Guy Edelman

Brain tissue oxygen, carbon dioxide, and pH in neurosurgical patients at risk for ischemia.

A sensor that measures oxygen pressure (PO2), carbon dioxide pressure (PCO2), and pH was evaluated in brain tissue of patients at risk for ischemia.The sensor is 0.5 mm in diameter and was inserted into cortex tissue in 14 patients undergoing craniotomy for cerebrovascular surgery. A compromised cerebral circulation was identified in 8 of 14 patients by single photon emission computed tomography (SPECT) scan, cerebral angiography, and transient ischemic episodes before surgery. Under baseline conditions with isoflurane anesthesia and normal blood gases, tissue PO2 was lower in the eight compromised compared to six noncompromised patients (noncompromised 37 +/- 12 mm Hg, compromised 10 +/- 5 mm Hg; P < 0.05), PCO2 was increased (noncompromised 49 +/- 5 mm Hg, compromised 72 +/- 23 mm Hg; P < 0.05), and pH was decreased (noncompromised 7.16 +/- 0.08, compromised 6.82 +/- 0.21; P < 0.05). Critical tissue values for the identification of ischemia were a PO2 of 20 mm Hg, PCO2 of 60 mm Hg, and a pH of 7.0. These results suggest that brain tissue measures of PO2, PCO2, and pH provide information on the adequacy of cerebral perfusion in neurosurgical patients. (Anesth Analg 1996;82:582-6)

Bupivacaine Inhibits Acylcarnitine Exchange in Cardiac Mitochondria

Background The authors previously reported that secondary carnitine deficiency may sensitize the heart to bupivacaine-induced arrhythmias. In this study, the authors tested whether bupivacaine inhibits carnitine metabolism in cardiac mitochondria. Methods Rat cardiac interfibrillar mitochondria were prepared using a differential centrifugation technique. Rates of adenosine diphosphate–stimulated (state III) and adenosine diphosphate–limited (state IV) oxygen consumption were measured using a Clark electrode, using lipid or nonlipid substrates with varying concentrations of a local anesthetic. Results State III respiration supported by the nonlipid substrate pyruvate (plus malate) is minimally affected by bupivacaine concentrations up to 2 mM. Lower concentrations of bupivacaine inhibited respiration when the available substrates were palmitoylcarnitine or acetylcarnitine; bupivacaine concentration causing 50% reduction in respiration (IC50 ± SD) was 0.78 ± 0.17 mM and 0.37 ± 0.03 mM for palmitoylcarnitine and acetylcarnitine, respectively. Respiration was equally inhibited by bupivacaine when the substrates were palmitoylcarnitine alone, or palmitoyl–CoA plus carnitine. Bupivacaine (IC50 = 0.26 ± 0.06 mM) and etidocaine (IC50 = 0.30 ± 0.12 mM) inhibit carnitine-stimulated pyruvate oxidation similarly, whereas the lidocaine IC50 is greater by a factor of roughly 5, (IC50 = 1.4 ± 0.26 mM), and ropivacaine is intermediate, IC50 = 0.5 ± 0.28 mM. Conclusions Bupivacaine inhibits mitochondrial state III respiration when acylcarnitines are the available substrate. The substrate specificity of this effect rules out bupivacaine inhibition of carnitine palmitoyl transferases I and II, carnitine acetyl- transferase, and fatty acid &bgr;-oxidation. The authors hypothesize that differential inhibition of carnitine-stimulated pyruvate oxidation by various local anesthetics supports the clinical relevance of inhibition of carnitine–acylcarnitine translocase by local anesthetics with a cardiotoxic profile.

Epinephrine impairs lipid resuscitation from bupivacaine overdose: A threshold effect

Background:Lipid emulsion infusion reverses local anesthetic-induced cardiac toxicity, but the effect of adding epinephrine has not been studied. We compared escalating doses of epinephrine on recovery with lipid infusion in a rat model of bupivacaine overdose. Methods:Rats anesthetized with isoflurane received an IV bolus of 20 mg/kg bupivacaine, producing asystole (zero time) in all animals. Ventilation (100% oxygen) and chest compressions were started immediately, and at 3 min the rats received one of six IV treatments (n = 5 for all groups): 5 ml/kg saline followed by infusion for 2 min at 1.0 ml · kg−1 · min−1, and a second 5 ml/kg bolus at 5 min; or the same bolus and infusion treatment using 30% lipid emulsion plus a single injection of epinephrine at one of five doses: 0 (lipid control), 1, 2.5, 10, or 25 mcg/kg. An electrocardiogram and arterial pressure were monitored continuously, and arterial blood gas was measured at 7.5 and 15 min. Results:Epinephrine improved initial return of spontaneous circulation (rate-pressure product > 30% baseline) but only 3 of 5 rats at 10 mcg/kg and 1 of 5 rats at 25 mcg/kg sustained return of spontaneous circulation by 15 min. Lipid alone resulted in slower but more sustained recovery. Epinephrine doses above a threshold near 10 mcg/kg increased lactate, worsened acidosis, and resulted in poor recovery at 15 min, as compared with lipid controls. There was tight correlation of epinephrine dose to serum lactate at 15 min. Conclusions:Epinephrine over a threshold dose near 10 mcg/kg impairs lipid resuscitation from bupivacaine overdose, possibly by inducing hyperlactatemia.

Cerebral autoregulation in awake versus isoflurane-anesthetized rats

We evaluated regional cerebral and spinal cord blood flow in rats during isoflurane anesthesia. Tissue blood flow was measured in cerebral cortex, subcortex, midbrain, and spinal cord using radioactive microspheres. Blood flow autoregulation was measured within the following arterial blood pressure ranges (mm Hg): 1 = less than 50, 2 = 50-90, 3 = 90-130, 4 = 130-170, 5 = greater than 170. Arterial blood pressure was increased using phenylephrine infusion and decreased with ganglionic blockade and hemorrhage. Three treatment groups were studied: 1 = awake control, 2 = 1.0 minimum alveolar anesthetic concentration (MAC) isoflurane, 3 = 2.0 MAC isoflurane. Autoregulation was seen in awake rats from 50 to 170 mm Hg in all tissues. The autoregulatory coefficient (change in blood flow/change in blood pressure) was increased in midbrain and spinal cord during 1.0 MAC isoflurane and in all tissues during 2.0 MAC isoflurane (P less than 0.05). Within the arterial blood pressure range of 90-130 mm Hg, isoflurane produced the following changes in tissue blood flow (percent of awake control): 1.0 MAC isoflurane: cortex = 87% +/- 8% (P greater than 0.30), subcortex = 124% +/- 11% (P greater than 0.05), midbrain = 263% +/- 20% (P less than 0.001), spinal cord = 278% +/- 19% (P less than 0.001); 2.0 MAC isoflurane: cortex = 137% +/- 13% (P less than 0.05), subcortex = 272% +/- 24% (P less than 0.001), midbrain = 510% +/- 53% (P less than 0.001), spinal cord = 535% +/- 50% (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Thiopental and Desflurane Treatment for Brain Protection

OBJECTIVE Thiopental produces cerebral metabolic depression and cerebral vasoconstriction. However, the effect of thiopental on brain tissue oxygen pressure (PO2), carbon dioxide pressure, and pH is not known. In a prospective study, we measured brain tissue gases and pH during thiopental or desflurane treatment that was administered for brain protection during brain artery occlusion. METHODS After institutional review board approval, 20 patients undergoing craniotomies for cerebrovascular surgery were tested; 10 were randomized to receive thiopental and 10 to receive desflurane. After each craniotomy, a Neurotrend probe (Diametrics Medical, Minneapolis, MN) was inserted to measure tissue PO2, carbon dioxide pressure, and pH in a tissue region at risk to develop ischemia during temporary brain artery occlusion. Thiopental or desflurane was administered to produce burst suppression of electroencephalography, and then temporary artery occlusion was performed during aneurysm or extracerebral-to-intracerebral bypass surgery. RESULTS Thiopental produced no change in tissue gases or pH, but temporary artery clipping in thiopental-treated patients decreased PO2 30% (P < 0.05). Desflurane increased PO2 70% (P < 0.05), and tissue oxygenation remained elevated during temporary artery occlusion. Tissue pH did not decrease in either group during temporary brain artery occlusion. CONCLUSION Thiopental has a metabolically neutral effect on brain tissue gases and pH, even though it is known to decrease cerebral oxygen consumption. The metabolic depressant and vasodilator effects of desflurane enhance tissue oxygenation and attenuate tissue PO2 reductions produced by artery occlusion. Both thiopental and desflurane inhibit ischemic lactic acidosis and decreases in pH.

Comparison of the effect of etomidate and desflurane on brain tissue gases and pH during prolonged middle cerebral artery occlusion

Background The authors compared the effects of etomidate and desflurane on brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2), and pH in patients who had middle cerebral artery occlusion for > 15 min. Methods After a craniotomy, a probe that measures PO2, P (CO)2, and pH was inserted into cortical tissue at risk for ischemia during middle cerebral artery occlusion. A burst suppression pattern of the electroencephalogram was induced with etomidate (n = 6) or 9% end‐tidal desflurane (n = 6) started before middle cerebral artery occlusion. Mean blood pressure was supported with phenylephrine to 90–95 mmHg. Results During baseline conditions, tissue PO2, PCO (2), and pH were similar between the two groups (PO2 = 15 mmHg, PCO2 = 60 mmHg, pH = 7.1). During administration of etomidate before middle cerebral artery occlusion, tissue PO2 decreased in five of six patients without a change in PCO2 or pH. During administration of 9% desflurane, tissue PO2 and pH increased before middle cerebral artery clipping. Middle cerebral artery occlusion for an average of 33 min with etomidate and 37 min with desflurane produced a decrease in pH with etomidate (7.09 to 6.63, P <0.05) but not with desflurane (7.12 to 7.15). Conclusion These results suggest that tissue hypoxia and acidosis are often observed during etomidate treatment and middle cerebral artery occlusion. Treatment with desflurane significantly increases tissue P (O)2 alone and attenuates acidotic changes to prolonged middle cerebral artery occlusion.

Clinical Patterns and Outcome in Epithelioid Hemangioendothelioma With or Without Pulmonary Involvement: Insights From an Internet Registry in the Study of a Rare Cancer

BACKGROUND Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm of endothelial origin with clinical behavior intermediate between hemangioma and angiosarcoma. The natural history of EHE is highly variable. This study uses an Internet registry to identify clinical patterns with prognostic significance in EHE. METHODS Cases from the International Hemangioendothioma, Epithelioid Hemangioendothelioma, and Related Vascular Disorders (HEARD) Support Group were evaluated based on demographics, organ involvement, disease progression, presence or absence of pleural effusion, and treatment. Survival among various cohorts was compared using log-rank analysis of Kaplan-Meier plots. RESULTS Two hundred sixty-four patients were identified from April 2004 to November 2009. Fifty-eight cases were excluded because of inadequate information or wrong diagnosis. EHE was more common in female patients (61%). Male gender and age ≥ 55 years were associated with decreased survival. The most commonly affected organs were liver, lung, and bone. No specific organ or combination of organ involvement differentially affected survival, and survival was no different between patients with multiple vs single organ involvement. However, pattern B, defined as lesions without distinct borders (eg, pulmonary infiltrates, pleural effusion, ascites), hemoptysis, or involvement of more than two bones adversely affected survival in all cohorts. CONCLUSION A novel staging system with prognostic value for EHE is proposed. Pleural effusion or other signs of uncontained tumor growth, hemoptysis, and osseous involvement of more than two bones implied worse survival than did localized and discrete tumors, regardless of number of organs involved. A lay registry can provide useful insights into the clinical behavior of a rare cancer.

Hypoxic Brain Tissue following Subarachnoid Hemorrhage

Background Subarachnoid hemorrhage can lead to cerebral ischemia and irreversible brain injury. The purpose of this study was to determine whether subarachnoid hemorrhage produces changes in brain tissue oxygen pressure, carbon dioxide pressure, or pH during surgery for cerebral aneurysm clipping. Methods After institutional review board approval and patient consent, 30 patients undergoing craniotomy for cerebral aneurysm clipping were studied, 15 without and 15 with subarachnoid hemorrhage. Patients with subarachnoid hemorrhage were prospectively separated into groups with modest (Fisher grade 1 or 2; n = 8) and severe bleeds (Fisher grade 3; n = 7). After a craniotomy, a probe was inserted into cortex tissue supplied by the artery associated with the aneurysm. Baseline measures were made in the presence of a 4% end-tidal desflurane level. The end-tidal desflurane level was increased to 9% before clipping of the aneurysm, and a second tissue measurement was made. Results The median time of surgery after subarachnoid hemorrhage was 2 days, ranging from 1 to 13 days. During baseline anesthesia, brain tissue oxygen pressure was 17 ± 9 mmHg (mean ± SD) in control patients, 13 ± 9 mmHg in those with Fisher grade 1 or 2 hemorrhage, and 7 ± 6 mmHg in those with Fisher grade 3 hemorrhage (P < 0.05 compared with control). Brain tissue pH was 7.10 ± 0.10 in control patients, 7.14 ± 0.13 in those with Fisher grade 1 or 2 hemorrhage, and 6.95 ± 0.18 in those with with Fisher grade 3 hemorrhage (P < 0.05). At a 9% end-tidal desflurane level, brain tissue oxygen pressure increased to 19 ± 9 mmHg and brain tissue pH increased to 7.11 ± 0.11 in patients with Fisher grade 3 hemorrhage (P < 0.05 for both increases). Conclusion These results show that subarachnoid hemorrhage can significantly decrease brain tissue oxygen pressure and pH related to the severity of the bleed. Increasing the desflurane concentration to 9% increased brain tissue oxygen pressure in all patients and brain tissue pH in patients with subarachnoid hemorrhage with baseline acidosis.

Brain tissue gases and pH during arteriovenous malformation resection.

OBJECTIVE The purpose of this study was to determine whether baseline partial pressure of oxygen (PO2), partial carbon dioxide pressure (PCO2), and pH in brain tissue adjacent to arteriovenous malformations (AVMs) are different from those in control patients. In addition, PO2, PCO2, and pH changes were measured during resection of the AVMs. METHODS Two groups were studied. Group 1 (n = 8) was composed of nonischemic patients scheduled for cerebral aneurysm clipping. Group 2 (n = 13) was composed of patients undergoing neurosurgery for resection of AVMs. After the craniotomy, the dura was retracted and a combined PO2, PCO2, and pH sensor was inserted into nonischemic brain tissue in Group 1. In Group 2, the sensor was inserted into tissue 2 to 3 cm from the margin of the AVMs, within the same arterial blood supply. After equilibration of the sensor, tissue gases and pH were measured during steady-state anesthetic conditions in Group 1 and during resection of AVMs in Group 2. RESULTS Under baseline conditions before the start of surgery, tissue PO2 was decreased in patients with AVMs compared with control patients, but PCO2 and pH were not changed. During resection of the AVMs, PO2 and pH increased and PCO2 decreased compared with baseline measurements. These parameters did not change in control patients during a similar time period. CONCLUSION The results suggest that cerebrovascular or metabolic adaptation occurs in patients with AVMs with decreased tissue perfusion pressure as an adjustment for decreased oxygen delivery. During resection of AVMs, this adaptation produces a relative hyperemic environment with tissue hyperoxia, hypocapnia, and alkalosis that is not corrected by the end of surgery.

Brain tissue oxygen pressure, carbon dioxide pressure and pH during ischemia

In this case we evaluated brain tissue pO2, pCO2 and pH during ischemia and arterial oxygen desaturation (hypoxia). In both situations brain pO2 decreased. During ischemia, tissue pCO2 increased while pH decreased; but both pCO2 and pH were stable during hypoxia. These results suggest that brain tissue pO2, pCO2 and pH measures provide information on tissue perfusion and oxygen availability during ischemia and hypoxia.