Physiologic Effects of Xenon in Xenon-CT Cerebral Blood Flow Studies on Comatose Patients.

Despite more than 30 years of clinical use, questions remain about the safety of xenon gas in Xenon-CT cerebral blood flow (XeCTCBF) studies. In particular, xenon's effect on brain oxygen (PbtO2) in comatose patients is not well defined. Our objective was to assess the effect of a 4.5-min inhalation of 28 % stable xenon on several physiologic variables, including intracranial pressure (ICP), cerebral perfusion pressure (CPP), and PbtO2 in comatose patients (Glasgow Coma Scale [GCS] ≤ 8). Thirty-seven comatose patients who underwent 73 XeCTCBF studies were identified retrospectively from a prospective observational database. Changes in MAP, HR, SaO2, EtCO2, ICP, CPP, and PbtO2 measured at the start of xenon administration and every minute for 5 min thereafter were assessed. The maximum change in each variable also was determined for each scan to tabulate clinically relevant changes. Statistically, but not clinically significant changes in MAP, HR, and EtCO2 were seen. Xenon had no effect on ICP, and a small, but clinically insignificant decrease in CPP and PbtO2, was observed. There was a varied response to xenon in most measured variables. Clinically significant changes in each were infrequent, and readily reversed with the cessation of the gas. We conclude that xenon does not appear to have a clinically significant effect on ICP, CPP, and PbtO2 and so appears safe to evaluate cerebral blood flow in comatose patients.

Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension.

BACKGROUND: The impact of osmotic therapies on brain oxygen has not been extensively studied in humans. We examined the effects on brain tissue oxygen tension (PbtO(2)) of mannitol and hypertonic saline (HTS) in patients with severe traumatic brain injury (TBI) and refractory intracranial hypertension. METHODS: 12 consecutive patients with severe TBI who underwent intracranial pressure (ICP) and PbtO(2) monitoring were studied. Patients were treated with mannitol (25%, 0.75 g/kg) for episodes of elevated ICP (>20 mm Hg) or HTS (7.5%, 250 ml) if ICP was not controlled with mannitol. PbtO(2), ICP, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure and cardiac output were monitored continuously. RESULTS: 42 episodes of intracranial hypertension, treated with mannitol (n = 28 boluses) or HTS (n = 14 boluses), were analysed. HTS treatment was associated with an increase in PbtO(2) (from baseline 28.3 (13.8) mm Hg to 34.9 (18.2) mm Hg at 30 min, 37.0 (17.6) mm Hg at 60 min and 41.4 (17.7) mm Hg at 120 min; all p<0.01) while mannitol did not affect PbtO(2) (baseline 30.4 (11.4) vs 28.7 (13.5) vs 28.4 (10.6) vs 27.5 (9.9) mm Hg; all p>0.1). Compared with mannitol, HTS was associated with lower ICP and higher CPP and cardiac output. CONCLUSIONS: In patients with severe TBI and elevated ICP refractory to previous mannitol treatment, 7.5% hypertonic saline administered as second tier therapy is associated with a significant increase in brain oxygenation, and improved cerebral and systemic haemodynamics.

Transcranial Doppler ultrasonography with induction of anesthesia and neuromuscular blockade in surgical patients.

STUDY OBJECTIVES: To evaluate the cerebral vascular effects of cis-atracurium and rocuronium given after thiopental induction of anesthesia. DESIGN: Randomized, single-blinded study. SETTING: University-affiliated hospital. PATIENTS: 39 adult ASA physical status I and II patients undergoing nonintracranial procedures. INTERVENTIONS: Patients received intravenously (IV), either saline placebo, cis-atracurium, or rocuronium after induction of general anesthesia with thiopental sodium. MEASUREMENTS: The right middle cerebral artery was insonated using a pulsed-wave range-gated transcranial Doppler, and data were recorded at preinduction, immediately postinduction, at injection of the study drug, and at 15-second intervals for 3 minutes thereafter. The variables recorded for each subject included the systolic, diastolic, and mean flow velocity, as well as pulsality index, systolic, diastolic, and mean arterial blood pressure (MAP), and end-tidal carbon dioxide concentration. MAIN RESULTS: No significant differences between the groups were present in the postanesthetic induction maximal or minimal mean flow velocity. CONCLUSIONS: cis-Atracurium and rocuronium, administered after thiopental, do not produce clinically relevant changes in cerebral blood flow velocity.

Acute care crisis simulation for jury education.

A major impediment to appropriate adjudication in medical malpractice cases is the large difference in knowledge and background of the expert witness compared to judges, other litigants and juries. Such disparities make it plausible for an expert witness to support an issue, even in defiance of common sense. The most basic understanding of the atmosphere and practices surrounding critical events and the routine procedures, techniques and equipment which are employed in critical situations is absent. (McAbee GN: Improper expert medical testimony: existing and proposed mechanisms of oversight. Journal of Legal Medicine 19: 257-272, 1998).

Opioid neurotoxicity: role of neurotransmitter systems.

We hypothesized that blockade of synthesis or release of several categories of neurotransmitters would ameliorate opioid neurotoxicity. Rats were randomly assigned to one of six groups in two sequential protocols: vesamicol (VES, n = 10), alpha-fluoromethylhistidine (FMH, n = 10), reserpine (RES, n = 10), BW1003C87 (BW, n = 7), lamotrigine (LAM, n = 10), or one of two control groups (CON, n = 19). Physiologically controlled rats received fentanyl (fen) i.v., loading dose 800 micrograms kg-1 followed by maintenance dose 32 micrograms kg-1 min-1 for 2 h. Drug dosing: CON, isovolemic (between rats) 0.9% saline i.v.; BW, 20 mg kg-1 i.v. 15 min pre-fen; LAM, 16 mg kg-1 i.v. 30 min pre-fen; VES, 2.5 mg kg-1 i.p. 60 min and 30 min pre-fen then infused 3.75 mg kg-1 during fen; FMH, 20 mg kg-1 i.p. 2 h pre-fen; RES, 0.75 mg kg-1 i.p. 18 h pre-fen. Seven days later all rats underwent cerebral perfusion fixation, followed by histologic grading (0-5, 0 = normal). Pathological data was analyzed by Wilcoxen's Signed rank test (two-tailed) for pathologic scores summated across all brain areas (overall severity score) and for scores of areas previously associated with opioid neurotoxicity. Compared to CON, overall severity was decreased by RES (p = 0.05) with an effect suggested by VES (p = 0.10). Compared to CON, lesions were decreased: (a) in the amygdala with VES (p = 0.03) and RES (p = 0.05) with a trend suggested by BW (p = 0.06); (b) in the subiculum by VES (p = 0.02) and RES (p = 0.008) with a trend suggested by FMH (p = 0.06); and (c) in the entorhinal cortex by VES (p = 0.004) and RES (p = 0.008) with a trend suggested by FMH (p = 0.07). The data indicate that brain acetylcholine and catecholamines contribute to opioid neurotoxicity, and suggest a possible role of glutamate and histamine in opioid neurotoxicity.

Phenytoin, midazolam, and naloxone protect against fentanyl-induced brain damage in rats.

UNLABELLED: In previous studies, large-dose fentanyl produced electrographic seizure activity and histologically evident brain damage. We assessed whether fentanyl-induced brain damage is attenuated by using anticonvulsant drugs. Using halothane/nitrous oxide anesthesia, 40 Sprague-Dawley rats underwent tracheal intubation, arterial and venous cannulation, and insertion of biparietal electroencephalogram electrodes and a rectal temperature probe. Halothane was discontinued. The dose of IV fentanyl shown previously to cause maximal brain damage was given to all animals and N(2)O was discontinued. Control rats were given fentanyl only. Rats in the three study groups also received midazolam, phenytoin, or N(2)O/naloxone. After characteristic seizure activity began with fentanyl loading the study drug was started. After a 2-h infusion, wounds were closed, and animals recovered overnight and underwent cerebral perfusion-fixation. Neuropathologic alterations were ranked on a scale of 0-5 for both neuronal death (0 = normal, 5 = more than 75% neuronal death) and for malacia. Significantly fewer rats in the N(2)O/Naloxone, Phenytoin, and Midazolam Groups sustained any brain damage compared with controls. Protection against opioid neurotoxicity is achieved with midazolam, naloxone, and phenytoin. If opioid neurotoxicity is clinically relevant, a small change in anesthetic practice might reduce any potential neurologic morbidity. IMPLICATIONS: Narcotics in large doses can cause brain damage in rats. This brain damage is attenuated by a narcotic antagonist, a sedative, and an antiepileptic drug.

Anaesthetic complications of acromegaly.

The anaesthetic risks of acromegaly include difficulties in airway management, hypertension, and cardiac, gastrointestinal and renal problems. To estimate the incidence of major complications in this rare group of patients, we reviewed 28 patients with acromegaly who had pituitary tumour excision over a 10-yr period. Each patient was matched for age, weight and sex to a non-acromegalic patient undergoing transsphenoidal pituitary surgery. Acromegalic patients received significantly more fentanyl and midazolam and less thiopental and succinylcholine than controls (all P < 0.05). Mean arterial pressure (baseline, minimal and maximal values) was higher in acromegalic patients than in controls. There was no difference between groups in the use of vasoactive drugs. PaO2, FIO2 and PaCO2 were similar in both groups. Arterial pH was significantly lower (P = 0.015), blood glucose was higher (P < 0.001) and fluid intake minus output was higher (P = 0.04) in acromegalic patients than in controls. Airway difficulty and tongue enlargement were encountered more often in acromegalic patients (P = 0.002 and P = 0.001, respectively). Our data confirm that in acromegalic patients: airway difficulties occurred more frequently; severe haemodynamic instability did not typically occur during surgery for acromegaly; pulmonary gas exchange was not altered during operation; glucose intolerance may be an intraoperative problem; and fluid regulation may be altered.

The value of acute care simulation.

Simulation of crises has long been a component of training in the aviation and nuclear industries. This technology has been successfully transferred and adapted to acute care medicine and allied health care. In this article, we describe the capabilities and uses of human acute care simulation at West Virginia University Hospital.

Opioid neurotoxicity: fentanyl-induced exacerbation of cerebral ischemia in rats.

We tested the hypothesis that fentanyl would worsen ischemia-induced brain damage. In two sequential protocols forty rats were physiologically monitored and controlled. In protocol 1, rats were randomized (n=10/group) to 30 min of control (N2O plus 0.4% halothane), low dose fentanyl (loading dose [LD] 50 micrograms kg-1, maintenance dose [MD] 2 micrograms kg-1 min-1), or high-dose fentanyl (LD 800 micrograms kg-1, MD 32 micrograms kg-1 min-1). After 15 min of fentanyl or sham infusion trimethaphan 0.5 mg was given i.v. and 3 min later bilateral carotid artery occlusion and blood withdrawal-induced hypotension were maintained for 12 min. At 18 h postischemia rats underwent cerebral perfusion fixation. Brain areas were graded from 0 (normal) to 5. In addition to analysis of specific regions, neuropathologic scores were also summated over all brain regions and analyzed to compute a summed neuropathologic score. In protocol 2, five control and five high-dose fentanyl rats were treated identically except that post-ischemic oxygenation was maintained for 6 h and cerebral perfusion-fixation was performed 6 h post-ischemia. Only the caudate/putamen was examined in protocol 2. Fentanyl worsened lesions in both fentanyl groups' summed neuropathologic scores (P=0.002) in protocol 1 and specifically, in the caudate/putamen (P<0.01) in both protocols. Fentanyl in both high and low doses can exacerbate incomplete forebrain ischemia in rats.

Correlation of transcranial Doppler sonography mean flow velocity with cerebral blood flow in patients with intracranial pathology.

Several studies suggest that relative changes in cerebral blood flow (CBF) may be assessed via transcranial Doppler sonography (TCD). The present study investigates the correlation between changes in TCD-mean flow velocity (Vm) and changes in CBF in patients with a variety of types of intracranial pathology undergoing cerebrovascular reactivity tests. After informed consent was obtained, 32 patients presenting with stenoses of brain-supplying arteries (n = 13), cerebral vascular malformations (n = 6), surgical decompression for subarachnoid hemorrhage (n = 2), brain edema after closed head injury (n = 8), or hepatic encephalopathy (n = 3) were studied. The patients were divided into two groups for different reactivity tests. Patients in group 1 (awake or sedated, n = 18) received a 1-g dose of acetazolamide intravenously. In group 2 (n = 14), mechanical ventilation was adjusted to produce a 20% decrease in arterial CO2 tension compared with baseline. Regional CBF was measured using xenon-enhanced computed tomography (Xe-CT). Xe-CT scans at the levels of the basal ganglia and the lateral ventricles were performed during a 4.5-min xenon wash-in period. Bilateral flow velocity was measured in the middle cerebral artery using a 2-MHz pulsed TCD system. Mean arterial blood pressure, heart rate, and end-tidal CO2 were continuously recorded during the procedure. After baseline measurements and either alteration of CO2 or application of acetazolamide, the cerebrovascular reactivity was assessed at 20 min by a second measurement of CBF, TCD, and all other physiologic variables. The correlation coefficient for relative changes of MCA territory CBF versus Vm and for the overall population was r = 0.82. In groups 1 and 2, the r values were 0.39 and 0.5, respectively. Correlation coefficients did not exceed r = 0.4 in any subgroup-classification based on diagnosis. The close correlation between changes in CBF and Vm (r = 0.82) in patients with heterogeneous intracranial pathology seems to show that TCD is a measure of CBF. However, in groups 1 and 2 and in subgroups formed of patients classified according to diagnoses, data dispersion suggests that the actual correlation is weaker. Relation of changes in Vm to those in CBF may depend on the underlying diagnosis. These data indicate that the correlation between Vm and CBF may vary with intracranial pathology.

Anesthetic implications of epilepsy, status epilepticus, and epilepsy surgery.

Epilepsy is a clinical paroxysmal disorder of recurring seizures, excluding alcohol or drug withdrawal seizures or such recurring exogenous events as repeated insulin-induced hypoglycemia. Epilepsy has a profound impact on each individual diagnosed with this disease. Seizures have been and are thought to arise as a result of abnormalities in (a) neural circuits, (b) excitation/inhibition balance, (c) potassium, and (d) genetic abnormalities. Therapy for epilepsy is either medical, entailing the use of a variety of antiepileptic drugs, or surgical. An urgent approach to seizure control is indicated when status epilepticus occurs. When all standard therapy fails, general anesthesia can be used to control status epilepticus. Surgery is an option in the treatment of epilepsy and requires extensive preoperative evaluation. The primary concerns for the neuroanesthesiologist anesthetizing the patient with epilepsy are the capacity of anesthetics to modulate or potentiate seizure activity and the interaction of anesthetic drugs with antiepileptic drugs. Proconvulsant and anticonvulsant properties have been reported for nearly every anesthetic. If seizure spikes are to be evoked during seizure surgery, then light anesthesia with a proconvulsant anesthetic is used. Conscious analgesia can be used for awake seizure surgery. However, if electrocorticography is not planned, then a general anticonvulsant anesthetic maintenance regimen is used. The latter technique also may be useful in patients whose anesthetic management is complicated by an incidental history of epilepsy.

Electrographic tachyphylaxis to etomidate and ketamine used for refractory status epilepticus controlled with isoflurane.

Etomidate and ketamine controlled seizures but acute tachyphylaxis occurred. Isoflurane was then used to control seizures.

Opioid neurotoxicity: fentanyl dose-response effects in rats.

Opioids, when administered in large doses, produce brain damage, primarily in the limbic system and association areas in rats. This investigation examined the relationship between opioid dose and severity and frequency of brain damage in rats. Forty male Sprague-Dawley rats were anesthetized with halothane/N2O and underwent tracheal intubation, mechanical ventilation, arterial/venous cannulation, and insertion of a rectal temperature probe and biparietal electroencephalogram electrodes. After surgery, halothane was discontinued and O2/N2O 30%/70% was administered for 1 h. Rats were then randomly assigned to one of eight groups. The control group received a loading dose (LD) of 4 mL/kg of 0.9% normal saline solution (NSS) and a maintenance dose (MD) of 4 mL.kg-1.h-1 NSS. The other groups were given fentanyl lypophilized and reconstituted in NSS with the LD ranging from 50 to 3200 micrograms/kg and the MD from 2 to 128 micrograms.kg-1.min-1. After 2 h of fentanyl or NSS infusion; all rats received 100% O2 and, when alert, their tracheas were extubated; after 7 days the rats underwent cerebral perfusion fixation, followed by light microscopic evaluation. Histopathologic lesions (primarily eosinophilic neuron degeneration) were subjectively graded by a pathologist unaware of the experimental treatment; the grades were based on the percentage of dead neurons. There were no lesions observed in the brain areas in any of the control or 200-8 (LD, microgram/kg; MD, microgram.kg-1.min-1) groups. Eleven of 20 rats in the 400-16, 800-32, 1600-64, and 3200-18 groups showed evidence of brain damage primarily in limbic system structures and association areas (P < 0.05). Our data confirm that fentanyl produces limbic system brain damage in rats, and that the damage occurs over a broad range of doses.

Opioid neurotoxicity: neuropathologic effects in rats of different fentanyl congeners and the effects of hexamethonium-induced normotension.

We tested the hypotheses that convulsant doses of opioids would produce limbic system damage exacerbated by hexamethonium. Ventilated paralyzed rats received intravenous (IV) isovolumic infusion of fentanyl loading dose (LD) 1000 micrograms/kg, maintenance dose (MD) 40 micrograms.kg-1.min-1 (n = 10), sufentanil LD 400 micrograms/kg, MD 13.3 micrograms.kg-1.min-1 (n = 10), alfentanil LD 1500 micrograms/kg, MD 150 micrograms.kg-1.min-1 (n = 10), or 0.9% saline control LD 4 mliter/kg, MD 4 mliter.kg-1.h-1 (n = 10), with O2/N2 30%/70% during opioid infusion and O2/N2O in controls during saline infusion. Hexamethonium (LD 20 mg/kg, MD 40-120 mg.kg-1.h-1) was given IV during opioid infusion to half of the rats. Cerebral perfusion-fixation with formalin was performed 24 h later, followed by histopathologic assessment. None of the control rats showed any histologic abnormalities. Overall summed neuropathologic severity was worse in opioid treated groups (P = 0.01). Lesions occurred primarily in cortical regions and limbic system structures. When arterial blood pressure was controlled to a lower level with hexamethonium (147 vs 100 mm Hg), rats had less severe lesions (P = 0.02). These data indicate that fentanyl, sufentanil, and alfentanil all can produce histopathologic evidence of brain injury in rats mitigated by hexamethonium.

Suspended animation for delayed resuscitation.

Suspended animation is defined as the therapeutic induction of a state of tolerance to temporary complete systemic ischemia, i.w., protection-preservation of the whole organism during prolonged circulatory arrest ( > or = 1 hr), followed by resuscitation to survival without brain damage. The objectives of suspended animation include: a) helping to save victims of temporarily uncontrollable (internal) traumatic (e.g., combat casualties) or nontraumatic (e.g., ruptured aortic aneurysm) exsanguination, without severe brain trauma, by enabling evacuation and resuscitative surgery during circulatory arrest, followed by delayed resuscitation; b) helping to save some nontraumatic cases of sudden death, seemingly unresuscitable before definite repair; and c) enabling selected (elective) surgical procedures to be performed which are only feasible during a state of no blood flow. In the discussion session, investigators with suspended animation-relevant research interests brainstorm on present knowledge, future research potentials, and the advisability of a major research effort concerning this subject. The following topics are addressed: the epidemiologic facts of sudden death in combat casualties, which require a totally new resuscitative approach; the limits and potentials of reanimation research; complete reversibility of circulatory arrest of 1 hr in dogs under profound hypothermia ( < 10 degrees C), induced and reversed by portable cardiopulmonary bypass; the need for a still elusive pharmacologic or chemical induction of suspended animation in the field; asanguinous profound hypothermic low-flow with cardiopulmonary bypass; electric anesthesia; opiate therapy; lessons learned by hypoxia tolerant vertebrate animals, hibernators, and freeze-tolerant animals (cryobiology); myocardial preservation during open-heart surgery; organ preservation for transplantation; and reperfusion-reoxygenation injury in vital organs, including the roles of nitric oxide and free radicals; and how cells (particularly cerebral neurons) die after transient prolonged ischemia and reperfusion. The majority of authors believe that seeking a breakthrough in suspended animation is not utopian, that ongoing communication between relevant research groups is indicated, and that a coordinated multicenter research effort, basic and applied, on suspended animation is justified.

Transcranial Doppler ultrasonography in neurosurgery: effects of intracranial tumour on right middle cerebral artery flow velocity during induction of anaesthesia.

The right middle cerebral artery flow velocity (MCAFV) was measured by transcranial Doppler ultrasonography in neurosurgical patients with and without intracranial tumours during anaesthetic induction and endotracheal intubation. With institutional and patient consent, 20 non-tumour and 85 tumour-bearing neurosurgical patients were enlisted. The right middle cerebral artery was insonated with a pulsed-wave range-gated transcranial Doppler at 2 MHz, and MCAFV was recorded via a video graphics printer. The mean MCAFV, pulsatility index, use of anaesthetic drugs, heart rate, mean arterial pressure, and endtidal CO2 were recorded on preinduction, postinduction, intubation, and 90 to 180 s postintubation. There was no demographic, systemic haemodynamic, or anaesthetic difference between groups except for a predominance of women in the tumour group. In all patients, mean arterial pressure and MCAFV demonstrated with time a significant decrease with anaesthetic induction, increase with endotracheal intubation, and decrease post intubation. The right MCAFV was significantly higher in both tumour and right-sided tumour patients compared to non-tumour patients. There was no difference in left-sided tumour patients compared to non-tumour patients. These data indicate that intracranial tumours have cerebrovascular effects, causing either hyperaemia or vasoconstriction, and that the effects of anaesthetic induction and intubation agree with previously reported effects on cerebral blood flow and intracranial pressure.