Concezione Tommasino

Local cerebral blood flow and glucose utilization during isoflurane anesthesia in the rat

Volatile anesthetic agents have profound and heterogeneous effects on global and local cerebral blood flow (I-CBF) and metabolism. The relationship between I-CBF and local cerebral glucose uptake (I-CMRg) during isoflurane anesthesia is unknown. Because these relationships might influence neuronal homeostasis during periods of cerebral ischemia of different causes, it becomes important to understand them. Accordingly, the authors evaluated the I-CBF and I-CMRg effects of isoflurane with quantitative autoradiography in normal rats. As the dose of isoflurane increased in a stepwise fashion to 0.5, 1.0 (1.38%), 1.5, and 2.0 MAC levels, the number of structures with a significant (P < 0.05) I-CBF increase or I-CMRg decrease became greater. At each respective MAC level I-CBF was increased in 0%, 11%, 34%, and 30%, while I-CMRg decreased in 11%, 70%, 74%, and 81% of the structures in which autoradiographic measurements were performed. Between 1.5 MAC and 2.0 MAC the I-CMRg decrease stabilized at about −50% to −70% of cerebral metabolic values obtained in awake control rats in association with attainment of a burst-suppression of isoelectric electroencephalogram. In contrast to these general changes, I-CMRg in two subcortical limbic system structures (dentate gyrus and interpeduncular nucleus) did not decrease, even at the highest doses of isoflurane. L-CBF was significantly (P < 0.05) increased only at the highest dose ranges (1.5–2.0 MAC) and increased from 34% to 238% in about one-third of the structures evaluated. Isoflurane anesthesia causes heterogeneous changes in I-CBF and metabolism, which are most apparent at doses at or above 1.0 MAC. Differences in I-CBF/I-CMRg ratio patterns during isoflurane anesthesia suggest, at least in part, that cerebral flow and metabolic changes may proceed through unrelated regulatory mechanisms.

Regional cerebral metabolism of glucose in comatose and vegetative state patients

Regional cerebral metabolism of glucose (rCMRglu) was evaluated in patients who were in a coma and vegetative state to determine the level of brain function during these conditions. rCMRglu was measured in 17 discrete brain regions with (/-) [18F] -fluoro-2-deoxy-D-glucose (FDG) and positrn emission tomography (PET) in 15 patients with ;brain pathology subsequent to cardiorespiratory arrest (CA), head trauma (HT), or brain ischemia (BI) resulting from cerebrovascular accident or brain surgery. Five comatose patients (Coma group, n = 5), and 10 vegetative state patients (VS, patients awake but not aware) were studied. The VA patients were subdivided, according to the length of their VS condition, into a VS group (n = 6, < 3 months if CA or BI patients, or < 12 months if HT patients) and a persistent vegetative state group (PVS, n = 4, > 3 months if CA or BI patients of > 12 months if HT patients.) Ten normal age-matched subjects served as control. Global CMRglu was 6.72 +/- 0.93 (+/-SD) mg/100 g/min in control subjects. It was significantly (p < - 0.001) reduced to 3.70 +/- 61 in coma, to 3.45 +/- in VS, and to 2.33 +/- 0.34 mg/100 g/min in PVS patients. rCMRglu was significantly reduced (p < - 01001) from control values in all the 17 structures surveyed in every patient. In the Coma and VS groups, there was an overlapping of rCMRglu in the majority of the brain structures. (ABSTRACT TRUNCATED AT 250 WORDS)

7.5% hypertonic saline versus 20% mannitol during elective neurosurgical supratentorial procedures.

This prospective randomized clinical study was designed to compare the effects of equal volumes of 7.5% hypertonic saline solution (HS) or 20% mannitol (M) on brain bulk and lumbar cerebrospinal fluid pressure (CSFP) during elective neurosurgical procedures (aneurysm, arteriovenous malformation, or tumor). After informed consent, 50 American Society of Anesthesiologists physical Status I (ASA I) patients were randomly assigned to M (n = 25) or HS (n = 25) groups. Anesthesia protocol was identical for both, and variables monitored included mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP), CSF pressure (CSFP), arterial blood gases (PaCO2 30-35 mm Hg), serum sodium, potassium, and osmolality, and diuresis. The study period started before hypertonic solution administration (T0) and ended at the opening of the dura mater or 60 min after T0. Data were assessed with repeated measures analysis of variance and Student t test with Bonferroni correction (p < or = 0.05). MAP and CVP were the same in the two groups. After treatment, osmolality increased, and the increase at T15 was higher in HS-treated patients [316.6 +/- 9.3 vs. 304.0 +/- 12.0 (SD) mOsmol/kg; p < 0.001]. Sodium decreased after M and increased after HS. During the study, brain bulk was always considered satisfactory. CSFP was not different between M and HS groups and significantly decreased overtime (p = 0.0056) with no difference between treatments. The results of the present study demonstrate that hypertonic saline is as effective as mannitol in reducing the brain bulk and the CSFP during elective neurosurgical procedures under general anesthesia.

Intracranial effects of endotracheal suctioning in the acute phase of head injury.

In patients with head injury, endotracheal suctioning (ETS) is a potentially dangerous procedure, because it can increase intracranial pressure (ICP). The purpose of this prospective nonrandomized study was to evaluate the impact of ETS on intracranial dynamics in the acute phase of head injury. Seventeen patients with severe head injury (Glasgow Coma Score ≤ 8, range 4–8), sedated and mechanically ventilated, were studied during the first week after trauma. Single-pass ETS maneuver (with a 16-French catheter, negative pressure of 100 mm Hg, and duration of less than 30 seconds) was performed 60 seconds after the FiO 2 was increased to 100%. After ETS, FiO 2 was maintained at 100% for another 30 seconds. Before and after ETS, arterial blood gases and jugular oxygen saturation (S j O 2 ), ICP, and mean arterial pressure (MAP) were measured and cerebral perfusion pressure (CPP) was calculated. A total of 131 ETS episodes, which consisted of repeated assessment of each patient, were analyzed. Six patients in 20 cases coughed and/or moved during ETS because of inadequate sedation. After ETS, ICP increased from 20 ± 12 to 22 ± 13 mm Hg in well-sedated patients and from 15 ± 9 to 28 ± 9 mm Hg in patients who coughed and/or moved (mean change, 2 ± 6 versus 13 ± 6 mm Hg, P <.0001). CPP and S j O 2 increased in well-sedated patients (from 78 ± 16 to 83 ± 19 mm Hg, and from 71 ± 10 to 73 ± 13%, respectively) and decreased in patients who reacted to ETS (from 79 ± 14 to 72 ± 14 mm Hg and from 69 ± 7 to 66 ± 9%, respectively), and the differences were significant (mean change, CPP: 5 ± 14 versus -7 ± 15 mm Hg, P =.003; (S j O 2 ) 2 ± 5 vs. −3 ± 5%, P <.0001). In well-sedated patients, endotracheal suctioning caused an increase in ICP, CPP, and S j O 2 without evidence of ischemia. In contrast, in patients who coughed or moved in response to suctioning, there was a slight and significant decrease in CPP and S j O 2 . In the case of patients with head injuries who coughed or moved during endotracheal suctioning, we strongly suggest deepening the level of sedation before completing the procedure to reduce the risk of adverse effects.

Fentanyl-induced seizures activate subcortical brain metabolism.

Neurophysiologic studies have demonstrated epileptoid activity during high-dose narcotic anesthesia. The authors utilized the 14C-2-deoxyglucose method to evaluate the local cerebral glucose metabolism (1-CMRg) during high-dose fentanyl-induced epileptoid discharges as evaluated by electroencephalography (EEG) in ventilated rats. Fentayl was administered intravenously at two dose levels (200 μg · kg-1, n = 5; and 400 μg · kg-1, n = 8). Seven unanesthetized animals served as controls. During fentanyl administration, the EEG was characterized by the appearance of isolated high voltage (>100 μV) spike and polyspike and wave complexes at a frequency of one every 1–4 s, superimposed on a baseline of reduced frequency and voltage. Isolated ictal discharges (spike or sharp waves at a frequency of 12–20/s) rarely were superimposed upon the spike and polyspike activity.As a general trend, fentanyl administration induced a significant (P <0.05) decrease of the 1-CMRg in the majority of the 37 brain structures surveyed. A clear relationship between 1-CMRg and epileptoid activity appeared when the anatomic areas were grouped into functional systems. Cerebral metabolism was globally decreased in the visual and snesorimotor systems (53–78%), in the white matter structures (76–78%), and reticular formation (59–69%) with both fentanyl treatments. The largest deviation from this trend appeared in the limbic system. Here with both treatments, the 1-CMRg in the claustrum, septal nucleus, amygdala, and ventral areas of CA1 and CA3 of the hippocampus remained at control values. At the higher fentanyl dosage, there was a more widespread depression of 1-CMRg in the rest of the brain, while in the limbic system this effect was reversed, with the 1-CMRg returning to control values in the hippocampus (CA1), dentate gyrus, and interpeduncular nucleus.The relative hypermetabolism in limbic system structures during fentanyl-induced epileptoid activity, coupled with a significant reduction of glucose utilization in the rest of the brain, suggests a role for the limbic system in the genesis of seizure activity during fentanyl administration.

Cerebral ischemia after venous air embolism in the absence of intracardiac defects.

Cerebral air embolism occurred in a patient undergoing posterior fossa surgery performed in the sitting position for acoustic neuroma removal. The patient experienced two episodes of venous air embolism, as evidenced by precordial Doppler, end-tidal carbon dioxide reduction, and oxygen desaturation. In both cases, air was aspirated from the central venous catheter; during the second episode there was arterial hypotension and electrocardiogram changes, and air bubbles were visualized in the cerebellar arteries. The patient did not regain consciousness after surgery and developed early tonic-clonic convulsions and electroencephalogram status epilepticus, which was treated with barbiturate coma. Intracardiac septal defects were not detected by transesophageal echocardiography, and computerized tomography of the brain demonstrated multifocal discrete ischemic areas in the cerebral hemispheres. The patient died 6 days after surgery without having regained consciousness. This case appears to represent the occurrence of transpulmonary passage of venous air embolism.

Emergence times are similar with sevoflurane and total intravenous anesthesia: Results of a multicenter rct of patients scheduled for elective supratentorial craniotomy

Background Nearly every anesthetic agent has been used for craniotomy, yet the choice between intravenous or volatile agents has been considered an area of significant debate in neuroanesthesia. We designed a Randomized Clinical Trial to test the hypothesis that inhalation anesthesia (sevoflurane/remifentanil-group S) reduces emergence time by 5 minutes compared with intravenous anesthesia (propofol/remifentanil-group P) in patients undergoing neurosurgery for supratentorial neoplasms. Methods Adult ASA I-III elective patients were randomly assigned to group S or P. The primary outcome was time to reach an Aldrete test score (AS) of more than equal to 9; secondary outcomes were times to eyes opening (TEO) and extubation (ET), adverse events, intraoperative hemodynamics, brain relaxation score (BRS), opioid consumption, and diuresis. Results No significant differences were found between S (n=149) and P (n=153) treatments in primary outcomes: median time to reach AS=9 was 5 minutes (25th to 75th percentile 5 to 10 minutes in both groups, P≥0.05); and 15 minutes to reach AS=10 (P group 95% CI=10.3-19.7 min; S group 95% CI=11.4-18.5 min, P≥0.05) in both groups. TEO and ET expressed as median values (95% CI) were, respectively: 8 (6.8 to 9.2) minutes in group P versus 6 (4.6 to 7.4) in group S, P<0.05; 10 (9.6 to 10.4) minutes in group P versus 8 (7 to 9) in group S, P<0.05. Shivering, postoperative nausea and vomiting, pain, and seizure during the first 3 postoperative hours were not significantly different between the 2 groups, nor was BRS. Hypotension was more frequent in group S. Intraoperative diuresis and opioid consumption were greater in group P. Conclusions Sevoflurane/remifentanil neuroanesthesia is not superior to propofol/remifentanil in time to reach an AS ≥9.

Remifentanil Provides Hemodynamic Stability and Faster Awakening Time in Transsphenoidal Surgery

In this prospective study, we evaluated the effects of remifentanil in ASA I–II patients undergoing transsphenoidal surgery. After the induction of anesthesia, patients were randomly allocated to the Isoflurane (n = 22, 60% nitrous oxide, isoflurane up to 2% end-tidal) or Remifentanil group (n = 21, 60% nitrous oxide, 0.5% end-tidal isoflurane, remifentanil up to 2 &mgr;g · kg−1 · min−1). If mean arterial pressure (MAP) increased >80 mm Hg during maximal dosage of isoflurane or remifentanil, labetalol was administered. At the end of anesthesia, extubation and awakening times, respiratory rate, Spo2, MAP, heart rate, and adverse effects were recorded. Hemodynamics and bleeding (minimal, mild, moderate, severe) were not different between groups. Bleeding grade increased with MAP >80 mm Hg (P < 0.001). Labetalol was administered to 20 patients in the Isoflurane group, and 10 patients in the Remifentanil group (P < 0.01). The dose of labetalol was larger in the Isoflurane group (1.0 ± 0.6 versus 0.5 ± 0.7 mg/kg, P < 0.05). Time to extubation did not differ, whereas time to follow commands was shorter in Remifentanil patients (16 ± 8 versus 10 ± 2 min, P < 0.01). No adverse effects occurred in the early postoperative period.

Conscious sedation in the critically ill ventilated patient

PURPOSE The aim of sedation is to provide comfort and minimize anxiety. However, adverse effects are noteworthy, and the optimal end point of sedation in intensive care unit patients is still debated. We analyzed if a level 2 on the Ramsay Scale (ie, awake, cooperative, oriented, tranquil patient) is suitable for an invasive therapeutic approach. MATERIALS AND METHODS Forty-two patients requiring respiratory support and sedation for at least 4 days were enrolled in a prospective interventional cohort study aiming at maintaining patients awake and collaborative. The Ramsay score was recorded 3 times a day. Once a day, the nurse in charge evaluated adequacy of sedation according to the compliance with nursing care and therapeutic maneuvers in the previous 24 hours. Data were collected until patients were ventilated. RESULTS Overall, 264 of 582 days were classified as conscious. Sedation was adequate in 93.9% of them. In conscious days, a higher Simplified Acute Physiology Score II score and male sex significantly correlated with inadequate sedation. CONCLUSIONS In a population of severe intensive care unit patients, conscious sedation was achieved in almost half of the days spent on ventilation. The positive implications (eg, on length of weaning and cost of sedation) of a conservative sedation strategy may be highly relevant.

Local cerebral blood flow during lidocaine-induced seizures in rats.

Neurophysiologic and local cerebral metabolic mapping techniques indicate that seizures associated with lidocaine toxicity originate in subcortical brain structures. Normally local cerebral blood flow (1-CBF) is quantitatively coupled to local cerebral metabolic rate for glucose (1-CMRg). In the present study the response of 1- CBF to a lidocaine-induced preconvulsive state (localized seizure activity in the absence of a grand mal seizure) was evaluated in rats anesthetized with 60% nitrous oxide. Lidocaine administered as a bolus (20 mg/kg) followed by an infusion (4 mg/kg) over 5.5 min resulted in progressive alteration in the electroencephalogram (EEG). L-CBF was studied with the 14C-iodoantypyrine autographic method when the preconvulsive EEG pattern consisted of a repetitive spike and wave complex at a frequency of 14 ± 1 · min−1 complexes, superimposed on practically isoelectric background activity. Under these conditions high doses of lidocaine significantly (P < 0.05) decreased (range –30% to –68%) 1-CBF in 71% of the 34 brain regions studied. The greatest exception to this trend for 1-CBF to decrease was observed in the limbic system wherein 1-CBF remained within control ranges in eight of the 11 structures evaluated. Qualitative comparison of lidocaine 1-CBF changes with 1-CMRg changes obtained under similar conditions indicated a general trend for local flow and metabolism to decrease in parallel. Exceptions to this were confined to certain limbic areas (amygdala and hippocampus) in which increases in l-CMRg were more than 100% greater than slight (P > 0.05) increases in 1-CBF. This comparison demonstrates uncoupling of local brain metabolism from blood flow during lidocaineinduced subcortical epileptoid discharges (preconvulsive state) in areas recognized to be prone to irreversible damage when seizure activity is much prolonged beyond the duration of this study.