12 hours in the intensive care unit. CONCLUSION: Institution of systematic hemodynamic management was associated with the successful completion of the surgical procedure in 61 patients (92%). Only 5 patients required conversion to regular CABG surgery with cardiopulmonary bypass.     

Comparison of the systemic and coronary hemodynamic actions of desflurane, isoflurane, halothane, and enflurane in the chronically instrumented dog

The systemic and coronary hemodynamic effects of desflurane were compared to those of isoflurane, halothane, and enflurane in chronically instrumented dogs. Since autonomic nervous system function may significantly influence the hemodynamic actions of anesthetics in vivo, a series of experiments also was performed in the presence of pharmacologic blockade of the autonomic nervous system. Eight groups comprising a total of 80 experiments were performed on 10 dogs instrumented for measurement of aortic and left ventricular pressure, the peak rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, coronary blood flow velocity, and cardiac output. Systemic and coronary hemodynamics were recorded in the conscious state and after 30 min equilibration at 1.25 and 1.75 MAC desflurane, isoflurane, halothane, and enflurane. Desflurane (+79 +/- 12% change from control) produced greater increases in heart rate than did halothane (+44 +/- 12% change from control) or enflurane (+44 +/- 9% change from control) at 1.75 MAC. Desflurane preserved mean arterial pressure to a greater degree than did equianesthetic concentrations of isoflurane. This result was attributed to a smaller effect on peripheral vascular resistance as compared to isoflurane and greater preservation of myocardial contractility as evaluated by peak positive left ventricular dP/dt and the rate of increase of ventricular pressure at 50 mmHg (dP/dt50) compared to other volatile anesthetics. Increases in diastolic coronary blood flow velocity (+19 +/- 6 and +35 +/- 12% change from control at 1.75 MAC, respectively) and concomitant decreases in diastolic coronary vascular resistance (-41 +/- 12 and -58 +/- 6% change from control at 1.75 MAC, respectively) were produced by desflurane and isoflurane. In the presence of autonomic nervous system blockade, the actions of desflurane and isoflurane were nearly identical with the exception of coronary vasodilation. After autonomic nervous system blockade, isoflurane increased coronary blood flow velocity, but desflurane did not. Furthermore, both desflurane and isoflurane continued to produce less depression of myocardial contractility than did halothane and enflurane. In summary, at equianesthetic concentrations, desflurane and isoflurane produced similar hemodynamic effects; however, in the absence of drugs that inhibit autonomic reflexes, desflurane had less negative inotropic activity and produced less decrease in arterial pressure. The coronary vasodilator actions of desflurane and isoflurane within the limitations of this model were not similar. When the increase in heart rate and rate-pressure product produced by desflurane were prevented in dogs with autonomic nervous system blockade, desflurane produced no change in coronary blood flow velocity.     

Hepatocellular integrity in swine after prolonged desflurane (I-653) and isoflurane anesthesia: evaluation of plasma alanine aminotransferase activity

Desflurane, formerly known as I-653 (CF2H-O-CFH-CF3), is a new inhalation anesthetic derived by fluorine substitution for the alpha-ethyl chlorine of isoflurane (CF2H-O-CClH-CF3). The lower solubility and increased stability of desflurane provided by the C-F bond lessen biotransformation to potentially hepatotoxic metabolites. Repeated administration of desflurane to rats, with or without induced hepatic enzymes, does not result in evidence of hepatic injury. In the recent study we extended the tests for liver cell injury to another species, the pig. Our test included prolonged exposure to desflurane or isoflurane, both in the absence and presence of commonly used adjuvants. We measured plasma alanine aminotransferase activity in eight young female swine anesthetized in random order with desflurane (0.8-1.6 MAC) and isoflurane (0.7-1.4 MAC), for a total dose of about 5.5 MAC-hours of each anesthetic, 3-8 days apart. Plasma alanine aminotransferase activities remained in the normal range, and were not significantly greater over baseline values in samples drawn immediately after, 4 h after, or 3-8 days after (mean +/- SD, 6.1 +/- 2.1) the administration of either anesthetic was discontinued after the first study with either desflurane or isoflurane. Five additional pigs were given a mean total dose of 9.7 MAC-hours of desflurane or isoflurane in conjunction with succinylcholine, N2O, fentanyl, naloxone, atracurium, thiopental, edrophonium, and atropine. No changes in plasma alanine aminotransferase activity were detected in blood samples drawn at termination of the anesthesia, 24 h later, and 4-7 days later (mean +/- SD, 5.8 +/- 1.3).(ABSTRACT TRUNCATED AT 250 WORDS)     

The risk of myocardial ischemia in patients receiving desflurane versus sufentanil anesthesia for coronary artery bypass graft surgery. The S.P.I. Research Group.

Desflurane, a coronary vasodilator, may induce myocardial ischemia in patients with coronary artery disease. To determine whether desflurane is safe to administer to the at-risk patient population (with known coronary artery disease), we compared the incidence and characteristics of perioperative myocardial ischemia in 200 patients undergoing coronary artery bypass graft (CABG) surgery randomly assigned to receive desflurane (thiopental adjuvant) versus sufentanil anesthesia. Under conditions of hemodynamic control, perioperative ischemia was assessed using continuous echocardiography (precordial: during induction; transesophageal: during surgery) and Holter electrocardiography (ECG); hemodynamics (including pulmonary artery pressure) were measured continuously. Hemodynamic results: During induction, no significant changes in hemodynamics occurred in the sufentanil group, while in the desflurane group, heart rate, systemic and pulmonary arterial pressure increased and stroke volume decreased significantly. During the intraoperative period, the incidence of hemodynamic variations was low in both anesthetic groups; however, the prebypass incidence of tachycardia (greater than 120% of preoperative baseline heart rate) was greater in the desflurane group (4 +/- 7% of total time monitored) than in the sufentanil group (1 +/- 6%) (P = 0.0003). Similarly, the incidence of prebypass hypotension (less than 80% of preoperative baseline systolic arterial blood pressure) was greater in the desflurane group (21 +/- 14%) than in the sufentanil group (15 +/- 16%) (P = 0.01). ECG results: Preoperatively, 15% (28/191) of patients developed ECG ischemia, with no difference between patients who received desflurane, 13% (12/96) or sufentanil, 16% (16/95) (P = 0.6). During anesthetic induction, 9% (9/99) of patients who received desflurane developed ECG ischemia, compared with 0% (0/98) who received sufentanil (P = 0.007). During the prebypass period, 5% (10/197) of patients developed ECG ischemia, with no difference between patients who received desflurane, 7% (7/99) or sufentanil, 3% (3/98) (P = 0.3). Postbypass, 12% (24/194) of patients developed ECG ischemic changes, with no difference between patients who received desflurane, 13% (13/97) or sufentanil, 11% (11/96) (P = 0.9). Echocardiographic results: The incidence of precordial echocardiographic ischemia during anesthetic induction was 13% (5/39) in the desflurane group versus 0% (0/29) in the sufentanil group (P = 0.1). Moderate to severe transesophageal echocardiographic (TEE) ischemic episodes occurred in 12% (21/175) of patients during prebypass, with no significant difference between the desflurane group, 16% (15/91) and the sufentanil group, 7% (6/84) (P = 0.09). TEE ischemic episodes occurred in 27% (49/178) of patients during the postbypass period, with no difference between the desflurane, 29% (27/92) and sufentanil, 25% (22/86) groups (P = 0.7).(ABSTRACT TRUNCATED AT 400 WORDS)     

Desflurane confers neurologic protection for deep hypothermic circulatory arrest in newborn pigs

BACKGROUND: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), as used for infant heart surgery, carry a risk of ischemic neurologic injury. Volatile anesthetics have neuroprotective properties against both global and focal ischemia at normothermia. The authors examined the hemodynamic and neuroprotective effects of desflurane in a piglet CPB-DHCA model. METHODS: Twenty piglets aged 5-10 days received a desflurane- (6-9% expired) or fentanyl-based anesthetic before and during CPB (before and after DHCA). DHCA lasted 90 min at 19 degrees C brain. Cardiovascular variables (heart rate, arterial pressure, blood gases, glucose, brain temperature) were monitored. On postoperative day 2, neurologic and histologic outcomes were determined. RESULTS: Cardiovascular variables before, during, and after CPB were physiologically similar between groups. The desflurane group had better neurologic performance (P = 0.023) and greater postoperative weight gain (P = 0.04) than the fentanyl group. In neocortex, the desflurane group had less tissue damage (P = 0.0015) and fewer dead neurons (P = 0.0015) than the fentanyl group. Hippocampal tissue damage was less in the desflurane group (P = 0.05), but overall, neuronal cell counts in the CA1 sector of the right hippocampus were similar to those in the fentanyl group. CONCLUSIONS: Desflurane-based anesthesia yields hemodynamics during CPB with DHCA that are similar to those with fentanyl-based anesthesia. However, desflurane-based anesthesia improves neurologic and histologic outcomes of CPB-DHCA in comparison with outcomes with fentanyl-based anesthesia.     

The Influence of Isoflurane on Blood Flow in Coronary Bypass Grafts

The effects of isoflurane on graft blood flow, central hemodynamics and ECG were evaluated in 20 patients during coronary artery surgery in the period immediately after cardiopulmonary bypass (CPB). Intravenous anesthesia with thiopentone, diazepam, fentanyl (continuous infusion), droperidol and pancuronium supplemented with nitrous oxide was used before, and thiopentone and fentanyl were used during CPB. A first measurement of graft flow was performed during fentanyl infusion and the patients were randomly allocated to a control (n = 10) and a study (n = 10) group. In the study group isoflurane was administered in a dose that reduced systolic arterial blood pressure (SAP) to approximately 100 mmHg (13.3 kPa) (inspired concentration 0.5-1.5%) and a second measurement was performed after 30 min. In the control group the infusion of fentanyl was continued. Isoflurane reduced graft blood flow from 52 +/- 5 (mean and s.e. mean) to 40 +/- 5 ml . min-1 (P less than 0.01) concomitant with reductions in SAP, cardiac index, stroke index, left ventricular stroke work index and power index, while these parameters as well as graft flow remained unchanged in the control group. Isoflurane did not produce any change in the degree of ischemia as judged from the ECG. A high blood flow in recently established coronary artery bypass grafts is essential for the prevention of early graft occlusion; therefore the graft-flow-reducing effect of isoflurane has to be taken into consideration when evaluating different anesthetic regimens in the period after CPB.     

Comparison of propofol and isoflurane anesthesia in orthotopic pig-to-baboon cardiac xenotransplantation

BACKGROUND: Orthotopic pig-to-baboon xenogeneic heart transplantation (oXHTx) is the only accepted preclinical animal model for cardiac xenotransplantation. We compared the hemodynamic stability of a propofol- and isoflurane-based anesthetic regimen during oXHTx. METHODS: Hearts from 12 hDAF or hCD46 transgenic pigs (Sus scrofa; body weight 7 to 32 kg) were transplanted into baboons (Papio anubis and Papio hamadryas; body weight 9 to 26 kg) in the orthotopic life-supporting position. Animals received a propofol-based intravenous regimen or inhalation anesthesia with isoflurane. Analgesia was achieved with fentanyl in both groups. Systemic hemodynamic variables were measured before, during and after cardiopulmonary bypass (CPB) and the need for inotropic or vasoactive pharmacological support was compared before and after CPB. RESULTS: Global hemodynamic variables [i.e. heart rate, mean arterial pressure (MAP) and cardiac output] were not significantly different in propofol-anesthetized baboons compared to baboons anesthetized with isoflurane. Baboons anesthetized with isoflurane showed a trend towards less pharmacological support required to achieve an adequate MAP of >60 mmHg after CPB (propofol: epinephrine 0.13 [0.05; 0.16] and norepinephrine 0.15 [0.02; 0.16] microg/kg/min vs. isoflurane: epinephrine 0.05 [0.02; 0.08] and norepinephrine 0.06 [0.02; 0.19] microg/kg/min; no significant difference). CONCLUSIONS: Propofol and isoflurane appear to provide equal hemodynamic stability in orthotopic cardiac pig-to-baboon xenotransplantation prior to the start of CPB. The trend of a reduced catecholamine support needed after CPB, however, suggests that isoflurane may be the preferred drug for maintenance of anesthesia in this primate model.     

Immediate anesthesia recovery and psychomotor function of patient after prolonged anesthesia with desflurane, sevoflurane or isoflurane

OBJECTIVE: To compare the anesthetic maintenance and early postoperative recovery and psychomotor function in patients who have been anesthestized with desflurane, sevoflurane or isoflurane during prolonged open urological surgery. PATIENTS AND METHODS: Seventy-five patients were randomly assigned to receive desflurane, sevoflurane or isoflurane with N2O 60% for anesthetic maintenance. The concentration of each drug was adjusted to maintain arterial pressure and heart rate +/- 20% of baseline. After the operation the anesthetics were discontinued and times until eye opening, spontaneous breathing, extubation and orientation were recorded. In the post-anesthesia recovery ward we applied the Newman-Trieger and Aldrete tests and recorded instances of nausea and vomiting and need for analgesia during the first 24 hours after surgery. RESULTS: The groups were similar with regard to demographic features, anesthetic maintenance, duration of anesthesia and relative doses of the anesthetics used. Recovery times in the operating room were significantly shorter (p < 0.05) after anesthesia with desflurane and sevoflurane than with isoflurane, with no significant differences between the desflurane and sevoflurane groups (duration of anesthesia 198 +/- 90, 171 +/- 67 and 191 +/- 79; eye opening 7.6 +/- 3.7, 7.8 +/- 3.0 and 11.9 +/- 4.5; time until extubation 7.8 +/- 3.0, 8.3 +/- 3.0 and 11.0 +/- 3.5 for desflurane, sevoflurane and isoflurane, respectively; all data in minutes). Recovery in the post-anesthetic recovery ward was similar for all three groups. CONCLUSIONS: Anesthetic maintenance was comparable with all three drugs. Desflurane and sevoflurane demonstrated advantages over isoflurane during recovery from anesthesia in the operating theater. No significant differences were found in psychomotor recovery, nausea and/or vomiting or requirements for postoperative analgesia.     

Desflurane and isoflurane in surgical patients: comparison of emergence time

In order to examine the clinical potential of desflurane (difluoromethyl-1-fluoro-2,2,2-trifluoroethyl ether) in humans, a randomized, controlled study was designed to compare time of emergence from anesthesia in patients undergoing elective surgery under desflurane anesthesia to that of patients under isoflurane anesthesia. Twenty-eight patients were randomly divided into four groups. Group 1 received isoflurane 0.65 MAC; group 2, desflurane 0.65 MAC; group 3, isoflurane 1.25 MAC; and group 4, desflurane 1.25 MAC. Anesthesia was induced with sodium thiopental, and N2O 60% was added to the volatile agent. Mean anesthetic exposure times (min [mean +/- SD]) were 108 +/- 49 in group 1, 132 +/- 46 in group 2, 147 +/- 74 in group 3, and 166 +/- 71 in group 4, with no significant differences between groups. The times from discontinuation of anesthetic gases until patients opened their eyes and squeezed the investigator's hand in response to a command were averaged and recorded as "emergence time." Emergence time was significantly less with desflurane than with isoflurane given at the same MAC. Patients receiving isoflurane 0.65 MAC responded to commands 15.6 +/- 4.3 min after discontinuation of the anesthetic; patients in the desflurane 0.65 MAC group responded in 8.8 +/- 2.7 min (P less than 0.01). Emergence time for isoflurane 1.25 MAC was 30.0 +/- 11.0 min; for desflurane 1.25 MAC it was 16.1 +/- 6.0 min (P less than 0.05). Our results confirm that emergence from desflurane anesthesia is more rapid than from isoflurane.     

The neuromuscular effects of desflurane, alone and combined with pancuronium or succinylcholine in humans

The neuromuscular effects of desflurane administered alone were studied in ten healthy human volunteers aged 20-27 yr. Also, the dose-response relationships of pancuronium and succinylcholine in surgical patients during anesthesia with desflurane (n = 13) were compared to those during isoflurane anesthesia (n = 14). In the volunteers, we measured the mechanical response of the adductor pollicis muscle to stimulation of the ulnar nerve in a train-of-four (TOF) sequence at 2 Hz and at tetanic frequencies of 50, 100, and 200 Hz, each administered for 5 s. Amplitudes of the first response (T1) in each TOF sequence and the ratios of the fourth TOF response (T4) to the first were similar at 3, 6, and 9% desflurane and decreased significantly only at 12% (P less than 0.05). Desflurane concentrations of 3-12% caused tetanic fade (greater than 10% decrement in amplitude) at 50, 100, and 200 Hz. The addition of N2O and the duration of anesthetic exposure did not alter desflurane's neuromuscular effects. The only neuromuscular variable influenced by CO2 was T1 amplitude, which decreased as arterial CO2 tension (PaCO2) increased. The doses of pancuronium that depressed T1 amplitude by 50% (ED50) were similar during anesthesia with 1.25 MAC desflurane, 10.5 +/- 2.8 micrograms/kg (mean +/- SD) and 1.25 MAC isoflurane, 12.3 +/- 5.0 micrograms/kg. The ED50 doses of succinylcholine were similar during anesthesia with desflurane 132 +/- 76 micrograms/kg and isoflurane 123 +/- 36 micrograms/kg. We conclude that desflurane significantly depresses neuromuscular function and augments the action of pancuronium and succinylcholine to a degree similar to that of isoflurane.     

Cardiovascular actions of common anesthetic adjuvants during desflurane (I-653) and isoflurane anesthesia in swine

To determine the cardiovascular actions of drugs commonly combined with inhalation anesthetics, we administered one drug from each of several classes of adjuvants to seven swine already anesthetized with equipotent concentrations (1.2 MAC) of desflurane, formerly I-653, a new inhaled anesthetic, or isoflurane. Succinylcholine (1 and 2 mg/kg), atracurium (0.6 mg/kg), and atropine (5 micrograms/kg) plus edrophonium (5 mg/kg) had no cardiovascular effects. Fentanyl was given in amounts that decreased MAC for the inhaled anesthetics by 25%-35%. A dose of 50 micrograms/kg IV had no cardiovascular effects during either anesthetic, whereas 100 micrograms/kg IV modestly increased systemic vascular resistance without changing other variables. Naloxone (100 micrograms/kg IV) during infusion of fentanyl decreased systemic vascular resistance and increased cardiac output during both desflurane and isoflurane anesthesia, increased heart rate during only isoflurane anesthesia, and did not affect mean arterial blood pressure during either anesthetic. Thiopental (2.5 and 5.0 mg/kg IV) decreased mean aortic blood pressure, cardiac output, stroke volume, and systemic vascular resistance during both anesthetics without altering heart rate or left- or right-sided cardiac filling pressures. The addition of 60% nitrous oxide caused no cardiovascular changes during desflurane anesthesia, but increased systemic vascular resistance and decreased cardiac output and stroke volume during isoflurane without altering heart rate or cardiac preload. We conclude that the usual clinical doses of adjuvants commonly administered during anesthesia have no untoward cardiovascular actions during 1.2 MAC desflurane or isoflurane anesthesia in swine.     

Visceral losses of desflurane, isoflurane, and halothane in swine.

Percutaneous loss of inhaled anesthetics is small relative to their uptake. The minor nature of this loss results in part from the substantial barrier to diffusion posed by the skin. Pleural and peritoneal surfaces pose less effective barriers because diffusion distances are smaller than in the skin. Accordingly, we measured visceral loss to air of desflurane, isoflurane, and halothane from pleural and peritoneal surfaces in five juvenile swine. Pleural and peritoneal losses per percent end-tidal anesthetic correlated directly with the solubility of the anesthetic in blood or tissues. The total pleural losses for the first 30 min of anesthetic administration were desflurane, 1.22 +/- 0.22 mL (mean +/- standard deviation for the 30-min period); isoflurane, 2.34 +/- 0.52 mL; and halothane, 4.69 +/- 0.98 mL; respective peritoneal losses were 0.64 +/- 0.12 mL, 1.23 +/- 0.25 mL, and 2.69 +/- 0.57 mL. Pleural loss per unit time did not change with increasing duration of anesthesia, whereas peritoneal loss increased for all anesthetics. These visceral losses are greater than total percutaneous losses in humans given these anesthetics for the same period of time, but the loss of anesthetic by either route is too small to affect measurements of anesthetic kinetics or recovery.     

Cerebral blood flow autoregulation is preserved during cardiopulmonary bypass in isoflurane-anesthetized patients

In 21 patients undergoing elective coronary artery bypass surgery, cerebral blood flow (CBF) was measured during hypothermic nonpulsatile cardiopulmonary bypass to test the hypothesis that isoflurane abolished the mean arterial pressure-CBF relation (pressure-flow autoregulation). Cerebral blood flow was determined by 133Xe clearance. The patients were randomly divided into three groups according to anesthesia during cardiopulmonary bypass: group 1 received midazolam and fentanyl; group 2 received, in addition to midazolam and fentanyl, 0.6% isoflurane; and group 3 received, in addition to midazolam and fentanyl, 1.2% isoflurane. The groups were maintained at a constant temperature, PaO2, PaCO2, and pump flow during CBF measurements. Mean arterial pressure was increased by phenylephrine greater than or equal to 25% after the first CBF determination. Isoflurane decreased mean arterial pressure significantly (P less than 0.05) and was associated with lower CBF. Increasing the mean arterial pressure 29% in group 1, 25% in group 2, and 34% in group 3 had no effect on CBF. We conclude that, within the range studied, pressure-flow CBF autoregulation is preserved during isoflurane anesthesia administered for cardiopulmonary bypass.