Dexmedetomidine-mediated neuroprotection against sevoflurane-induced neurotoxicity extends to several brain regions in neonatal rats.

BACKGROUND: Exposure of infant animals to clinically used anaesthetics is associated with acute structural brain abnormalities and development functional alterations. The α 2 -adrenoceptor agonist dexmedetomidine (DEX) induces sedation, analgesia, and provides neuroprotection in experimental brain injury models. However, it is unknown whether DEX also affords protection in the developing brain against anaesthesia using sevoflurane (SEVO), which is commonly used in paediatric anaesthesia. METHODS: Infant rats were exposed on postnatal day seven for six h to 2.5% SEVO and were given i.p. injections of saline or DEX (1-50 µg kg -1 ) three times during the exposure. Level of anaesthesia, respiratory rates, and arterial blood gasses were assessed for each animal. Apoptosis was determined in brain slices immunostained for activated caspase-3 (AC-3) using a computerised approach. RESULTS: SEVO alone induced a surgical plane of anaesthesia, and all animals survived the study. SEVO induced an approximately 10-fold increase in AC-3 positive cells in several cortical and subcortical brain regions compared with untreated control animals. Co-administration of DEX 1 µg kg -1 with SEVO significantly reduced apoptosis in all brain areas, affording the highest protection in the thalamus (84% reduction) and lowest in the hippocampus and cortical areas (∼50% reduction). DEX 5-25 µg kg -1 plus SEVO dose-dependently increased infant rat mortality. CONCLUSIONS: SEVO anaesthesia induced widespread apoptosis in infant rat brain. Co-administration of DEX (1 µg kg -1 ) provided significant protection, whereas DEX (5 µg kg -1 or higher) plus SEVO increased mortality. Our findings suggest that DEX could be an attractive therapeutic for future studies investigating its neuroprotective potential in a translational animal model.

Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain.

BACKGROUND: Retrospective clinical studies suggest there is a risk for neurodevelopmental impairment following early childhood exposure to anaesthesia. In the developing animal brain, including those of non-human primates (NHPs), anaesthetics induce apoptotic cell death. We previously reported that a 5 h isoflurane (ISO) exposure in infant NHPs increases apoptosis 13-fold compared with control animals. However, the majority of paediatric surgeries requiring anaesthesia are of shorter durations. We examined whether 3 h ISO exposure similarly increases neuroapoptosis in the NHP developing brain. METHODS: Six-day-old NHP infants ( Macaca mulatta ) were exposed to 3 h of a surgical plane of ISO ( n =6) or to room air ( n =5). Following exposure, NHP brains were screened for neuronal and oligodendrocyte apoptosis using activated caspase-3 immunolabelling and unbiased stereology. RESULTS: ISO treatment increased apoptosis (neurones + oligodendrocyte) to greater than four times that in the control group [mean density of apoptotic profiles: 57 (SD 22) mm -3 vs 14 (SD 5.2) mm -3 , respectively]. Oligodendrocyte apoptosis was evenly distributed throughout the white matter whereas neuroapoptosis occurred primarily in the cortex (all regions), caudate, putamen and thalamus. CONCLUSIONS: A 3 h exposure to ISO is sufficient to induce widespread neurotoxicity in the developing primate brain. These results are relevant for clinical medicine, as many surgical and diagnostic procedures in children require anaesthesia durations similar to those modelled here. Further research is necessary to identify long-term neurobehavioural consequences of 3 h ISO exposure.

Predictors of difficult videolaryngoscopy with GlideScope® or C-MAC® with D-blade: secondary analysis from a large comparative videolaryngoscopy trial.

BACKGROUND: Tracheal intubation using acute-angle videolaryngoscopy achieves high success rates, but is not without difficulty. We aimed to determine predictors of 'difficult videolaryngoscopy'. METHODS: We performed a secondary analysis of a data set (n=1100) gathered from a multicentre prospective randomized controlled trial of patients for whom difficult direct laryngoscopy was anticipated and who were intubated with one of two videolaryngoscopy devices (GlideScope(®) or C-MAC(®) with D-blade). 'Difficult videolaryngoscopy' was defined as 'first intubation time >60 s' or 'first attempt intubation failure'. A multivariate logistic regression model along with stepwise model selection techniques was performed to determine independent predictors of difficult videolaryngoscopy. RESULTS: Of 1100 patients, 301 were identified as difficult videolaryngoscopies. By univariate analysis, head and neck position, provider, type of surgery, and mouth opening were associated with difficult videolaryngoscopy (P<0.05). According to the multivariate logistic regression model, characteristics associated with greater risk for difficult videolaryngoscopy were as follows: (i) head and neck position of 'supine sniffing' vs 'supine neutral' {odds ratio (OR) 1.63, 95% confidence interval (CI) [1.14, 2.31]}; (ii) undergoing otolaryngologic or cardiac surgery vs general surgery (OR 1.89, 95% CI [1.19, 3.01] and OR 6.13, 95% CI [1.85, 20.37], respectively); (iii) intubation performed by an attending anaesthestist vs a supervised resident (OR 1.83, 95% CI [1.14, 2.92]); and (iv) small mouth opening (OR 1.18, 95% CI [1.02, 1.36]). CONCLUSION: This secondary analysis of an existing data set indicates four covariates associated with difficult acute-angle videolaryngoscopy, of which patient position and provider level are modifiable.

[Ischemic complications in neurosurgery: use of calcium antagonists]. / Ischämische Komplikationen in der Neurochirurgie: Einsatz von Kalziumantagonisten.

Dysregulation of the intracellular calcium concentration is thought to play a key role in the so-called ischemic cascade, as well as for the development of cerebral vasospasm after subarachnoid haemorrhaging (SAH). Therefore, the prophylactic/therapeutic administration of cerebral calcium channel blockers for neurosurgical patients appears to be a compelling idea to prevent ischemic complications. There are abundant data on the efficacy of cerebral calcium antagonists in various animal models of central nervous system pathologies, however, very little clinical evidence exists to justify their use in humans in respective situations. So far there is only evidence for a long-term treatment effect of oral nimodipine in patients suffering from SAH, and this is based essentially on one large controlled clinical trial. Experimental results suggest that blockers of other calcium channel subtypes may be promising for future clinical roles in primary or secondary ischemic brain injury. However, it is also possible that calcium-independent mechanisms play a more important role during the development of the ischemic damage than previously assumed. Currently, there is no clinical evidence to support the prophylactic use of calcium antagonists to prevent ischemic complications in neurosurgical patients without SAH.

Efficacy of vertical infraclavicular plexus block vs. modified axillary plexus block: a prospective, randomized, observer-blinded study.

BACKGROUND: Despite containing severe risks, infraclavicular approaches to the brachial plexus gained increasing popularity. Likewise, the vertical infraclavicular plexus block improved anesthesia compared to the standard axillary approach but contains the risk of pneumothorax. Therefore we modified the standard axillary technique by inserting a proximal directed catheter, referred to as a high axillary plexus block. We prospectively compared quality and onset of neural blockade after vertical infraclavicular plexus block (VIP) and high axillary plexus block (HAP) in two randomized groups (30 patients in each). METHODS: In group VIP the insulated needle was inserted midway between the ventral process of the acromion and the jugular notch. In group HAP, first an axillary needle was placed. Through this a stimulating catheter was inserted in a proximal direction (10-15 cm); correct placement was confirmed by nerve stimulation. All patients received 40 ml ropivacaine 0.75% (300 mg). Discriminating between analgesia and anesthesia, a blinded observer assessed progression of neural blockade every 5 min for 60 min by pin prick. Incomplete blocks were supplemented 60 min after initial injection. RESULTS: All patients in both groups demonstrated sufficient surgical anesthesia. No patient needed systemic supplementation or general anesthesia. However, vertical infraclavicular plexus block indicated superior anesthesia compared to high axillary plexus block, regarding musculocutaneous, axillary and radial nerve, which were completely blocked with a higher success rate and in a shorter time interval (P < 0.05). CONCLUSIONS: While both techniques provide sufficient surgical anesthesia, vertical infraclavicular plexus block demonstrated a partially higher success rate and a faster onset than high axillary plexus block.

Spinal anesthesia in an extremely low birth weight infant.

A case of spinal anesthesia in an extremely low birth weight male infant (body weight of 930 g at time of surgery) is presented. He was born prematurely at a gestational age of 27 weeks because of a placenta tumor and had to undergo inguinal herniotomy at 34 weeks postconceptional age. He had bronchopulmonary dysplasia and oxygen supply was still required because of frequent deterioration of oxygen saturation. Spinal anesthesia was performed successfully without any complications. Relevant aspects concerning the technique and management of spinal anesthesia in preterm infants are discussed.

Pharmacological preconditioning in global cerebral ischemia.

Single dose 3-nitropropionic acid (3-NPA) 24 hr before global ischemia improves neuronal survival in both, neocortex and hippocampus ('chemical preconditioning'). Neuronal survival after transient global ischemia requires new protein synthesis during recovery, especially of those with anti-apoptotic function. Bcl-2-protein is expressed in neurons that survive cerebral ischemia and may parallel the time course of tolerance after ischemic preconditioning. With this study we examined whether differences in bcl-2-protein expression compared to baseline may be involved in the induction of ischemic tolerance using 3-NPA. Male Wistar rats received either a single intraperitoneal (i.p.) dose of 3-NPA (20 mg/kg), and were observed for 3 (n = 4), 12 (n = 5) or 24 hours (n = 5) or the same amount of vehicle and were observed for 24 h (n = 8, controls). Immunohistochemistry allowed to compare the intensity of bcl-2 immunoreactivity at three subsequent time points in hippocampus, dentate gyrus and parietal neocortex with that of control animals. A single dose of 3-NPA caused a significant increase of bcl-2 protein immunoreactivity in hippocampal neurons, i.e. CA 1 (5 out of 5 animals, p = 0.003), CA 3 (5/5, p = 0.003), CA 4 (4/5, p = 0.025), and neocortex (5/5, p = 0.004), in a time dependent manner over a period of 24 hr after injection. Neuronal bcl-2 protein expression in CA 2 and dentate gyrus remained unchanged. The data suggest a possible role of bcl-2-protein in chemical induction of ischemic tolerance using a single subtoxic dose of 3-NPA. Bcl-2-protein expression may be initiated by increased levels of reactive oxygen species (ROS) after 3-NPA administration, as shown by others. Additional bcl-2 protein may then be available to (1) control postischemic ROS burst, (2) protect the mitochondrial membranes, and (3) inhibit pro-apoptotic mechanisms.

[Management of pediatric airway--anatomy, physiology and new developments in clinical practice]. / Der kindliche Atemweg--Anatomische und physiologische Besonderheiten sowie neue Erkenntnisse zum Airway-Management in der klinischen Praxis.

Due to the special features of paediatric anatomy and physiology, the expected and unexpected difficult paediatric airway is one of the major challenges to every anaesthesiologist, paediatrician and emergency physician. During the last years, some new devices have been made available to improve airway management in children and infants, and several studies have advanced our understanding of the risks and benefits of our clinical practice. Certain risk factors for airway related problems during anaesthesia in children having a "cold" have been identified, and there are new aspects of the controversy concerning the use of cuffed endotracheal tube (ETT) in children. New video assisted systems have been introduced for the management of the difficult airway in paediatric patients, and new applications for well-known devices have been suggested, e.g. the laryngeal mask airway (LMA) serving as guidance for fibreoptic intubation. Recent studies have also demonstrated specific problems with the LMA in infants, as well as possible advantages of a new prototype LMA for children, similar to the ProSeal. Furthermore, the following review presents data about the use of the Cuffed Oropharyngeal Airway (COPA) and the Laryngeal Tube (LT) in paediatric patients.

[Paracetamol in childhood. Current state of knowledge and indications for a rational approach to postoperative analgesia]. / Paracetamol im Kindesalter Aktueller Wissensstand und Hinweise für einen rationalen Einsatz zur postoperativen Analgesie.

The administration of paracetamol (in the US known as acetaminophen) to children and infants for postoperative pain after minor surgery is a well established and safe treatment option, if appropriately used. However, if paracetamol is dosed according to traditional recommendations (about 20 mg/kg body weight) frequently a sufficient analgetic effect cannot be achieved immediately after painful interventions. Recently, a higher initial dose (40 mg/kg body weight) was suggested for effective postoperative pain control, which seems especially important for children after ambulatory anesthesia, but may also be associated with certain risks to the patient. Current recommendations also involve appropriate timing and route of administration of paracetamol to be most effective under different clinical circumstances. In contrast, the risk for liver toxicity appears to be very low, if the daily paracetamol dose does not exceed 90 mg/kg body weight in otherwise healthy children, and if specific risk factors of the individual patient are always considered. This review discusses the recent publications on pharmacokinetics and -dynamics, the clinical use and dosing, as well as the risks and benefits of paracetamol for the treatment of postoperative pain in children and infants. Based on this information, specific dosing regimes for the postoperative period are suggested for neonates and infants, as well as for children in different age groups.

Failure to sustain recovery of Na,K-ATPase function is a possible mechanism for striatal neurodegeneration in hypoxic-ischemic newborn piglets.

Hypoxia-ischemia (HI) in the newborn can lead to a variety of sensorimotor abnormalities, including movement and posture disorders. Striatal neurons undergo necrosis after HI in piglets, but mechanisms for this neuronal death are not understood. We tested the hypothesis that Na,K-ATPase is defective in striatum early after HI. Piglets (1 week old) were subjected to 30 min hypoxia (arterial oxygen saturation 30%) and then 7 min of airway occlusion (oxygen saturation 5%), producing asphyxic cardiac arrest. Animals were resuscitated and recovered for 3, 6, 12, and 24 h, respectively. Neuronal necrosis in the striatum is progressive [14]. Na,K-ATPase activity (percent of control) was 60, 98, 51, and 54% at 3, 6, 12, and 24 h after HI, respectively. Intrastriatal differences in enzyme activity were detected histochemically, with the putamen showing greater loss of Na,K-ATPase activity than caudate after 12 h recovery. Immunoblotting showed that the levels of the alpha(3) isoform (localized exclusively to neurons) were 85, 115, 101, and 79% of sham control at 3, 6, 12, and 24 h, respectively. Levels of beta(1), the predominant beta isoform, were similar to alpha(3), while levels of the alpha(1) subunit, the catalytic isoform found in neurons and glia, were 182, 179, 226, and 153% at the same recovery times. We conclude that early inactivation of Na,K-ATPase function participates in the pathogenesis of striatal neuron necrosis, but that loss of enzyme function early after HI is not caused by depletion of composite alpha/beta subunits.

Publications on paediatric anaesthesia: a quantitative analysis of publication activity and international recognition.

A comprehensive compilation of the current international literature on paediatric anaesthesia is lacking. The aim of this study was to identify all articles on clinical practice in paediatric anaesthesia, to name the respective journals, and to assess the publication activity and international recognition of selected countries for a 6-yr period (1993-1998). The search comprised an article-to-article evaluation ('hand search') of 12 peer-reviewed anaesthesia journals, as well as an Internet-based ('SilverPlatter') Medline-search (3,900 medical journals, US National Library of Medicine), both limited to original articles, case reports, reviews and editorials. Selected physical characteristics, for example the number of infants and children aged 0-14 yr old, the number of anaesthetists (specialists) and current impact factors (Science Citation Index) served to assess publication activity and international recognition. During the time period studied, 2259 articles (377/yr) were published on paediatric anaesthesia in 295 medical journals. The articles were primarily written in English (85.1%) and the majority originated from the USA (35.4%) and the UK (12.6%). The largest number of publications (77.7%) appeared in 29 anaesthesia journals, all referenced in Medline, with 46% being published by only five journals. Most authors published in journals of their home country/region. Authors from the UK ranked highest in publication activity, followed by those from Canada, Switzerland, Sweden and Denmark. The highest impact factor was achieved by US and UK authors. We conclude that publications on paediatric anaesthesia are clustered in a small number of journals and are written predominantly by authors from English-speaking countries, who achieved the highest international recognition.

Tolerance-Inducing dose of 3-nitropropionic acid modulates bcl-2 and bax balance in the rat brain: a potential mechanism of chemical preconditioning.

Many studies have reported ischemia protection using various preconditioning techniques, including single dose 3-nitropropionic acid (3-NPA), a mitochondrial toxin. However, the cellular signal transduction cascades resulting in ischemic tolerance and the mechanisms involved in neuronal survival in the tolerant state still remain unclear. The current study investigated the mRNA and protein expression of the antiapoptotic bcl-2 and the proapoptotic bax. two antagonistic members of the bcl-2 gene family, in response to a single dose of 3-NPA, to global cerebral ischemia-reperfusion. and to the combination of both 3-NPA-pretreatment and subsequent global cerebral ischemia-reperfusion. Brain homogenates of adult Wistar rats (n = 25) were analyzed for bcl-2 and bax mRNA expression using a new highly sensitive and quantitative polymerase chain reaction (PCR) technique that allows real-time fluorescence measurements of the PCR product (LightCycler; Roche Diagnostics, Mannheim, Germany). Animals for mRNA analysis received 3-NPA (20 mg/kg, intraperitoneal; "chemical preconditioning") or vehicle (normal saline), and were either observed for 24 plus 3 hours or were subjected to 15 minutes of global cerebral ischemia 24 hours after the pretreatment and observed for 3 hours of reperfusion. Immunohistochemistry was applied to serial brain sections of additional rats (n = 68) to determine amount and localization of the respective Bcl-2 and Bax protein expression in various brain areas. One set of animals was injected with 3-NPA and observed for 3, 12, 24, and 96 hours; a second set was exposed to 15 minutes global cerebral ischemia, 3, 12, and 24 hours reperfusion; and a third set was pretreated with 3-NPA or saline 24 hours before the ischemic brain insult and observed for 96 hours of reperfusion. The authors found single dose 3-NPA treatment to be associated with an elevated bcl-2:bax ratio (increased bcl-2 expression, decreased bax expression), both on the transcriptional (mRNA) and the translational (protein) level. The differential influence of 3-NPA was maintained during early recovery from global cerebral ischemia (3 hours), when 3-NPA pretreated animals showed higher bcl-2 and lower bax mRNA levels compared with rats with saline treatment. Respective changes in protein expression were localized predominately in neurons vulnerable to ischemic damage. Compared with baseline, Bcl-2 protein was significantly higher in surviving neurons at 96 hours after the insult, whereas Bax protein remained unchanged. However, at this late time of postischemic recovery (96 hours), the protein expression pattern of surviving neurons was not different between animals with and without 3-NPA pretreatment. To the authors' knowledge, the current study is the first report on the differential expression of pro- and antiapoptotic genes after a single, nonlethal dose of 3-NPA. The current results suggest alterations in the balance between pro- and antiapoptotic proteins as a potential explanation for the reported protection provided by chemical preconditioning using 3-NPA in rats.

The topics of international publications on paediatric anaesthesia from 1993 to 1998.

A comprehensive compilation of the current international literature on paediatric anaesthesia is still lacking. It was the aim of this study to identify all publications with a focus on paediatric anaesthesia, and to determine the spectrum of topics, as well as the publication type and language for the period between 1993 and 1998. All articles published in 12 major anaesthesia journals were evaluated and, additionally, a computerized, Internet-based Medline-search was performed using selected keywords. The analysis was limited to original articles, case reports, reviews and editorials. For the period between 1993 and 1998, a total of 2259 (377 per year) publications on paediatric anaesthesia were identified in 295 different journals, the majority of which were on the topic of 'providing anaesthesia' in children (n=1424, 63.0%). In contrast, publications on, for example, 'postanaesthesia care' (6. 3%), and 'organizational aspects of paediatric anaesthesia' (2.2%) were rare. Most articles were written in English (85.1%), and more than 50% reported original data (57.1%). Our results suggest that several topics may be of interest for future research and communication in the field of paediatric anaesthesia and new results should be published in English to reach a large international readership.

Neuronal death in newborn striatum after hypoxia-ischemia is necrosis and evolves with oxidative stress.

The mechanisms for neurodegeneration after hypoxia-ischemia (HI) in newborns are not understood. We tested the hypothesis that striatal neuron death is necrosis and evolves with oxidative stress and selective organelle damage. Piglets ( approximately 1 week old) were used in a model of hypoxia-asphyxia and survived for 3, 6, 12, or 24 h. Neuronal death was progressive over 3-24 h recovery, with approximately 80% of putaminal neurons dead at 24 h. Striatal DNA was digested randomly at 6-12 h. Ultrastructurally, dying neurons were necrotic. Damage to the Golgi apparatus and rough endoplasmic reticulum occurred at 3-12 h, while most mitochondria appeared intact until 12 h. Mitochondria showed early suppression of activity, then a transient burst of activity at 6 h, followed by mitochondrial failure (determined by cytochrome c oxidase assay). Cytochrome c was depleted at 6 h after HI and thereafter. Damage to lysosomes occurred within 3-6 h. By 3 h recovery, glutathione levels were reduced, and peroxynitrite-mediated oxidative damage to membrane proteins, determined by immunoblots for nitrotyrosine, occurred at 3-12 h. The Golgi apparatus and cytoskeleton were early targets for extensive tyrosine nitration. Striatal neurons also sustained hydroxyl radical damage to DNA and RNA within 6 h after HI. We conclude that early glutathione depletion and oxidative stress between 3 and 6 h reperfusion promote damage to membrane and cytoskeletal proteins, DNA and RNA, as well as damage to most organelles, thereby causing neuronal necrosis in the striatum of newborns after HI.

Control of brain temperature during experimental global ischemia in rats.

Temperature control during experimental ischemia continues to be of major interest. However, if exposure of brain tissue is necessary during the experiment, regional heat loss may occur even when the core temperature is maintained. Furthermore, valid non-invasive brain temperature monitoring is difficult in small rodents. This paper describes a method for both monitoring and maintenance of brain temperature during small animal preparations in a stereotaxic frame. The device used includes an ear-bar thermocouple probe and a small near-infrared radiator. The new equipment permitted to maintain peri-ischemic brain temperature at a desired level while carrying out non-invasive continuous recordings of cerebral blood flow (laser Doppler-flowmetry) and of electrical brain function (EEG). In contrast, without extracranial heat application, superficial and basal brain temperatures decreased during global cerebral ischemia by 4.1 +/- 0.1 and 4.6 +/- 0.4 degrees C (mean +/- SEM), respectively, returning to baseline values at 15-30 min of reperfusion while rectal (core) temperature remained stable at baseline values. The ear-bar thermocouple probe (tympanic membrane) reliably reflected basal brain temperature, and temperature in superficial brain areas correlated well with that in the temporal muscle. Our data show that the new system allows to exclude unwanted hypothermic neuroprotection, and does not interfere with optical and electrical measurement techniques.

Successful treatment of a patient with ARDS after pneumonectomy using high-frequency oscillatory ventilation.

High frequency oscillatory ventilation (HFOV) was used in a patient who developed the acute respiratory distress syndrome 5 days following a right pneumonectomy for bronchogenic carcinoma. When conventional pressure-controlled ventilation failed to maintain adequate oxygenation, HFOV dramatically improved oxygenation within the first few hours of therapy. Pulmonary function and gas exchange recovered during a 10-day period of HFOV. No negative side effects were observed. Early use of HFOV may be a beneficial ventilation strategy for adults with acute pulmonary failure, even in the postoperative period after lung resection.

Quantitative EEG during early recovery from hypoxic-ischemic injury in immature piglets: burst occurrence and duration.

This study examined the course of EEG recovery in an animal model of hypoxic-ischemic injury. The model used periods of hypoxia, room air and asphyxia to induce cardiac arrest. One-week-old piglets (n = 16) were exposed to a period of hypoxia, room air and complete asphyxia for 7 minutes. After cardiac arrest and resuscitation, two EEG features were evaluated as prognostic indicators of behavioral outcome as assessed by a neuroscore at 24 hours after insult. A prominent EEG feature was the number and duration of bursts evident during recovery. Episodes of bursting were detected through the thresholds on sustained periods of elevated power. After the animal was resuscitated, the EEG was monitored continuously for 4 hours. To assess outcome in the recovering animal, a behavioral testing scale was used to test the animal's neurological capabilities. Trends of EEG burst counts were measured through thresholds on sustained power changes. Bursts are energy transients in the EEG record. High degrees of bursting were characteristic of animals having good neurological condition whereas piglets having low burst counts had poor 24 hr neuroscores. At 100 min the average burst rate of the good neuroscore outcome group was more than 8 per min and was significantly different from the poor outcome group's level of 2.7 (p < or = 0.05). When these counts were weighted by their total duration, differences between groups increased (p < or = 0.02). This study showed that the QEEG measure of burst counts and duration together provided a strong prognostic indication of the 24 hour outcome after asphyxic injury in a neonatal animal model. The critical determinant of the bursting character was the time when bursting occurred. Bursting occurring early in recovery was a good gauge of outcome. We conclude that quantitative EEG analysis and interpretation can be an important tool for the outcome determination during recovery from cerebral injury states.

Effects of the AMPA receptor antagonist NBQX on outcome of newborn pigs after asphyxic cardiac arrest.

In neonates, asphyxia is a common cause of neuronal injury and often results in seizures. The authors evaluated whether blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors during asphyxia and early recovery with 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo-(F)-quinoxaline (NBQX) ameliorates neurologic deficit and histopathology in 1-week-old piglets. Anesthetized piglets were exposed to a sequence of 30 minutes of hypoxia, 5 minutes of room air ventilation, 7 minutes of airway occlusion, and cardiopulmonary resuscitation. Vehicle or NBQX was administered intravenously before asphyxia (30 mg/kg) and during the first 4 hours of recovery (15 mg/kg/h). Neuropathologic findings were evaluated at 96 hours of recovery by light microscopic and cytochrome oxidase histochemical study. Cardiac arrest occurred at 5 to 6 minutes of airway occlusion, and cardiopulmonary resuscitation restored spontaneous circulation independent of treatment modalities in about 2 to 3 minutes. Neurologic deficit over the 96-hour recovery period was not ameliorated by NBQX. Seizure activity began after 24 to 48 hours in 7 of 10 animals with vehicle and in 9 of 10 of animals with NBQX. In each group, four animals died in status epilepticus. Neuropathologic outcomes were not improved by NBQX. The density of remaining viable neurons was decreased in parietal cortex and putamen by NBQX treatment. Metabolic defects in cytochrome oxidase activity were worsened by NBQX treatment. Seizure activity during recovery was associated with reduced neuronal viability in neocortex and striatum in piglets from both groups that survived for 96 hours. This neonatal model of asphyxic cardiac arrest and resuscitation generates neurologic deficits, clinical seizure activity, and selective damage in regions of basal ganglia and sensorimotor cortex. In contrast to other studies in mature brain, AMPA receptor blockade with NBQX failed to protect against neurologic damage in the immature piglet and worsened postasphyxic histopathologic outcome in neocortex and putamen.

Effect of arrest time and cerebral perfusion pressure during cardiopulmonary resuscitation on cerebral blood flow, metabolism, adenosine triphosphate recovery, and pH in dogs.

OBJECTIVES: To test the hypothesis that greater cerebral perfusion pressure (CPP) is required to restore cerebral blood flow (CBF), oxygen metabolism, adenosine triphosphate (ATP), and intracellular pH (pHi) levels after variable periods of no-flow than to maintain them when cardiopulmonary resuscitation (CPR) is started immediately. DESIGN: Prospective, randomized, comparison of three arrest times and two perfusion pressures during CPR in 24 anesthetized dogs. SETTING: University cerebral resuscitation laboratory. INTERVENTIONS: We used radiolabeled microspheres to determine CBF and magnetic resonance spectroscopy to derive ATP and pHi levels before and during CPR. Ventricular fibrillation was induced, epinephrine administered, and thoracic vest CPR adjusted to provide a CPP of 25 or 35 mm Hg after arrest times of O, 6, or 12 mins. MEASUREMENTS AND MAIN RESULTS: When CPR was started immediately after arrest with a CPP of 25 mm Hg, CBF and ATP were 57 +/- 10% and 64 +/- 14% of prearrest (at 10 mins of CPR). In contrast, CBF and ATP were minimally restored with a CPP at 25 mm Hg after a 6-min arrest time (23 +/- 5%, 16 +/- 5%, respectively). With a CPP of 35 mm Hg, extending the no-flow arrest time from 6 to 12 mins reduced reflow from 71 +/- 11% to 37 +/- 7% of pre-arrest and reduced ATP recovery from 60 +/- 11% to 2 +/- 1% of pre-arrest. After 6- or 12-min arrest times, brainstem blood flow was restored more than supratentorial blood flow, but cerebral pHi was never restored. CONCLUSIONS: A CPP of 25 mm Hg maintains supratentorial blood flow and ATP at 60% to 70% when CPR starts immediately on arrest, but not after a 6-min delay. A higher CPP of 35 mm Hg is required to restore CBF and ATP when CPR is delayed for 6 mins. After a 12-min delay, even the CPP of 35 mm Hg is unable to restore CBF and ATP. Therefore, increasing the arrest time at these perfusion pressures increases the resistance to reflow sufficient to impair restoration of cerebral ATP.