Bradley J. Hindman

A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy : propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide

Background:Different anesthetic agents have different effects on cerebrovascular physiology. However, the importance of these differences In neuroanesthetic practice are unclear. In an effort to determine whether important clinical differences are present, the authors compared three anesthetic techniques in 121 adults undergoing elective surgical removal of a supratentorial, intracranial mass lesion. Methods:Patients were assigned randomly to one of three groups. In group 1 (n=40), anesthesia was induced with propofol and maintained with fentanyl (≊10 µg/kg load, 2-3 µg · kg-1 · h-1 infusion) and propofol (50-300 µg · kg-1 · mln-1). In group 2 (n=40), anesthesia was induced with thiopental and maintained with isoflurane and nitrous oxide. Up to 2 µg/kg fentanyl was given after replacement of the bone flap. In group 3 (n=41), anesthesia was induced with thiopental and maintained with fentanyl (≊10 µg/kg load, 2-3 µg · kg-1 · h1 infusion), nitrous oxide, and low-dose Isoflurane, if required. Blood pressure, heart rate, expired gas concentrations, and ventilatory parameters were recorded automatically in all patients. Epidural intracranial pressure (ICP) was measured via the first burr hole, brain swelling was rated at the time of dural opening, and emergence was monitored closely. Preoperative computed tomography or magnetic resonance imaging scans were evaluated, and pre- and postoperative neurologic exams were performed by a neurosurgeon unaware of group assignments. Total hospital stay (days) and total hospital cost (exclusive of physician charges) also were reviewed. Results:During induction, higher heart rates were seen in isoflurane/nitrous oxide patients, whereas mean arterial pressure was ≊10 mmHg less during the maintenance phase (compared with both other groups). Otherwise, there were few intergroup hemodynamic differences. While there were no clinically important intergroup differences in mean ICP (±SD)—group 1, ICP=12 ± 7 mmHg; group 2,15 ± 12 mmHg; group 3, ICP=11 ± 8 mmHg—more isoflurane/nitrous oxide patients (nine, group 2) had an ICP £24 mmHg than in the other groups (two each). Emergence was, overall, more rapid with fentanyl/nitrous oxide. For example, the median time until the patient could be awakened by quiet verbal command, e.g., “Open your eyes,” was 5 min, versus 10 min in the other groups. There were no relationships between ICP and any measurement of emergence (e.g., time to response to commands). Seven of 41 (17%) fentanyl/nitrous oxide patients vomited In the early postoperative period, compared with only 1 of 40 (2.5%) of those given propofol/fentanyl and 2 of 40 (5%) receiving isoflurane/nitrous oxide (P=0.03). There were no differences in the incidence of new postoperative deficits, total hospital stay, or cost. Conclusions:Although there are modest differences among the three tested anesthetics, short-term outcome was not affected. These results indicate that, despite their respective cerebrovascular effects, all of the anesthetic regimens used were acceptable in these patients undergoing elective surgery.

Mild Hypothermia as a Protective Therapy during Intracranial Aneurysm Surgery: A Randomized Prospective Pilot Trial

OBJECTIVE To conduct a pilot trial of mild intraoperative hypothermia during cerebral aneurysm surgery. METHODS One hundred fourteen patients undergoing cerebral aneurysm clipping with (n = 52) (World Federation of Neurological Surgeons score < or =III) and without (n = 62) acute aneurysmal subarachnoid hemorrhage (SAH) were randomized to normothermic (target esophageal temperature at clip application of 36.5 degrees C) and hypothermic (target temperature of 33.5 degrees C) groups. Neurological status was prospectively evaluated before surgery, 24 and 72 hours postoperatively (National Institutes of Health Stroke Scale), and 3 to 6 months after surgery (Glasgow Outcome Scale). Secondary outcomes included postoperative critical care requirements, respiratory and cardiovascular complications, duration of hospitalization, and discharge disposition. RESULTS Seven hypothermic patients (12%) could not be cooled to within 1 degrees C of target temperature; three of the seven were obese. Patients randomized to the hypothermic group more frequently required intubation and rewarming for the first 2 hours after surgery. Although not achieving statistical significance, patients with SAH randomized to the hypothermic group, when compared with patients in the normothermic group, had the following: 1) a lower frequency of neurological deterioration at 24 and 72 hours after surgery (21 versus 37-41%), 2) a greater frequency of discharge to home (75 versus 57%), and 3) a greater incidence of good long-term outcomes (71 versus 57%). For patients without acute SAH, there were no outcome differences between the temperature groups. There was no suggestion that hypothermia was associated with excess morbidity or mortality. CONCLUSION Mild hypothermia during cerebral aneurysm surgery is feasible in nonobese patients and is well tolerated. Our results indicate that a multicenter trial enrolling 300 to 900 patients with acute aneurysmal SAH will be required to demonstrate a statistically significant benefit with mild intraoperative hypothermia.

Comparison of Remifentanil and Fentanyl in Patients Undergoing Craniotomy for Supratentorial Space-occupying Lesions

BackgroundRemifentanil hydrochloride is an ultra-short-acting, esterase-metabolized micro-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions.MethodsSixty-three adults gave written informed consent for

Intracranial Pressure and Hemodynamic Effects of Remifentanil Versus Alfentanil in Patients Undergoing Supratentorial Craniotomy

Remifentanil hydrochloride is an ultra-short-acting esterase metabolized mu-opioid receptor agonist. The purpose of this study was to provide preliminary information regarding the effects of this drug on intracranial pressure (ICP) and mean arterial pressure (MAP) in patients scheduled for craniotomy. Twenty-six patients undergoing excision of supratentorial space-occupying lesions were anesthetized with 0.3-0.8 vol% isoflurane in a 2:1 mixture of nitrous oxide:oxygen. Ventilation was adjusted to provide a PaCO2 of <30 mm Hg. After the first burr hole was drilled, patients (n = 5-6 per group) were administered an intravenous infusion of study drug (placebo, remifentanil 0.5 micro gram/kg or 1.0 micro gram/kg, or alfentanil 10 micro gram/kg or 20 micro gram/kg) over 1 min. Epidural ICP and MAP values were recorded at baseline, at completion of infusion, and every minute for the next 10 min. Blood study drug concentrations were measured immediately after completion of infusion. Neither opioid caused a significant increase in ICP. Both drugs were associated with a dose-dependent decrease in MAP. Remifentanil was 31 times more potent than alfentanil for effects on MAP. We conclude that remifentanil produces similar cerebral perfusion pressure effects as does alfentanil. (Anesth Analg 1996;83:348-53)

Theoretical analysis of cerebral venous blood hemoglobin oxygen saturation as an index of cerebral oxygenation during hypothermic cardiopulmonary bypass. A counterproposal to the "luxury perfusion" hypothesis.

Background Jugular venous catheters and near-infrared spectroscopy can measure cerebral venous blood hemoglobin oxygen saturation (SvO 2). We used computer simulation to characterize the relation between Sv sub O2 and cerebral metabolic rate for oxygen (CMRO2) during hypothermic cardiopulmonary bypass (CPB).

Rapid rewarming causes an increase in the cerebral metabolic rate for oxygen that is temporarily unmatched by cerebral blood flow : A study during cardiopulmonary bypass in rabbits

Background Jugular venous hemoglobin desaturation during the rewarming phase of cardiopulmonary bypass is associated with adverse neuropsychologic outcome and may indicate a pathologic mismatch between cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). In some studies, rapid rewarming from hypothermic cardiopulmonary bypass results in greater jugular venous hemoglobin desaturation. The authors wished to determine if rewarming rate influences the temperature dependence of CBF and CMRO2. Methods Anesthetized New Zealand white rabbits, cooled to 25 degrees Celsius on cardiopulmonary bypass, were randomized to one of two rewarming groups. In the fast group (n = 9), aortic blood temperature was made normothermic over 25 min. Cerebral blood flow (microspheres) and CMRO2 (Fick) were determined at baseline (25 degrees C), and at brain temperatures of 28 degrees, 31 degrees, 34 degrees, and 37 degrees Celsius during rewarming. Results Systemic physiologic variables appeared similar between groups. At a brain temperature of 28 degrees C, CMRO2 was 47% greater in the fast rewarming group than in the slow group (2.2 +/‐0.5 vs. 1.5+/‐0.2 ml O2 *symbol* 100 g sup ‐1 *symbol* min sup ‐1, respectively; P = 0.01), whereas CBF did not differ (48+/‐18 vs. 49+/‐8 ml *symbol* 100 g sup ‐1 *symbol* min sup ‐1, respectively; P = 0.47). Throughout rewarming, CBF increased as a function of brain temperature but was indistinguishable between groups. Cerebral metabolic rate for oxygen differences between groups decreased as brain temperatures increased. Conclusions Cerebral venous hemoglobin desaturation with rapid rewarming is caused by an increase in CMRO2 that is temporarily greater than the increase in CBF. This mismatch may indicate a transient abnormality in flow‐metabolism coupling, or the effect of temperature gradients on oxygen transfer from hemoglobin to brain.

Manual In-line Stabilization Increases Pressures Applied by the Laryngoscope Blade during Direct Laryngoscopy and Orotracheal Intubation

Background:Manual in-line stabilization (MILS) is recommended during direct laryngoscopy and intubation in patients with known or suspected cervical spine instability. Because MILS impairs glottic visualization, the authors hypothesized that anesthesiologists would apply greater pressure during intubations with MILS than without. Methods:Nine anesthetized and pharmacologically paralyzed patients underwent two sequential laryngoscopies and intubations, one with MILS and one without, in random order. A transducer array along a Macintosh 3 laryngoscope blade continuously measured applied pressures, and glottic view was characterized. Results:With MILS, glottic visualization was worse in six patients, and intubation failure occurred in two of these six patients. Maximum laryngoscope pressure at best glottic view was greater with MILS than without (717 ± 339 mmHg vs. 363 ± 121 mmHg, respectively; n = 8; P = 0.023). Other measures of pressure application also indicated comparable increases with MILS. Conclusion:Pressures applied to airway tissues by the laryngoscope blade are secondarily transmitted to the cervical spine and result in cranio-cervical motion. In the presence of cervical instability, impaired glottic visualization and secondary increases in pressure application with MILS have the potential to increase pathologic cranio-cervical motion.

Recommendations for Hyperbaric Oxygen Therapy of Cerebral Air Embolism Based on a Mathematical Model of Bubble Absorption

Transcranial doppler studies show that microscopic cerebral artery air emboli (CAAE) are present in virtually all patients undergoing cardiac surgery.Massive cerebral arterial air embolism is rare. If it occurs, hyperbaric oxygen therapy (HBO) is recommended as soon as surgery is completed. We used a mathematical model to predict the absorption time of CAAE, assuming that the volumes of clinically relevant CAAE vary from 10-7 to at least 10-1 mL. Absorption times are predicted to be at least 40 h during oxygenation using breathing gas mixtures of fraction of inspired oxygen approximately equal to 40%. When CAAE are large enough to be detected by computerized tomography, absorption times are calculated to be at least 15 h. Decreases in cerebral blood flow caused by the CAAE would make the absorption even slower. Our analysis suggests that if the diagnosis of massive CAAE is suspected, computerized tomography should be performed, and consideration should be given to HBO therapy if the CAAE are large enough to be visualized, even if patient transfer to a HBO facility will require several hours. (Anesth Analg 1997;84:1203-7)

Heparin Reduces Neurological Impairment After Cerebral Arterial Air Embolism in the Rabbit

BACKGROUND AND PURPOSE Neurological injury after cerebral air embolism may be due to thromboinflammatory responses at sites of air-injured endothelium. Because heparin inhibits multiple thromboinflammatory processes, we hypothesized that heparin would decrease neurological impairment after cerebral air embolism. METHODS To first establish a dose of air that would cause unequivocal neurological injury, anesthetized New Zealand White rabbits received either 0, 50, 100, or 150 microL/kg of air into the internal carotid artery (n = 5 in each group). One hour later, anesthesia was discontinued. Animals were neurologically evaluated at 24 hours with the use of a scale ranging from 0 (normal) to 97 (coma) points. In a subsequent experiment, anesthetized rabbits received either heparin (n = 17) or saline (n = 15) 5 minutes before air injection (150 microL/kg). Heparin was given as a 200-IU/kg bolus and followed by a constant infusion of 75 IU.kg-1.h-1 for 2 hours. Equal volumes of saline were given to control rabbits. Two hours later, anesthesia was discontinued. Animals were neurologically evaluated 24 hours after air embolism. RESULTS There was a monotonic relationship between dose of air and severity of neurological impairment at 24 hours (P = 1.1 x 10(-7)). Animals receiving 150 microL/kg of air were unequivocally injured (score, 60 +/- 16). In the second experiment, heparin animals had significantly less neurological impairment at 24 hours (34 +/- 14) than saline controls (52 +/- 8) (P = .0013). CONCLUSIONS When given prophylactically, heparin decreases neurological impairment caused by severe cerebral arterial air embolism.

Cerebral autoregulation during moderate hypothermia in rats.

Background and Purpose Little is known about the effects of hypothermia on cerebral autoregulation. The present study was designed to examine cerebral blood flow responses to controlled hemorrhagic hypotension in normothermic and hypothermic rats. Methods Cortical blood flow was measured with a laser-Doppler flowmeter in halothane-anesthetized rats assigned to one of three groups: normothermic group 1(n=8) with a pericranial temperature of ≈36.5°C or hypothermic group 2 (n=8) or group 3 (n=8) with a pericranial temperature of ≈30.5°C. In group2, a Paco2 of ≈40 mm Hg was maintained without correction for body temperature. To evaluate the role of Paco2, in group 3 animals Paco2, was kept at ≈40 mm Hg as corrected for body temperature. In all animals, the mean arterial blood pressure was reduced by hemorrhage in increments of 10 mm Hg every 2 minutes. Results In group 1 animals, a typical autoregulatory curve was observed with cerebral blood flow first falling at or below 75% of baseline at a mean arterial pressure of 57 ±15 mm Hg (mean±SD). Absolute normotensive cerebral blood flow in group2 fell to ≤75% of baseline at a mean arterial pressure of 73±21 mm Hg. In group3, no evidence of autoregulation was seen. Cerebral blood flow reached values ≤75% of baseline at a mean arterial pressure of 82±14 mm Hg, whereas calculated cerebrovascular resistance failed to show any compensatory vasodilation as the mean arterial pressure decreased. Conclusions Different Paco2 management schemes used during hypothermia may have profound effects on cerebral blood flow and on autoregulation. If Paco2 is maintained at 40 mm Hg after correction for temperature, autoregulation is abolished. If uncorrected Paco2 is maintained at ≈40 mm Hg, some degree of autoregulation is preserved, albeit with a right-shifted “knee.”