Rene Tempelhoff

Pro- and Anticonvulsant Effects of Anesthetics (Part I)

Many inhaled anesthetics and intravenous analgesics have been alleged to produce both proconvulsant and anticonvulsant activity in humans. The reasons for these contrasting actions on the CNS are poorly understood at the present time. However, biologic variability plays an important role in determining individual patients responses to anesthetic and analgesic drugs. In addition, variations in the responsiveness of inhibitory and excitatory neurons to the central depressant effects of these drugs could also explain these apparently conflicting data. Depending on the brain concentration, centrally active drugs may produce differing effects on the CNS inhibitory and excitatory neurotransmitter systems. The availability of increasingly powerful magnetic resonance imaging techniques to provide noninvasive information about tissue chemistry (e.g., neurotransmitters and citric acid cycle metabolites) and positron emission tomography to noninvasively evaluate CNS drug-receptor interactions should lead to a more in-depth understanding of the in vivo effects of anesthetics and analgesics on the CNS. In the second part of this review article, we discuss the pro- and anticonvulsant effects of the sedative-hypnotics, local anesthetics, and other anesthetic adjuvant drugs.

Postoperative ischemic optic neuropathy

A lthough uncommon, alteration in vision or blindness after anesthesia, particularly after open heart surgery, is well documented in the nonanesthesiology literature (l-17) (Table 1). In some series, the incidence of postoperative visual loss varies between 0.1% and 1% (1,10,14). Recent retrospective reviews demonstrate one case in 56,000 surgical procedures at one university hospital (18) and six cases over a lo-yr period at another (3). The recent rate of reporting may be low due to anesthesiologists’ concerns regarding litigation, and ophthalmologists’ opinion that the occurrence of visual defect after general anesthesia is well established and unremarkable. Anesthesia texts limit their discussion of postoperative visual loss to pressure-related eye injuries associated with positioning (19,20). However, in recent years, the most commonly reported cause of postoperative visual loss is, in fact, ischemic optic neuropathy. Apart from two case reports (3,17), this devastating complication has not been addressed in the anesthesiology literature. Since the anesthesiologist must maintain the patients’ safety during surgery, a better understanding of ischemic optic neuropathy is warranted. This paper focuses on the neurovascular-ophthalmologic mechanisms responsible for postoperative loss of vision. We will review neurovascular-ophthalmic anatomy and the etiology of postoperative ischemic optic neuropathy. Although the visual prognosis of ischemic optic neuropathy is usually grim, we will discuss possible treatment modalities and preventative measures, which in some cases are straightforward, such as ensuring physical protection of the orbit. Others involve more controversial issues, specifically the safe level of hematocrit and arterial blood pressure for the maintenance of perfusion to the visual apparatus (3).

The Effect of Prone Positioning on Intraocular Pressure in Anesthetized Patients

Background Ocular perfusion pressure is commonly defined as mean arterial pressure minus intraocular pressure (IOP). Changes in mean arterial pressure or IOP can affect ocular perfusion pressure. IOP has not been studied in this context in the prone anesthetized patient. Methods After institutional human studies committee approval and informed consent, 20 patients (American Society of Anesthesiologists physical status I–III) without eye disease who were scheduled for spine surgery in the prone position were enrolled. IOP was measured with a Tono-pen® XL handheld tonometer at five time points: awake supine (baseline), anesthetized (supine 1), anesthetized prone (prone 1), anesthetized prone at conclusion of case (prone 2), and anesthetized supine before wake-up (supine 2). Anesthetic protocol was standardized. The head was positioned with a pinned head-holder. Data were analyzed with repeated-measures analysis of variance and paired t test. Results Supine 1 IOP (13 ± 1 mmHg) decreased from baseline (19 ± 1 mmHg) (P < 0.05). Prone 1 IOP (27 ± 2 mmHg) increased in comparison with baseline (P < 0.05) and supine 1 (P < 0.05). Prone 2 IOP (40 ± 2 mmHg) was measured after 320 ± 107 min in the prone position and was significantly increased in comparison with all previous measurements (P < 0.05). Supine 2 IOP (31 ± 2 mmHg) decreased in comparison with prone 2 IOP (P < 0.05) but was relatively elevated in comparison with supine 1 and baseline (P < 0.05). Hemodynamic and ventilatory parameters remained unchanged during the prone period. Conclusions Prone positioning increases IOP during anesthesia. Ocular perfusion pressure could therefore decrease, despite maintenance of normotension.

Intracranial pressure during induction of anaesthesia and tracheal intubation with etomidate-induced EEG burst suppression.

This study was designed to determine if induction of anaesthesia with etomidate titrated to an early EEG burst suppression pattern would produce minimal changes in cerebral perfusion pressure, and prevent increases in intracranial pressure (ICP) associated with tracheal intubation. Eight patients, 18–71 yr, with intracranial space-occupying lesions, were studied. In each patient ICP was monitored via a lateral ventriculostomy catheter placed preoperatively. In the operating room, an ECG, a radial arterial line, and a two-channel computerized EEG were placed. Control (awake) measurements of MAP (mmHg), ICP (mmHg), CPP(mmHg), heart rate (HR-bpm), EEG power(picowatts-pW), and spectral edge frequency (SEF, Hz) were obtained. Anaesthesia was induced with etomidate, 0.2 mg · kg−1 iv, followed immediately by an etomidate infusion, 20 mg · min−1, iv, and vecuronium 0.2 mg · kg−1 iv. When early burst suppression was achieved, the etomidate infusion was stopped and tracheal intubation performed. The etomidate dose (bolus plus infusion) required to reach burst suppression was 1.28 ± 0.11 mg · kg−1. Compared with awake control values (mean ± SE), the period from induction to burst suppression was associated with a 50% decrease in ICP (22 ± 1 vs 11 ± 1 mmHg, P < 0.01), but there were no changes in MAP, CPP, or HR. The decrease in ICP was maintained during the first 30 sec and the following 60 sec after intubation as MAP and HR remained unchanged. Our results suggest that when etomidate was administered to early burst suppression pattern on EEG, minimal changes in CPP occurred during induction of anaesthesia and a marked reduction in ICP was maintained following tracheal intubation.AbstractCette étude a été entreprise afin de déterminer si l’induction de l’anesthésie avec l’étomidate, dosé pour provoquer un début de suppression des ondes à l’EEG, produirait des changements minimes de la pression de la perfusion cérébrale, et préviendrait les augmentations de tension intrâcrdnienne (ICP) associées à l’intubation endotrachéale. Huit patients agés de 18 à 71 ans et avec une lésion intracrânienne expansive, ont été étudiés. Dans chaque cas, la tension intracrânienne, était surveillée à l’aide d’un cathéter inséré avant la chirugie à l’aide d’une ventriculostomie latérale. Après l’installation en salle d’opération d’un ECG, d’une ligne artérielle radiale et d’un EEG informatisé à deux canaux, des mesures de contrôle (à l’état d’éveil) de la tension artérielle moyenne (MAP) (mmHg), de la pression de la perfusion cérébrale (CPP) (mmHg), de la fréquence cardiaque (HR — bpm), de la puissance de l’EEG (picowatts-p W) et de la fréquence de l’extrémité du spectre («spectral edge») (SEF, Hz) était obtenues. L’anesthésie était induite avec l’étomidate à raison de 0,2 mg · kg−1 iv, suivie d’une perfusion d’étomidate à 20 mg · kg−1 iv.et de vécuronium à 0,2 mg · kg−1 iv. Lorsque la suppression des ondes de l’EEG était obtenue, la perfusion d’étomidate était cessée et on procédait à l’intubation endotrachéale. La dose d’étomidate (bolus et perfusion) requise pour supprimer les ondes à l’EEG était de 1,28 ± 0,11 mg · kg−1. Comparativement aux valeurs de contrôle à l’état d’éveil (moyenne ± SE), la période entre l’induction et la suppression des ondes de l’EEG était associée à une diminution de 50% de l’ICP (22 ± 1 vs 11 ± 1 mmHg, P < 0,01), mais il n’y avait aucun changement de MAP, CPP, ou HR. La diminution de l’ICP était maintenue pendant les 30 premières secondes, et une minute après l’intubation, alors que la MAP et le HR demeuraient inchangés. Nos résultats suggèrent que lorsque l’étomidate est administré et dosé jusqu’ à la suppression des ondes à l’EEG, des changements minimes dans la CPP apparaissent avec l’induction de l’anesthésie et une réduction marquée de l’ICP est maintenue suite à l’intubation trachéale.

Stable and dynamic cortical electrophysiology of induction and emergence with propofol anesthesia

The mechanism(s) by which anesthetics reversibly suppress consciousness are incompletely understood. Previous functional imaging studies demonstrated dynamic changes in thalamic and cortical metabolic activity, as well as the maintained presence of metabolically defined functional networks despite the loss of consciousness. However, the invasive electrophysiology associated with these observations has yet to be studied. By recording electrical activity directly from the cortical surface, electrocorticography (ECoG) provides a powerful method to integrate spatial, temporal, and spectral features of cortical electrophysiology not possible with noninvasive approaches. In this study, we report a unique comprehensive recording of invasive human cortical physiology during both induction and emergence from propofol anesthesia. Propofol-induced transitions in and out of consciousness (defined here as responsiveness) were characterized by maintained large-scale functional networks defined by correlated fluctuations of the slow cortical potential (<0.5 Hz) over the somatomotor cortex, present even in the deeply anesthetized state of burst suppression. Similarly, phase-power coupling between θ- and γ-range frequencies persisted throughout the induction and emergence from anesthesia. Superimposed on this preserved functional architecture were alterations in frequency band power, variance, covariance, and phase–power interactions that were distinct to different frequency ranges and occurred in separable phases. These data support that dynamic alterations in cortical and thalamocortical circuit activity occur in the context of a larger stable architecture that is maintained despite anesthetic-induced alterations in consciousness.

Visual Loss after Spine Surgery: A Survey

OBJECTIVE To survey a large number of neurosurgical spine surgeons for data regarding the presence of risk factors in patients experiencing visual loss after spine surgery. METHODS A survey was sent to current members (as of 1997) of the American Association of Neurological Surgeons/Congress of Neurological Surgeons, Section on Disorders of the Spine and Peripheral Nerves, with questions focusing on intraoperative factors that may predispose patients to perioperative visual loss. RESULTS Two hundred ninety surveys were returned, and 24 patients with visual loss after spine surgery were reported by 22 surgeons. Although many of these patients had probable causative factors for visual loss after surgery (e.g., hypotension, low hematocrit level, coexisting disease), some did not (n = 8). CONCLUSION These results suggest the necessity of a high index of suspicion for evolving perioperative visual loss even in the absence of risk factors.

Anticonvulsant therapy increases fentanyl requirements during anaesthesia for craniotomy

This study was designed to determine whether patients receiving chronic anticonvulsant therapy demonstrate an altered requirement for fentanyl during anaesthesia. Sixty-one patients undergoing craniotomy were studied; 20 controls (MED = 0) who had never received anticonvulsants and 41 epileptics in whom therapeutic plasma concentrations of either one (MED = 1), two (MED = 2), or three (MED = 3) different anticonvulsants were documented. During anaesthesia with 60–70 per cent N2O in O2 and 0.2 per cent isoflurane, a maintenance dose (MD) of fentanyl was administered using a continuous variable-rate IV fentanyl infusion, supplemented by intermittent 50 μg IV boluses. In order to define the minimal dosage of fentanyl required, the MD was titrated according to increases or decreases in the heart rate and/or mean arterial pressure exceeding 15 per cent of baseline ward values. A progressively higher fentanyl MD was required in the epileptic patients (MED = 1 − 4.3 ± 0.5 μg · kg− 1 · hr− 1;MED = 2 − 5.4 ± 0.6; MED = 3 − 7.6 ± 0.6) compared with the control MD (MED = 0 − 2.6 ± 0.5) (P < 0.001). These findings indicate that there appears to be a dose- effect relationship between the number of anticonvulsants received and the maintenance dose of fentanyl required during balanced anaesthesia.RésuméLe but de cette étude est d’observer les effets du traitement anticonvulsant de longue durée sur la dose de fentanyl requise pendant l’anesthésie. Soixante et un malades pour chirurgie intracranienne ont été etudiés de façon prospective: 20 patients controle (MED = 0) qui n’ont jamais recus d’anticonvulsant et 41 épileptiques avec des niveaux plasmatiques thérapeutiques pour un (MED = 1), deux (MED = 2) ou trois (MED = 3) anticonvulsants. La maintenance de l’anesthésie était assurée avec 70 pour cent N2O- O2, 0,2 pour cent isoflurane et une perfusion intraveineuse à niveau variable de fentanyl supplementée par des bolus intermittents de 50 μg. De manière a définir le dosage minimum de fentanyl requis (sans tenir compte du traitement anticonvulsant), la dose de maintenance de fentanyl (MD = perfusion + bolus) était augmentée ou diminuée selon les variations du rythme cardiaque et ou de la pression artérielle moyenne, pour les maintenir dans des limites n’éxcèdant pas ± 15 pour cent de leurs valeurs preop obtenues dans le service. Une augmentation progressive de la MD de fentanyl a été requise chez les patients épileptiques des differents groupes (MED = 1 − 4,3 ± 0,5 μg · kg− 1 · hr− 1; MED = 2 − 5,4 ± 0,6; MED = 3 − 7,6 ± 0,6) quand comparé au groupe contrôle (MED = 0− 2,6 ± 0,5) (P < 0.001). Aucune différence significative entre le groupe contrôle et les patients épileptiques, ne fut notée concernant les differents critères d’émergence de l’anesthésie. Ces resultats semble indiquer qu’il existe une relation dose- effet entre le nombre d’anticonvulsants recus par les malades et la dose de maintenance de fentanyl requise pendant l’anesthésie générate « balancée ».

INTRAVENOUS AGENTS AND INTRAOPERATIVE NEUROPROTECTION: Beyond Barbiturates

The authors discuss the role of intravenous anesthetic agents in brain protection. The newer intravenous anesthetics, etomidate and propofol, have been proposed as neuroprotective agents. Thiopental remains the drug of choice, however, for use prior to intraoperative ischemic events. The anesthetic ketamine presents surprising similarities to other N-methyl-D-aspartate receptor inhibitors, but remains controversial in its use in neurologically compromised patients.

Propofol vs. thiopental-isoflurane for neurosurgical anesthesia: comparison of hemodynamics, CSF pressure, and recovery.

Sixty otherwise healthy patients with no clinical signs of intracranial hypertension who were undergoing elective intracranial surgery were randomly assigned to receive anesthesia with either thiopental, 3-6 mg/kg i.v., and isoflurane, 0.5-1.5% (group 1, N = 30) or propofol, 1-2.5 mg/kg i.v., and propofol infusion, 40-200 microg/kg/h (group 2, N = 30). Both groups received 50% nitrous oxide in O2 subsequent to dural opening. During induction, the changes in heart rate (HR), mean arterial pressure (MAP), cerebrospinal fluid pressure (CSFP), and cerebral perfusion pressure (CPP) were similar between the groups, except at 3 min when the findings (mean +/- SEM) for CPP (81 +/- 3.3 vs. 70.3 +/- 2.8 mm Hg, p <0.05) were significantly lower in group 2. At intubation, the highest level of MAP (103.1 +/- 3.3 vs. 88.9 +/- 2.7 mm Hg, p <0.05) was significantly greater in group 1. At pinhead-holder application, the highest values of HR (81.8 +/- 3 vs. 73.9 +/- 2.1 beats/min, p <0.05), MAP (112.2 +/- 3.6 vs. 98.3 +/- 3 mm Hg, p <0.05), CSFP (15.2 +/- 1.3 vs. 11.6 +/- 1.1 mm Hg, p <0.05), and CPP (97.0 +/- 3.9 vs. 86.7 +/- 3.3 mm Hg, p <0.05) were significantly greater in group 1. During early (20-30 min) recovery, group 2 had higher Glasgow Coma Scale scores and a greater percentage of patients in whom eye opening, response to commands, extubation, speech, and time/space orientation were present. In conclusion, when compared to thiopentalisoflurane for intracranial surgery, propofol produces similar HR, MAP, CSFP, and CPP responses during induction, adequate control of these responses during nociceptive stimulation, and faster recovery for cerebral function postoperatively.

Anesthesia for carotid endarterectomy: a survey.

Summary Indications for carotid endarterectomy (CEA) have been expanded recently, and a consensus statement has been made regarding these changes. However, the debate regarding the “ideal” anesthetic for CEA remains on-going. This study was designed to evaluate the actual anesthetic techniques used by anesthesiologists for CEA. A total of 426 1-page questionnaires were mailed to all current (1995) members of the Society of Neurosurgical Anesthesia and Critical Care (SNACC). Of these, 216 (50.7%) were completed and returned. The majority of these respondents (84.7%) administered general anesthesia (GA) for CEA. Regional anesthesia (RA) was the anesthetic method of choice for 16.7%, whereas 2.8% each chose either local anesthesia (LOC) or a combined regional/general (RA/GA) technique. Despite the controversial role of nitrous oxide in neuroanesthesia, 74.6% of those returning the survey use nitrous oxide during CEA. Intraoperative neuromonitoring use was reported by 90% of the respondents, with the electroencephalography (EEG) the favored modality (67.5%). Specific intraoperative neuroprotective measures were provided by only 22.2% of all respondents, with barbiturates as the favorite method (50.0%). The technique of intraoperative hypertension is practiced by a majority of those surveyed (61.1%), with the most common target blood pressures being either preoperative baseline or preoperative baseline plus 20%. Although there is some trend towards nonintensive care setting for postoperative care, the intensive care remains the location of choice for overnight care of CEA patients (71.8%). The results of this study show that despite arguments for RA over GA, the majority of anesthesiologists surveyed choose GA for CEA.