Laurel E. Moore

Venous air embolism: a review.

Abstract Venous air embolism (VAE) can be a lethal complication of surgical procedures, during which (1) venous pressure at the site of surgery is subatmospheric or (2) gas is forced under-pressure into a body cavity. Though classically associated with neurosurgery, VAE is also a potential complication of laparoscopic, pelvic, and orthopedic procedures. It is, therefore, essential for the practicing anesthesiologist to recognize and treat venous air entrainment. An in-depth review of the pathophysiology, clinical presentation, detection, prevention, and treatment of VAE is presented.

Nitro-l-Arginine Analogues Dose- and Time-Related Nitric Oxide Synthase Inhibition in Brain

BACKGROUND AND PURPOSE The purpose of the present study was to measure cortical nitric oxide synthase (NOS) activity and determine the appropriate doses of N omega-nitro-L-arginine methyl ester (L-NAME) or N omega-nitro-L-arginine (L-NNA) for near-complete enzyme inhibition in dogs, cats, and pigs. We anticipated that NOS inhibition was dose- and time-dependent and questioned if the dose-response relationship was related to the specific drug or animal species. METHODS Saline or L-NAME or L-NNA in escalating doses was administered to pentobarbital-anesthetized pigs, dogs, and cats. Brain temperature and arterial blood gas, hemoglobin, and blood pressure levels were maintained within the physiological range. Cortical tissue was biopsied at baseline and 30, 120, and 360 minutes after agent administration for measurement of NOS activity by isotopic assay of the conversion of [14C]arginine to [14C]citrulline. RESULTS L-NAME produced > 70% enzyme inhibition at a dose of 20 mg/kg across the species tested. Arterial blood pressure was elevated at 30 minutes after L-NAME treatment. However, consistent decreases in brain NOS activity required a longer period of time. Near-complete inhibition was apparent in most animals by 120 minutes and persisted for 6 hours after administration. A smaller dose of L-NNA was required for > 70% enzyme inhibition in the cats and dogs (10 mg/kg). Near-complete NOS inhibition was evident in most animals at 30 minutes after L-NNA administration, which also persisted for 6 hours. In pigs, this same level of inhibition required 20 mg/kg. CONCLUSIONS These results suggest that administration of L-NAME and L-NNA diminishes brain NOS activity in a dose- and time-dependent manner and that the duration of effect is at least 6 hours.

N omega-nitro-L-arginine methyl ester prevents cerebral hyperemia by inhaled anesthetics in dogs.

The mechanism by which halothane, isoflurane, and nitrous oxide increase cerebral blood flow (CBF) is unknown. We assessed the cerebrovascular effects of nitrous oxide (70%; n = 6), isoflurane (1 minimum alveolar anesthetic concentration: 1.4%; n = 6) or halothane (1 minimum alveolar anesthetic concentration: 0.8%; n = 6) before and after blockade of nitric oxide (NO) synthase with 40 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) intravenously in dogs with baseline pentobarbital anesthesia. Baseline CBF (microspheres) was determined after 1 h of pentobarbital anesthesia. Cerebral perfusion pressure (CPP) was maintained during inhaled anesthetic or L-NAME by either hemorrhage or inflation of an intra-aortic balloon. Before L-NAME, halothane and isoflurane increased CBF (40 +/- 4 to 56 +/- 6 mL.min-1 x 100 g-1 and 43 +/- 6 to 78 +/- 12 mL.min-1 x 100 g-1, respectively) with no change in cerebral oxygen consumption (baseline: halothane, 2.6 +/- 0.2; isoflurane, 2.0 +/- 0.2 mL.min-1 x 100 g-1). On the contrary, nitrous oxide increased CBF similarly (40 +/- 6 to 57 +/- 8 mL.min-1 x 100 g-1), but increased cerebral oxygen consumption (2.2 +/- 0.3 to 3.0 +/- 0.3 mL.min-1 x 100 g-1). L-NAME decreased blood flow in the neurohypophysis by 80% with no change in blood flow in other brain regions. After L-NAME, reexposure to nitrous oxide, halothane, or isoflurane resulted in no change in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence, predictors, and outcomes of perioperative stroke in noncarotid major vascular surgery.

BACKGROUND:Perioperative stroke is a potentially catastrophic complication of surgery. Patients undergoing vascular surgery suffer from systemic atherosclerosis and are expected to be at increased risk for this complication. We studied the incidence, predictors, and outcomes of perioperative stroke after noncarotid major vascular surgery using the American College of Surgeons National Quality Improvement Program database. METHODS:Forty-seven thousand seven hundred fifty patients undergoing noncarotid vascular surgery from 2005 to 2009 at nonVeterans Administration hospitals were identified from the American College of Surgeons National Quality Improvement Program database. An analysis of patients undergoing elective lower extremity amputation, lower extremity revascularization, or open aortic procedures was performed to determine the incidence, independent predictors, and 30-day mortality of perioperative stroke. RESULTS:The overall incidence of perioperative stroke within 30 days of surgery (n = 37,927) was 0.6%. Multivariate analysis revealed that each 1-year increase in age [odds ratio 1.02, 95% confidence interval (CI) (1.01 to 1.04)], cardiac history [1.42, (1.07 to 1.87)], female sex [1.47, (1.12 to 1.93)], history of cerebrovascular disease [1.72, (1.29 to 2.29)], and acute renal failure or dialysis dependence [2.03, (1.39 to 2.97)] were independent predictors of stroke. Only 15% (95% CI, 11%–20%) of strokes occurred on postoperative day 0 or 1. Perioperative stroke was associated with a 3-fold increase in 30-day all-cause mortality [3.36, (1.77 to 6.36)] and an increased median surgical length of stay from 6 (95% CI, 2 to 28) to 13 (95% CI, 3 to 43) days (P < 0.001, WMWodds 2.5, 95% CI, 2.0 to 3.2) in a matched-cohort assessment. CONCLUSION:Perioperative stroke is an important source of morbidity and mortality, as reflected by significant increases in median surgical length of stay and all-cause 30-day mortality. The independent predictors of stroke that we have identified in this population are not readily modifiable and the majority of strokes occurred after postoperative day 1. Additional studies are required to identify potentially modifiable intraoperative or postoperative risk factors of perioperative stroke.

Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia in pigs

BackgroundThe mechanism of isoflurane-induced cerebral hyperemia is poorly understood. Data from studies in vitro suggest that volatile anesthetics release a vasodilator prostanold. We hypothesized that prostanoids and nitric oxide (NO) are mediators of this response in vivo. If true, inhibition of cyclooxygenase by indomethacln (5 mg/kg intravenously) or of nitric oxide synthase by N®-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg intravenously) should attenuate isoflurane-induced hyperemia. Any response to L-NAME occurring via nitric oxide should be competitively reversed by L-arginine. MethodsThe cerebral blood flow (microsphere) response to 1 MAC isofiurane was tested at three time points (0, 90, and 180 min) in pentobarbltal-anesthetized pigs. Isofiurane challenges were separated by 60-min periods of continuous intravenous pentobarbital alone. Control animals (n = 7) received no additional pharmacologlc intervention. Experimental animals were randomized to receive L-NAME before the second and indomethacin before the third isofiurane challenge (n = 7); L-NAME before the second and L-arginine (400 mg/kg intravenously) before the third isofiurane challenge (n = 9); or indomethacin before the second and L-NAME before the third isofiurane challenge (n = 8). ResultsIn control animals, isofiurane reproducibly increased cerebral blood flow (whole brain; 113 ± 18%, 120 ± 18%, and 103 ± 19% increase above baseline at each time point, respectively). Both indomethacin and L-NAME attenuated (10 ± 10% and 52 ± 11% increase, respectively) the hyperemic response to isofiurane. The effect of L-NAME was reversed by L-arginine. ConclusionsWe conclude that both prostanoids and nitric oxide contribute to isoflurane-induced hyperemia. We are unable to determine from our data what, if any, interaction exists between these two mechanisms.

Capnography facilitates tight control of ventilation during transport

OBJECTIVE We tested the hypothesis that Paco2 would be more tightly controlled if end-tidal CO2 monitoring was used during hand ventilation for transport of intubated patients. DESIGN Randomized, prospective analysis of the no-monitor and monitor-blind groups (the monitor was on the bed during transport but only the investigator was aware of the end-tidal CO2 values). Nonrandomized, prospective analysis of the monitor group (ventilation controlled using end-tidal CO2 value from monitor). SETTING University hospital operating room and intensive care unit (ICU). PATIENTS Fifty intubated patients who were transported from the operating room to the ICU or from the ICU to the neuroradiology suite were assigned randomly to one of two groups: a) no-monitor group (n = 25); and b) monitor-blind group (n = 25). An additional group (monitor group, n = 10) was subsequently added to the study. INTERVENTIONS Capnography was instituted in all patients in a blocked fashion. MEASUREMENTS AND MAIN RESULTS Arterial blood gases and end-tidal CO2 values were measured before and after transport. When comparing overall group data, pre- and post-Paco2 values were similar: monitor 39 +/- 2 vs. 41 +/- 2 torr (5.2 +/- 0.3 vs. 5.5 +/- 0.3 no-monitor 39 +/- 1 vs. 37 +/- torr (5.2 +/- 0.1 vs. 5.0 +/- 0.1 kPa). However, when comparing Paco2 values for individual patients, we found that there was significantly greater variability for Paco2 after transport when end-tidal CO2 was not used for control of ventilation during transport. CONCLUSIONS These data do not support routine monitoring of end-tidal CO2 during short transport times in adult patients requiring mechanical ventilation. However, the monitor may prevent morbidity in patients requiring tight control of Paco2.

Perioperative care of patients at high risk for stroke during or after non-cardiac, non-neurologic surgery: Consensus statement from the society for neuroscience in anesthesiology and critical care

This document is supported by the American Society of Anesthesiologists.** Perioperative stroke can be a catastrophic outcome for surgical patients and is associated with increased morbidity and mortality. This consensus statement from the Society for Neuroscience in Anesthesiology and Critical Care provides evidence-based recommendations and opinions regarding the preoperative, intraoperative, and postoperative care of patients at high risk for the complication.

Nitric oxide synthase inhibition with NG-mono-methyl-L-arginine reversibly decreases cerebral blood flow in piglets

ObjectiveWe tested the hypothesis that, in piglets, the intravenous administration of the reversible inhibitor of nitric oxide synthase, NG-mono-methyl-L-arginine, decreases cerebral blood flow via a mechanism unrelated to cerebral oxygen consumption. DesignProspective, randomized, controlled animal study. SettingAnimal laboratory at a university. SubjectsPentobarbital-anesthetized piglets (1 to 2 wks of age; 2.6 to 4.0 kg). InterventionsPiglets were treated with either 50 mg of NG-mono-methyl-L-arginine, 100 mg of NG-mono-methyl-L-arginine, or an equal volume of saline by intravenous infusion over 10 mins. Measurements and Main ResultsMean arterial pressure increased after NG-mono-methyl-L-arginine (50 mg dose: 84 ± 6 to 100 ± 7 mm Hg; 100 mg dose: 82 ± 4 to 107 ± 4 mm Hg; p < .001). Forebrain blood flow (microspheres) decreased (37 ± 2 to 30 ± 2 mL/min/100 g; p < .05) and cerebrovascular resistance increased (2.1 ± 0.2 to 3.5 ± 0.3 mm Hg/mL/min/100 g;p < .05) only after 100 mg of NG-mono-methyl-L-arginine. Neurohypophysis blood flow decreased to 56 ± 9% of the control value, while forebrain blood flow decreased only to 81 ± 4% of the control value after 100 mg of NG-mono-methyl-L-arginine administration. Blood flow returned to control values by 30 mins after infusion. NG-mono-methyl-L-arginine administration had no effect on cerebral oxygen consumption at either dose. Intravenous administration of L-arginine (300 mg) immediately after the infusion of 100 mg of NG-mono-methyl-L-arginine was associated with prompt (by 3 mins) recovery of blood flow to all brain regions that were affected by NG-mono-methyl-L-arginine. ConclusionsThese data suggest that nitric oxide and/or a nitric oxide-containing substance is an important mediator of cerebrovascular tone in piglets, acting via a mechanism unrelated to altering cerebral oxygen consumption. (Crit Care Med 1994; 22:384–392)

Role of Oxygen Free Radicals and Lipid Peroxidation in Cerebral Reperfusion Injury

Publisher Summary This chapter discusses the known pathophysiology of reperfusion injury and outlines some current areas of research that attempt to therapeutically minimize cerebral ischemia and reperfusion injury. There are several possible mechanisms for free radical formation during ischemia and reperfusion. In the absence of oxygen to serve as a terminal electron acceptor, the electron transport chain within mitochondria becomes significantly reduced. In this reduced state oxygen radical formation may result, particularly when oxygen is resupplied. Furthermore, during ischemia the release of excitatory amino acids can stimulate N -methyl- D-aspartate (NMDA) receptors within brain to produce nitric oxide (NO). NO with its unpaired electron is able to initiate free radical chain reactions in the presence of superoxide anion. Cerebral ischemia is associated with the rapid failure of adenosine triphosphate (ATP)-dependent ionic pumps. In an ATP-deficient environment, phospholipase A may also cause the breakdown of phospholipid in cell membranes. As a result, ischemia produces a rapid increase in free fatty acids. The concentrations of fatty acids and arachidonic acid correlate with the duration of ischemia. During ischemia, in addition to the rapid increase in arachidonic acid, there is also an increase in interstitial adenosine and hypoxanthine. Lipid peroxidation appears to be a major mechanism by which radicals produce brain injury. Because of the high concentration of polyunsaturated fats in brain, this organ may be particularly susceptible to insult. Several endogenous free radical scavengers or antioxidants have been tested for their efficacy in reducing neurological, biochemical, metabolic, or histological injury from cerebral ischemia. α -Tocopherol, an endogenous antioxidant, reduces lipid peroxidation when administered prior to ischemia. Deferoxamine, an iron-chelating agent, presumably acts to decrease the amount of free iron available during reperfusion for hydroxyl radical formation. Superoxide dismutase (SOD) and catalase are endogenous free radical scavengers that may act to scavenge tonically produced free radicals under normal conditions.

A cholinergic agonist induces cerebral hyperemia in isoflurane- but not pentobarbital-anesthetized dogs

We tested whether the cerebral blood flow (CBF) response to the cholinergic agonist oxotremorine (OXO) is affected by the choice of anesthetics in dogs. We studied two anesthetics, pentobarbital and isoflurane, which produce similar levels of cerebral metabolic depression but have opposing effects on CBF. We also tested the contribution of nitric oxide (NO, or a NO-containing compound) in mediating the CBF response to OXO by determining whether NO synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) would attenuate OXO-induced hyperemia in both anesthetic groups. CBF (microspheres) was measured before and after OXO administration (50 micrograms.kg-1.min-1 intravenously [i.v.] for 10 min). Animals were divided randomly to receive OXO alone (n = 10) or L-NAME (40 mg/kg i.v.) followed by OXO (n = 10). Within each group, half of the animals received pentobarbital anesthesia (30 mg/kg i.v.) and half received isoflurane (1.4% end-tidal). In pentobarbital-anesthetized animals OXO produced no change in blood flow to cerebrum, caudate, diencephalon, neurohypophysis, or cerebellum in the absence (e.g., cerebrum 37 +/- 2 vs 42 +/- 5 mL/min/100 g) or presence of L-NAME (e.g., cerebrum, 29 +/- 4 vs 30 +/- 3 mL.min-1 x 100 g-1). In isoflurane-anesthetized animals, however, blood flow to forebrain regions increased after OXO (e.g., cerebrum 108 +/- 10 vs 232 +/- 15 mL.min-1 x 100 g-1; P < 0.05) without alteration in oxygen consumption in cerebrum (CMRO2) or blood flow to hindbrain regions. In isoflurane-anesthetized animals, L-NAME decreased baseline blood flow to cerebrum, caudate, diencephalon, cerebellum, and neurohypophysis (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)