Michael M. Todd

A Comparison of the Cerebrovascular and Metabolic Effects of Halothane and Isolflurane in the Cat

Halothane is a well known cerebral vasodilator that can produce dangerous increases in intracranial pressure (ICP) in certain neurosurgical patients. It has been suggested that isoflurane may be a less potent cerebral vasodilator. The authors therefore undertook a direct comparison of the effects of halothane and isoflurane on cerebral blood flow (CBF), cerebral vascular resistance (CVR), intracranial pressure, and cerebral metabolic rate for oxygen (CMRO2). Studies were carried out in normocarbic mechanically ventilated cats, using the intracarotid 133Xe injection technique to measure CBF. The effects of three doses were examined: 0.5, 1.0, and 1.5 MAC, studied in the continued presence of 75% N2O. Autoregulation also was tested at 1.0 MAC (plus 75% N2O) by recording CBF and CVR before and after elevation of blood pressure with angiotensin.Both agentes had similar effects on blood pressure and ICP. However, while halothane produced significant increases in CBF at all doses, with values of 61 ± 5 ml · 100 g-1 · min-1 (123 ± 8% of control, mean ± SE) at 1.0 MAC, isoflurane anesthesia caused no significant changes in CBF at any level, (e.g., 48 ± 8 ml · 100 g-1 · min-1 or 94 ± 12% of control at 1.0 MAC). Both drugs produced dose-related decreases in CVR, but the changes were greater with halothane, e.g., CVR at 1.0 MAC halothane = 1.46 ± 0.20 mmHg · ml-1 · 100 g · min (47 ± 7% of control) compared with 2.23 ± 0.40 mmHg · ml-1 · 100 g · min (72 ± 9% of control). In addition, isoflurane produced greater decreases in CMRO2 than did halothane, and also impaired autoregulation less.The results indicate that isoflurane possesses cerebrovascular properties that are different from halothane. These differences suggest that isoflurane may come to play an important role in future neuroanesthetic practice.

The effect of high dose sodium thiopental on brain stem auditory and median nerve somatosensory evoked responses in humans.

Median nerve somatosensory evoked potentials (MnSSEPs), brain stem auditory evoked responses (BAERs), and the cortical electroencephalogram (EEG) were recorded in six patients during a 62·min infusion of sodium thiopental (STP) at a rate of 1.25 mg·kg−1·min−1 (total dose, 77.5 mg/kg). The EEG became isoelectric after 22 ± 8 (SD) min of STP infusion. Dose-related changes in the latencies and amplitudes of various evoked response wave forms were observed. However, in no instance was any component of either the MnSSEP or the BAER rendered unobtainable by STP administration. For the MnSSEP, progressive increases in the central conduction time (5.33 ± 0.41 ms preinduction vs. 7.46 ± 1.2 ms at t = 60 min) and in the latency of the cortical primary specific complex were observed simultaneously with significant reductions in the amplitude of the latter (2.10 ± 0.85 μV preinduction vs. 0.85 ± 0.55 μV at t = 60 min). Changes in the latency and amplitude of the response recorded over the upper cervical spine (C2) were not statistically significant in this small population. For the BAER, progressive and significant increases in the latencies of Waves I, III, V (e.g., Wave V latency: 6.16 ± 0.24 vs. 6.87 ± 0.31 ms) and in the I-III, III-V, and the I-V interwave latencies were observed. The amplitudes of the BAER components were not significantly altered. The authors conclude that the administration of a dose of STP in excess of twice that required to produce EEG isoelectricity can be compatible with effective monitoring of MnSSEPs and BAERs. However, STP produces dose-related changes in both evoked response wave forms, which must be considered in the interpretation of responses elicited during STP anesthesia.

The Acute Cerebral Effects of Changes in Plasma Osmolality and Oncotic Pressure

Although it is generally accepted that a decrease in plasma oncotic pressure may result in the formation of peripheral edema, the effect of a hypo-oncotic state on brain water content is less well known. Therefore, utilizing the technique of hollow-fiber plasma-pheresis to manipulate plasma composition, the authors examined the effects of acute changes in either plasma osmolality or colloid oncotic pressure on the EEG, regional cerebral blood flow, intracranial pressure, and brain tissue specific gravity (as a measure of cerebral water content) in anesthetized, neurologically normal New Zealand white rabbits. Animals in which either osmolality or oncotic pressure was decreased by plasma replacement with an appropriate solution were compared with a group of control animals in which both of these variables were maintained constant. Animals in which plasma osmolality was decreased by 13 ± 6 mOsm/kg (from a baseline value of 295 ± 5 mOsm/kg) showed evidence of a significant increase in cortical water content (≈0.5%), whereas a 65% reduction in oncotic pressure (from 20 ± 2 mmHg to 7 ± 1 mmHg) failed to produce any change. There were no significant differences in mean arterial pressure, central venous pressure, regional cerebral blood flow, or the EEG between any of the groups. Although intracranial pressure increased in all groups, the largest increase (8.1 ± 4.4 mmHg) occurred in those animals whose osmolality was reduced. The increase in intracranial pressure in animals rendered hypo-oncotic was no different front the “control‘’ group (2.4 ± 0.9 mmHg vs. 3.0 ± 1.5 mmHg). This study suggests that an acute fall in oncotic pressure does not promote an increase in cerebral water content in the non-injured brain. Unlike peripheral tissues, the presence of the blood-brain barrier with its small pore size and limited permeability may serve to enhance the importance of osmolality and minimize the role of oncotic pressure in determining water movement between the vasculature and brain tissue.

Acute Cerebral Effects of Isotonic Crystalloid and Colloid Solutions Following Cryogenic Brain Injury in the Rabbit

Despite the numerous studies examining the relative merits of crystalloids versus colloids for expansion of intravascular volume, little attention has been directed to the cerebral effects of these solutions. In particular, the effect of changes in plasma oncotic pressure on brain water content are poorly understood. The authors recently examined the acute effects of changes in plasma osmolality and colloid oncotic pressure in normal animals, and found that a 65% reduction in oncotic pressure had no detectable effect on brain water content or intracranial pressure. In an effort to extend these studies to a more clinically relevant situation, the authors have now compared the acute effects of 0.9% saline, 6% hetastarch, and 5% albumin on regional cerebral water content and intracranial pressure in an animal model of brain injury produced by focal cortical freezing. Under general anesthesia and following the production of the cryogenic brain lesion, rabbits underwent a 45-min period of isovolemic hemodilution to a hematocrit of 20–25% with one of the three selected fluids. The saline group required approximately twice as much fluid (207 ± 17 ml) to maintain a stable mean arterial pressure and central venous pressure as did the hetastarch (105 ± 14 ml) or albumin (103 ± 29 ml) groups. As intended, the oncotic pressure decreased by a mean of 9.6 ± 2.4 mmHg in the saline group, while remaining stable in the hetastarch and albumin groups. There were no significant changes in osmolality in any group during the hemodilution period. Intracranial pressure increased in all groups following production of the cerebral lesion, but there were no differences between the various experimental groups upon conclusion of the hemodilution. Brain water content was significantly increased in the vicinity of the cryogenic lesion, but there were no differences between the various hemodilution groups. This experimental suggests that a decrease in plasma oncotic pressure due to the administration of an isotonic crystalloid solution does not acutely exacerbate the cerebral edema that is produced by this model of brain injury.

The Response of the Feline Cerebral Circulation to PaCO2 during Anesthesia with Isoflurane and Halothane and during Sedation with Nitrous Oxide

The reduction in cerebral blood flow (CBF) caused by hypocapnia is an important element of neuroanesthesic techniques. While it has been demonstrated previously that the CO2 response of the cerebral circulation (CO2 · R) is enhanced (i.e., greater ΔCBF/ΔPaCO2) during halothane administration, the effect of isoflurane on CO2 · R has not been evaluted completely. Accordingly, the authors examined CO2 · R in cats during anesthesia with 1.0 MAC isoflurane (with 75% N2O) and compared it with CO2 · R during anesthesia with 1.0 MAC halothane (with 75% N2O) and with CO2 · R during the administration of 75% N2O alone.CO2 · R during anesthesia with isoflurane–N2O was enhanced relative to that observed during administration of both halothane–N2O (P < 0.025) and N2O alone (P < .001). CO2 · R during anesthesia with halothane–N2O was, in turn, greater than that observed during the administration of N2O alone (P < 0.025). Furthermore, at similar levels of hypocapnia (PaCO2 18–20 mmHg), CBF was significantly lower (P < 0.01) during administration of isoflurane–N2O (29.0 · 4.5 ml · 100 g−1 · min−1) than during administration of either N2O (40.6 · 5.5 ml · 100 g−1 · min−1) or halothane–N2O (39.6 · 7.8 ml · 100 g−1 · min−1). CBF values during administration of the N2O alone and halothane–N2O were not different during hypocapnia.The results of this study indicate that CO2 · R in cats not only is preserved during administration of 1.0 MAC isoflurane (with 75% N2O) but is enhanced relative to that observed during anesthesia with 1.0 MAC halothane (with 75% N2O) and during sedation with N2O alone. In addition, the induction hypocapnia (PaCO2 18–20 mmHg) resulted in a reduction of CBF to lower levels during the administration of isoflurane–N2O than during administration of halothane–N2O or N2O alone. If the cerebral circulation of anesthetized humans responds similarly to that of the cat, these results suggest that the induction of hypocapnia during the administration of isoflurane (with N2O) may facilitate a greater reduction in CBF, and therefore perhaps ICP, than will occur at a comparable PaCO2 during anesthesia with halothane (with N2O) or during the administration of N2O alone.

Brain surface protrusion during enflurane, halothane, and isoflurane anesthesia in cats.

Using a noncontact displacement transducer, the authors measured protrusion of the feline cortical surface through a standardized craniotomy during acute equi-MAC exposures to enflurane, halothane, and isoflurane. Each agent was studied at 0.5, 1.0, and 1.5 MAC concentrations (plus 75% N2O) without support of blood pressure. A repeat 1.0 MAC exposure was made, during which angiotensin was infused to maintain mean arterial pressure (BP) at approximately 145 mmHg. Normocapnia was maintained during all studies. In the absence of BP support, halothane produced significantly greater protrusion of the brain surface than did equi-MAC concentrations of isoflurane at all levels and greater protrusion than enflurane at 1.0 and 1.5 MAC. Halothane-induced protrusion exceeded that seen during isoflurane administration by a factor of 2.5 at 0.5 MAC (P The results indicate that enflurane (1.0 and 1.5 MAC) and isoflurane (all levels) cause markedly less protrusion of the brain into a craniotomy than does halothane. The findings roughly parallel the known effects of these agents on cerebral blood flow and probably reflect differences in anesthetic-induced changes in cerebral blood volume. If applicable to human anesthesia, they suggest that in situations during intracranial surgery where administration of a volatile anesthetic is deemed preferable to the use of an additional fixed agent, that isoflurane may be the volatile agent of choice.

The Intracranial Pressure Effects of Isoflurane and Halo thane Administered Following Cryogenic Brain Injury in Rabbits

The intracranial pressure (ICP) responses to administration of either halothane or isoflurane were compared in New Zealand white rabbits following a standardized cryogenic brain injury. Animals were (radically intubated and paralyzed, and background anesthesia was maintained with morphine sulfate and nitrous oxide. Following injury and attainment of an elevated and stable ICP, animals were divided into four groups. Animals in groups I and III were maintained normocapnic throughout the experiment and administered 1 MAC halothane or isoflurane, respectively. Group II and IV animals were made hypocapnic (Paco2 = 20 mmHg) prior to the administration of either 1 MAC halothane or isoflurane, respectively. Monitored variables were mean arterial blood pressure, ICP (ventriculostomy), end-tidal (ET) CO2, ET volatile anesthetic, the electroencephalogram, temperature, and arterial blood gases. Prior to producing the lesion, ICP was approximately 5 mmHg in all animals with no differences among groups. Sixty to ninety minutes after injury, ICP increased significantly to approximately 20 mmHg in all animals. Introduction of either halothane or isoflurane was associated with significant increases in ICP in all groups to approximately 30 mm Hg. These data suggest that further significant increases in ICP may occur following introduction of either halothane or isoflurane in the presence of acute brain injury and elevated ICP. Furthermore, these ICP increases may not be altered by the prior establishment of hypocapnia.

Multimodality treatment of deep periventricular cerebral arteriovenous malformations

The surgical treatment of arteriovenous malformations (AVMs) located in deep periventricular regions such as the basal ganglia is associated with marked morbidity and mortality. Approaches through critical brain regions afford limited exposure of the lesions, while surgical dissection is sometimes complicated by acute severe brain swelling and/or hemorrhage in the surrounding tissues. In our approach to deep AVMs, our regimen has evolved from direct staged microsurgical excision under routine fentanyl-N2O-relaxant anesthesia (first four patients) to the use of elective high-dose barbiturate anesthesia (subsequent 12 patients). In the first group of four patients, 11 operations were performed. Two patients improved, one of whom returned to normal neurologically. There were three episodes of acute brain swelling and/or hemorrhage. One patient died as a result, and another deteriorated. In the second group of 12 patients, all but two lesions were completely excised. Among the 10 patients in whom the AVM was completely excised, seven improved, six of whom achieved a good to excellent outcome, with two regaining full neurologic function. Three patients worsened (one as the result of acute brain swelling and/or hemorrhage). There was no death in this group. Only one incidence of acute brain swelling and/or hemorrhage occurred in 26 operations. Even though the number of patients is too small in the first group for meaningful statistical comparison, our intraoperative observations and postoperative results suggest that our evolved multimodality regimen, such as staged excision and the use of elective high-dose barbiturates, was likely to have contributed to the improved treatment results of these formidable lesions.

Cerebrovascular effects of prolonged hypocarbia and hypercarbia after experimental global ischemia in cats.

Hyperventilation therapy is often recommended after an episode of global cerebral ischemia (cardiac arrest), even though several workers have shown that under such circumstances the cerebral vasculature is unresponsive to changing Paco2. However, no study has examined the effects of prolonged Paco2 changes. We therefore studied the cerebrovascular effects of a 3-h period of continuous hypercarbia (40 to 45 torr) or hypocarbia (15 to 20 torr) in cats resuscitated from 12 min of electrically induced ventricular fibrillation. There were no differences in postresuscitation cerebral blood flow (CBF) or EEG, but intracranial pressure was lower in the hypocapnic animals. Furthermore, hypocapnic cats retained some CBF responsiveness to varying Paco2 levels, while no such response was noted in previously hypercapnic animals. These findings suggest that some measurable changes in postarrest cerebrovascular behavior can result from prolonged hypocapnia (possibly related to tissue pH alterations). Whether such changes will have clinical utility is unclear.