0000000000003218
AUTHOR
Christian Werner
The Long-Term Effect of Sevoflurane on Neuronal Cell Damage and Expression of Apoptotic Factors After Cerebral Ischemia and Reperfusion in Rats
We investigated the long-term effects of sevoflurane on histopathologic injury and key proteins of apoptosis in a rat hemispheric ischemia/reperfusion model. Sixty-four male Sprague-Dawley rats were randomly assigned to Group 1 (fentanyl and N2O/O2; control) and Group 2 (2.0 vol% sevoflurane and O2/air). Ischemia (45 min) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension (mean arterial blood pressure 40 mm Hg). Animals were killed after 1, 3, 7, and 28 days. In hematoxylin and eosin-stained brain sections eosinophilic hippocampal neurons were counted. Activated caspase-3 and the apoptosis-regulating proteins Bax, Bcl-2, Mdm-2, and p53 were analyzed by i…
The effects of arterial carbon dioxide partial pressure and sevoflurane on capillary venous cerebral blood flow and oxygen saturation during craniotomy
Intraoperative routine monitoring of cerebral blood flow and oxygenation remains a technological challenge. Using the physiological principle of carbon dioxide reactivity of cerebral vasculature, we investigated a recently developed neuromonitoring device (oxygen-to-see, O2C device) for simultaneous measurements of regional cerebral blood flow (rvCBF), blood flow velocity (rvVelo), oxygen saturation (srvO2), and hemoglobin amount (rvHb) at the capillary venous level in patients subjected to craniotomy. METHODS: Twenty-six neurosurgical patients were randomly assigned to anesthesia with 1.4% or 2.0% sevoflurane end-tidal concentration. After craniotomy, a fiberoptic probe was applied on a ma…
Lay basic life support: the current situation in a medium-sized German town.
Objective Basic life support (BLS) by laypersons is essential for surviving sudden cardiac death in the community. The present study investigates BLS skill knowledge of German laypersons in a public community place and examines the effect of the interval between the last BLS course and present skills in cardiopulmonary resuscitation (CPR). Methods Participants were randomly recruited at a public place in a medium-sized German town. Volunteers were confronted with a fictitious cardiac arrest situation using a BLS training manikin and were asked to help. Using a standardised evaluation sheet, measures were documented. Participants9 demographic data were evaluated after completion of the scena…
Transmission of arterial oxygen partial pressure oscillations to the cerebral microcirculation in a porcine model of acute lung injury caused by cyclic recruitment and derecruitment.
Cyclic recruitment and derecruitment (R/D) play a key role in the pathomechanism of acute lung injury (ALI) leading to respiration-dependent oscillations of arterial partial pressure of oxygen (Pa(O(2))). These Pa(O(2)) oscillations could also be forwarded to the cerebral microcirculation.In 12 pigs, partial pressure of oxygen was measured in the thoracic aorta (Pa(O(2))) and subcortical cerebral tissue (Pbr(O(2))). Cerebral cortical haemoglobin oxygen saturation (Sbr(O(2))), cerebral blood flow (CBF), and peripheral haemoglobin saturation (Sp(O(2))) were assessed by spectroscopy and laser Doppler flowmetry. Measurements at different fractions of inspired oxygen (F(I(O(2)))) were performed …
Sevoflurane affects neurogenesis after forebrain ischemia in rats.
BACKGROUND: The effect of sevoflurane on the neuroregenerative potential after neuronal injury is unclear. We investigated the effect of low and high concentrations of sevoflurane on endogenous neurogenesis after cerebral ischemia. METHODS: Anesthetized and ventilated rats were randomized to four different treatment groups. Groups 1 and 2: 1.4% sevoflurane; Groups 3 and 4: 2.8% sevoflurane. In Groups 1 and 3, no cerebral ischemia was induced (sham-operated). In Groups 2 and 4, 10 min of forebrain ischemia was induced by bilateral carotid artery occlusion plus hemorrhagic hypotension. Physiological variables were maintained constant. Bromodeoxyuridine was given as a marker of neurogenesis. A…
Effect of autologous blood transfusion on cerebral cytokine expression.
BACKGROUND: Autologous blood transfusion (ABT), for example, by means of cell saver equipment, is used to reduce the need for allogenic blood transfusion in patients with high perioperative blood loss. This study investigated the effect of blood/extracorporal surface interaction during withdrawal and retransfusion of shed autologous blood on cerebral inflammation in rats. Rats subjected to hypotension with cerebral ischemia served as positive controls. METHODS: Eighty-eight male Sprague-Dawley rats were anesthetized with sevoflurane, instrumented, and randomly assigned to the following groups: sham-operation (SHAM), autologous blood withdrawal/transfusion only (ABT), or bilateral carotid ar…
Xenon treatment improves short-term and long-term outcomes in a rodent model of traumatic brain injury
Postoperative nausea and vomiting in patients after craniotomy: incidence and risk factors
Object The purpose of this study was to assess the incidence and risk factors of postoperative nausea and vomiting (PONV) after craniotomy because most available data about PONV in neurosurgical patients are retrospective in nature or derive from small prospective studies. Methods Postoperative nausea and vomiting was prospectively assessed within 24 hours after surgery in 229 patients requiring supratentorial or infratentorial craniotomy. To rule out the relevance of the neurosurgical procedure itself to the development of PONV, the observed incidence of vomiting was compared with the rate of vomiting predicted with a surgery-independent risk score (Apfel postoperative vomiting score). Re…
High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats
Abstract Purpose : Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. Methods : Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mmHg for…
Pathogenic lipid‐binding antiphospholipid antibodies are associated with severity of COVID‐19
Abstract Background Coronavirus disease 19 (COVID‐19)–associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome—microvascular thrombosis, stroke, and venous and pulmonary clots—are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID‐19 patients, but their association with the clinical course of COVID‐19 remains unproven. Objectives To analyze the presence and relevance of lipid‐binding aPL in hospitalized COVID‐19 patients. Methods Two cohorts of 53 and 121 patients from a single center hospitalized for PCR‐proven severe acute respiratory syndro…
Evaluation of the novel, single-use, flexible aScope® for tracheal intubation in the simulated difficult airway and first clinical experiences
Flexible fibreoptic intubation is widely accepted as an important modality for the management of patients with difficult airways. We compared the aScope, a novel, single-use, flexible video-endoscope designed to aid tracheal intubation, with a standard flexible intubating fibrescope, by examining the performance of 21 anaesthetists during an easy and difficult intubation simulation in a manikin. Intubation success, time for intubation, and rating of the devices (using a scale from 1, excellent to 6, fail) were documented. Intubation times were similar for both flexible 'scopes in the scenarios (p = 0.59). Successful intubation rates were higher for the standard intubating fibrescope (17/21,…
Effects of sevoflurane on cognitive deficit, motor function, and histopathology after cerebral ischemia in rats.
Background: The volatile anesthetic sevoflurane exhibits neuroprotective properties when assessed for motor function and histopathology after cerebral ischemia in rats. Damage of hippocampal neurons after ischemia relates to a number of cognitive deficits that are not revealed by testing animals for motor function. Therefore, the present study evaluates cognitive and behavioral function as well as hippocampal damage in rats subjected to cerebral ischemia under sevoflurane compared with fentanyl/nitrous oxide (N 2 O)/O 2 anesthesia. Methods: Thirty-four rats were trained for 10 days using a hole-board test to detect changes in cognitive and behavioral function. Rats were randomly assigned to…
Sevoflurane Impairs Cerebral Blood Flow Autoregulation in Rats: Reversal by Nonselective Nitric Oxide Synthase Inhibition
UNLABELLED In this study, we investigated the effects of 1.0 and 2.0 minimum alveolar anesthetic concentration (MAC) sevoflurane on cerebral blood flow (CBF) autoregulation before and after nonselective inhibition of nitric oxide (NO) synthase in rats. Rats were randomly assigned as follows: Group 1 (n = 8): 1.0 MAC sevoflurane; Groups 2 and 3 (n = 8 per group): 2.0 MAC sevoflurane. Assessment of autoregulation within a mean arterial blood pressure range of 140-60 mm Hg was performed by graded hemorrhage before and after administration of l-arginine methyl ester (l-NAME, 30 mg/kg IV, Groups 1 and 2) or during hypocapnia (Group 3). In 10 additional animals, brain tissue NO(2)(-) concentratio…
Comparison of different quantification methods to determine hippocampal damage after cerebral ischemia
Abstract Background Experimental stroke studies use multiple techniques to evaluate histopathological damage. Unfortunately, sensitivity and reproducibility of these techniques are poorly characterized despite pivotal influence on results. Method The present study compared several quantification methods to differentiate between two severities of global cerebral ischemia and reperfusion. Male Sprague-Dawley rats were randomized to moderate (10 min) or severe (14 min) ischemia by bilateral carotid occlusion (BCAO) with hemorrhagic hypotension. Neuronal cell count was determined in hippocampus at bregma −3.14 mm and −3.8 mm on day 3 and 28 post insult by counting neurons in the whole CA1 or in…
Postshock rhythm after first defibrillation of out-of-hospital cardiac arrest patients in ventricular fibrillation: An early outcome predictor
Prospective assessment of postoperative pain after craniotomy.
Pain after craniotomy may be underdiagnosed, despite the fact that it can increase postoperative complications for example arterial hypertension and postoperative hemorrhage. This study investigates the incidence and intensity of pain after craniotomy and characterizes the influencing parameters. During a 1-year period 256 patients undergoing elective craniotomy were prospectively included in the study. Intensity of pain was evaluated 1, 4, and 24 hours after extubation using a verbal numerical rating scale (NRS) ranging from 0 (no pain) to 10 (maximal pain). Routine perioperative pain management was not influenced by the investigators. Parameters including patient-related factors, drug adm…
Influence of a Brief Episode of Anesthesia during the Induction of Experimental Brain Trauma on Secondary Brain Damage and Inflammation
It is unclear whether a single, brief, 15-minute episode of background anesthesia already modulates delayed secondary processes after experimental brain injury. Therefore, this study was designed to characterize three anesthesia protocols for their effect on molecular and histological study endpoints. Mice were randomly separated into groups that received sevoflurane (sevo), isoflurane (iso) or an intraperitoneal anesthetic combination (midazolam, fentanyl and medetomidine; comb) prior to traumatic brain injury (controlled cortical impact, CCI; 8 m/s, 1 mm impact depth, 3 mm diameter). Twenty-four hours after insult, histological brain damage, neurological function (via neurological severit…
Dose-dependent effect of S(+) ketamine on post-ischemic endogenous neurogenesis in rats.
Background: Ketamine is a non-competitive antagonist at N-methyl-d-aspartate (NMDA) receptors and reduces neuronal injury after cerebral ischemia by blocking the excitotoxic effects of glutamate. However, cerebral regeneration by means of endogenous neurogenesis may be impaired with blockade of NMDA receptors. The effects of S(+) ketamine on post-ischemic neurogenesis are unknown and investigated in this study. Methods: Thirty-two male Sprague–Dawley rats were randomly assigned to the following treatment groups with intravenous S(+) ketamine anesthesia: S(+) ketamine 0.75 mg/kg/min with or without cerebral ischemia and S(+) ketamine 1.0 mg/kg/min with or without cerebral ischemia. Eight non…
Posttraumatic Propofol Neurotoxicity Is Mediated via the Pro–Brain-Derived Neurotrophic Factor-p75 Neurotrophin Receptor Pathway in Adult Mice*
Objectives:The gamma-aminobutyric acid modulator propofol induces neuronal cell death in healthy immature brains by unbalancing neurotrophin homeostasis via p75 neurotrophin receptor signaling. In adulthood, p75 neurotrophin receptor becomes down-regulated and propofol loses its neurotoxic effect. H
Measurement of Cortical Microcirculation During Intracranial Aneurysm Surgery by Combined Laser-Doppler Flowmetry and Photospectrometry
Accidental vessel occlusion is one major risk of intracranial aneurysm surgery potentially causing cerebral ischemia. The intraoperative assessment of cerebral ischemia remains a technological challenge.As a novel approach, cortical tissue integrity was monitored using simultaneous measurements of regional capillary-venous cerebral blood flow (rvCBF), oxygen saturation (Srvo2), and hemoglobin amount (rvHb) during aneurysm surgery.Fifteen patients scheduled for aneurysm surgery of the anterior and posterior circulation were included. A fiber optic probe was placed on the cortex associated with the distal branch of the aneurysmatic vessel. Blinded measurements by combined laser-Doppler flowme…
Xenon Improves Neurologic Outcome and Reduces Secondary Injury Following Trauma in an In Vivo Model of Traumatic Brain Injury*
Objectives: To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury and to determine whether application of xenon has a clinically relevant therapeutic time window. Design: Controlled animal study. Setting: University research laboratory. Subjects: Male C57BL/6N mice (n = 196). Interventions: Seventy-five percent xenon, 50% xenon, or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact. Measurements and Main Results: Outcome following trauma was measured using 1) functional neurologic outcome score, 2) histological measurement of contusion volume, and 3) analysis of locomotor functio…
Pathophysiology of traumatic brain injury.
The knowledge of the pathophysiology after traumatic head injury is necessary for adequate and patient-oriented treatment. As the primary insult, which represents the direct mechanical damage, cannot be therapeutically influenced, target of the treatment is the limitation of the secondary damage (delayed non-mechanical damage). It is influenced by changes in cerebral blood flow (hypo- and hyperperfusion), impairment of cerebrovascular autoregulation, cerebral metabolic dysfunction and inadequate cerebral oxygenation. Furthermore, excitotoxic cell damage and inflammation may lead to apoptotic and necrotic cell death. Understanding the multidimensional cascade of secondary brain injury offers…
Assessment of postischemic neurogenesis in rats with cerebral ischemia and propofol anesthesia.
Background Postischemic endogenous neurogenesis can be dose-dependently modulated by volatile anesthetics. The intravenous anesthetic propofol is used during operations with a risk of cerebral ischemia, such as neurosurgery, cardiac surgery, and vascular surgery. The effects of propofol on neurogenesis are unknown and, therefore, the object of this study. Methods Eighty male Sprague-Dawley rats were randomly assigned to treatment groups with propofol administration for 3 h: 36 mg x kg(-1) x h(-1) propofol with or without cerebral ischemia and 72 mg x kg(-1) x h(-1) propofol with or without cerebral ischemia. In addition, 7 rats with propofol administration for 6 h and 14 treatment-naive ra…
Postoperatives kognitives Defizit bei alten Patienten
Postoperative congnitive dysfunction occurs in geriatric patients after major operations and influences morbidity and mortality of these patients. Clinical observations and neuropsychological tests can be used to diagnose cognitive disorders after an operation. Until today no specific medical treatment is known for the therapy of cognitive dysfunctions after an operation and, therefore, in high risk patients perioperative preventive measures is the only way to decrease the incidence and extend of this disease.
Nasotracheal intubation: look before you leap
Nasotracheal intubation is frequently used for airway management during maxillofacial surgery. Complications such as haemorrhage occur more frequently with this route of intubation than with the orotracheal route. This case report describes a male patient aged 51 yr who developed severe epistaxis after the tube had passed the nares. As an additional complication laryngoscopy and endotracheal intubation failed because of difficult airway (Cormack-Lehane grade 4). Attempts using an intubating laryngeal mask airway and a Bonfils intubating fibrescope did not succeed. The airway was finally managed by cricothyroidotomy. A modified sequence of nasotracheal intubation is proposed to avoid similar…
Changes in cerebral oxygen saturation following prone positioning for orthopaedic surgery under general anaesthesia: a prospective observational study.
Prone positioning is often necessary in orthopaedic surgery. The prone position, however, may result in impaired cerebral venous drainage with a subsequent reduction in cerebral perfusion. As a consequence, cerebral hypoxia may occur with the potential for neurological impairment.We assessed the changes in cerebral oxygen saturation with near-infrared spectroscopy using two different monitors after positioning the patient from supine to prone.Prospective observational study.Primary Care University Hospital, from May 2010 to February 2011.Forty patients undergoing general anaesthetic procedures, of which 35 completed the investigation. Similar measurements were done in 35 volunteers, who wer…
Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium
Introduction Sepsis-associated delirium (SAD) increases morbidity in septic patients and, therefore, factors contributing to SAD should be further characterized. One possible mechanism might be the impairment of cerebrovascular autoregulation (AR) by sepsis, leading to cerebral hypo- or hyperperfusion in these haemodynamically unstable patients. Therefore, the present study investigates the relationship between the incidence of SAD and the status of AR during sepsis. Methods Cerebral blood flow velocity was measured using transcranial Doppler sonography and was correlated with the invasive arterial blood pressure curve to calculate the index of AR Mx (Mx>0.3 indicates impaired AR). Mx was m…
Pioglitazone Reduces Secondary Brain Damage after Experimental Brain Trauma by PPAR-γ-Independent Mechanisms
Inflammatory and ischemic processes contribute to the development of secondary brain damage after mechanical brain injury. Recent data suggest that thiazolidinediones (TZDs), a class of drugs approved for the treatment of non-insulin-dependent diabetes mellitus, effectively reduces inflammation and brain lesion by stimulation of the peroxisome proliferator-activated receptor-γ (PPAR-γ). The present study investigates the influence of the TZD pioglitazone and rosiglitazone on inflammation and secondary brain damage after experimental traumatic brain injury (TBI). A controlled cortical impact (CCI) injury was induced in male C57BL/6 mice to investigate following endpoints: (1) mRNA expression…
Influence of Propofol on Neuronal Damage and Apoptotic Factors after Incomplete Cerebral Ischemia and Reperfusion in Rats
Background Propofol reduces neuronal damage from cerebral ischemia when investigated for less than 8 postischemic days. This study investigates the long-term effects of propofol on neuronal damage and apoptosis-related proteins after cerebral ischemia and reperfusion. Methods Male Sprague-Dawley rats were randomly assigned as follows: group 1 (n = 32, control): fentanyl and nitrous oxide-oxygen; group 2 (n = 32, propofol): propofol and oxygen-air. Ischemia (45 min) was induced by carotid artery occlusion and hemorrhagic hypotension. Pericranial temperature and arterial blood gases were maintained constant. After 1, 3, 7, and 28 postischemic days, brains were removed, frozen, and sliced. Hi…
Cross-clamping a porcelain aorta: an alternative technique for high-risk patients
Background Aortic cross-clamping in patients with porcelain aorta is associated with high mortality and morbidity rates. The aim is to establish a new approach to improve the outcome in this high-risk population. Methods Between September 2007 and November 2012, 42 patients with an aortic (N.=33; 81.3±6.4 years) or mitral valve disease (N.=9; 80.3±5.7) combined with a porcelain aorta underwent aortic (AVR) or mitral valve replacement (MVR). After arterial cannulation via distal aortic arch or femoral artery, longitudinal aortotomy under total cardiopulmonary bypass (CPB) was performed. The aorta was slowly clamped, thus mobilized atherosclerotic material could leave the aorta through the op…
Serial Measurement of Static and Dynamic Cerebrovascular Autoregulation After Brain Injury
In patients with neuronal injury, the knowledge of the status of cerebrovascular autoregulation can help to optimize the management of the cerebral perfusion pressure. This study characterizes dynamic and static cerebrovascular autoregulation during the first 7 days after severe traumatic brain injury or intracranial hemorrhage.After approval from the IRB, 16 patients were studied. Cerebral blood flow velocity (CBFV) was measured daily for the assessment of dynamic (10 patients) and static (16 patients) cerebrovascular autoregulation in both the middle cerebral arteries using the transcranial Doppler sonography. Dynamic cerebrovascular autoregulation (dAR) was measured using the cuff-deflat…
Intraoperative monitoring of cerebral microcirculation and oxygenation--a feasibility study using a novel photo-spectrometric laser-Doppler flowmetry.
The present study assesses the utility of a novel invasive device (O2C-, oxygen-to-see-device) for intraoperative measurement of the cerebral microcirculation. CO2 vasoreactivity during 2 different propofol concentrations was used to investigate changes of capillary venous cerebral blood flow (rvCBF), oxygen saturation (srvO2), and hemoglobin concentration (rvHb) during craniotomy.Thirty-four patients were randomly assigned to a low propofol (4 mg/kg/h) versus a high propofol (6 mg/kg/h) group. A fiberoptic probe was applied on the cortex next to the surgical site. Measurements were performed during lower (35 mm Hg) and higher (45 mm Hg) levels of partial pressure of carbon dioxide (paCO2).…
Human cerebral microcirculation and oxygen saturation during propofol-induced reduction of bispectral index †
† This study investigates the effects of propofol-induced changes in bispectral index (BIS) on cerebral microcirculation and oxygenation during craniotomies. † In 2 mm cerebral depth, an increase in propofol dosage resulted in increased oxygen saturation (srvO2 )w ithout reduction of capillary venous blood flow (rvCBF). † Difference in oxygen content (avDO2) and approximated cerebralmetabolicrateofoxygen (aCMRO2) decreased with an increase in propofol dosage in 2 mm cerebral depth. † Alterations in BIS showed no effect on rvCBF, srvO2 ,a nd haemoglobin amount (rvHb) or on avDO2 or aCMRO2 in 8 mm cerebral depth. † These findings suggest that the CBF/CMRO2 ratio is altered by propofol in a re…
Two-rescuer CPR results in hyperventilation in the ventilating rescuer.
The "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care--International Consensus on Science" recommend a tidal ventilation volume of 10 ml/kg body-weight without the use of supplemental oxygen during two-rescuer adult cardiopulmonary resuscitation (CPR). This relates to a ventilation volume of about 6.4 l/min. Additionally, the first aid provider ventilating the victim will breathe for him/herself during the external chest compression period adding another 3.2 l/min of ventilation. Finally, a deep breath is recommended before each ventilation to increase the end-expiratory oxygen concentration of the air exhaled. To investigate the effects of these recommend…
Transpulmonary cardiac output measurement in a rat model of cardiac arrest and CPR: Impact of vascular access
Objective: The present study investigated the impact of the vascular access site for cardiac output (CO) measurement by thermodilution on survival and neurohistopathological injury in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Secondary the influence of the vascular access site on cardiac output measurements was examined. Methods: Rats underwent asphyxial CA and CPR. Thermocouple probes were either placed via the femoral artery into the bifurcation of abdominal aorta/iliac artery (Femoral) or via the carotid artery into the aortic arch (Carotid). CPR was initiated after 9 min CA. Local cerebral blood flow (lCBF) and CO were assessed for 120 min after restora…
Isoflurane is associated with a similar incidence of emergence agitation/delirium as sevoflurane in young children ? a randomized controlled study
Summary Background: Children may be agitated or even delirious especially when recovering from general anesthesia using volatile anesthetics. Many trials have focused on the newer agents sevoflurane and desflurane but for the widely used isoflurane little is known about its potential to generate agitation. We investigated the emergence characteristics of small children after sevoflurane or isoflurane with caudal anesthesia for postoperative pain control. Methods: After institutional approval and parental consent, anesthesia was randomly performed with sevoflurane (n = 30) or isoflurane (n = 29) in children at the age of 3.8 ± 1.8 years during surgical interventions on the lower part of th…
Proneurotrophin Binding to P75 Neurotrophin Receptor (P75ntr) Is Essential for Brain Lesion Formation and Functional Impairment after Experimental Traumatic Brain Injury
Traumatic brain injury (TBI) initiates an excessive mediator release of e.g. neurotrophins, which promote neuronal survival, differentiation, and modulate synaptic plasticity. Paradoxically, mature forms of neurotrophins promote neuronal survival, whereas unprocessed forms of neurotrophins induce cell death through p75 neurotrophin receptor (p75NTR) signaling. p75NTR is widely expressed during synaptogenesis and is subsequently downregulated in adulthood. Repair mechanisms after acute cerebral insults can reactivate its expression. Therefore, the influence of p75NTR on secondary brain damage was addressed. mRNA levels of p75NTR and its ligands were quantified in brain tissue up to 7 days af…
Evidence for a negative inotropic effect of obesity in human myocardium?
Objective: The present study was performed as an attempt to analyze the relationship between body weight and human myocardial performance. As overweight is frequently associated with hypertension, stenosis of epimyocardial coronary arteries and other factors that influence myocardial performance, the experimental model of isolated human atrial myocardium was selected. Atrial contractile performance does neither depend on the extent of stenosis of epicardial coronary arteries nor on the degree of hypertension and its secondary pathology. Methods:Rightatrialmusclepreparations(0.5 6 mm)of183patientsundergoingcoronaryarterybypasssurgerywereelectricallystimulatedat optimal length. Active tension…
Postoperative analgesic efficacy of peripheral levobupivacaine and ropivacaine: a prospective, randomized double-blind trial in patients after total knee arthroplasty.
BACKGROUND: Several previous trials have characterized the intra- and postoperative effects of the recently introduced local anesthetics, levobupivacaine and ropivacaine, for a variety of continuous peripheral nerve blocks. METHODS: We compared the analgesic efficacy of levobupivacaine 0.125% versus ropivacaine 0.2% via patient-controlled femoral nerve analgesia after total knee arthroplasty. In a double-blind, randomized, prospective design, 60 patients received femoral infusion with either substance. We analyzed postoperative local anesthetic consumption, pain scores, motor block, and opioid requirements over 72 h. RESULTS: Pain scores, motor block incidence, and opioid requirements were …
Influence of Beach Chair Position on Cerebral Oxygen Saturation
Although beach chair position (BCP) is frequently used for shoulder surgery, a potentially detrimental influence on cerebral oxygenation is discussed. Therefore, the present study investigated changes in regional cerebral oxygen saturation (rSO2/StO2) during BCP comparing 2 different devices for near-infrared spectroscopy measurement.Data were collected in 35 patients undergoing shoulder surgery in BCP and compared with a control group of 35 awake volunteers. The rSO2/StO2 was assessed using INVOS and FORE-SIGHT monitors. Mean arterial blood pressure (MAP), peripheral oxygen saturation (SpO2), PeCO2, FiO2, end-tidal sevoflurane concentration, and rSO2/StO2 were measured before positioning, …
PaO2oscillations caused by cyclic alveolar recruitment can be monitored in pig buccal mucosa microcirculation
BACKGROUND Cyclic alveolar recruitment and derecruitment play a role in the pathomechanism of acute lung injury and may lead to arterial partial pressure of oxygen (PaO(2) ) oscillations within the respiratory cycle. It remains unknown, however, if these PaO(2) oscillations are transmitted to the microcirculation. The present study investigates if PaO(2) oscillations can be detected in the pig buccal mucosa microcirculation. METHODS Respiratory failure was induced by surfactant depletion in seven pigs. PaO(2) oscillations caused by cyclic recruitment and derecruitment were measured in the thoracic aorta by fast fluorescence quenching of oxygen technology. Haemoglobin oxygen saturation, haem…
A review of the importance of mineral nitrogen cycling in the plant-soil-microbe system of permafrost-affected soils : changing the paradigm
The paradigm that permafrost-affected soils show restricted mineral nitrogen (N) cycling in favor of organic N compounds is based on the observation that net N mineralization rates in these cold climates are negligible. However, we find here that this perception is wrong. By synthesizing published data on N cycling in the plant-soil-microbe system of permafrost ecosystems we show that gross ammonification and nitrification rates in active layers were of similar magnitude and showed a similar dependence on soil organic carbon (C) and total N concentrations as observed in temperate and tropical systems. Moreover, high protein depolymerization rates and only marginal effects of C:N stoichiomet…
Propofol Impairs Neurogenesis and Neurologic Recovery and Increases Mortality Rate in Adult Rats After Traumatic Brain Injury*
Objective: Limited data are available on the influence of sedation for critical care therapy with the widely used anesthetic propofol on recovery from acute traumatic brain injury. To establish the influence of propofol on endogenous neurogenesis and functional recovery after traumatic brain injury, rats were sedated with propofol either during or 2 hours after experimental traumatic brain injury. Design: Randomized controlled animal study. Setting: University research laboratory. Subjects: One hundred sixteen male Sprague Dawley rats. Interventions: Mechanical brain lesion by controlled cortical impact. Measurements and Main Results: This study investigated the dose-dependent influence of …
Effects of a single-dose hypertonic saline hydroxyethyl starch on cerebral blood flow, long-term outcome, neurogenesis, and neuronal survival after cardiac arrest and cardiopulmonary resuscitation in rats*
The beneficial effects of hypertonic saline on neuronal survival and on cerebral blood flow have been shown in several animal models of global and focal brain ischemia. Because of the potential benefits of hypertonic solutions, it is hypothesized that hydroxyethyl starch enhances cerebral blood flow and improves long-term outcome after cardiac arrest and cardiopulmonary resuscitation in an animal model.Laboratory animal study.University animal research laboratory.Fifty-nine male Sprague-Dawley rats.Rats were randomized to receive either 7.2% saline/6% hypertonic saline hydroxyethyl starch (4 mL/kg) or vehicle (NaCl 0.9 %) after 9 mins of asphyxic cardiac arrest and cardiopulmonary resuscita…
Mild Hypothermia Has No Long-Term Impact on Postischemic Neurogenesis in Rats
Postischemic improvement of functional outcome by therapeutic hypothermia may be related to cerebral regeneration by postischemic neurogenesis. We investigated whether mild peri-ischemic hypothermia leads to a long-term increase in postischemic neurogenesis.Seventy male sevoflurane-anesthetized Sprague Dawley rats were randomly assigned to the following treatment groups: normothermic ischemia, intraischemic hypothermia, and postischemic hypothermia with corresponding sham-operated controls. Fifteen naïve rats were investigated as reference for natural neurogenesis. Forebrain ischemia was induced by bilateral common carotid artery occlusion and hemorrhagic hypotension. In normothermic groups…
Inhibition of myosin light chain kinase reduces brain edema formation after traumatic brain injury.
The role of the endothelial contractile apparatus in the process of brain edema formation after brain trauma is not characterized. Phosphorylation of myosin light chains by myosin light chain kinases (MLCK) activates endothelial contractile elements and results in a rearrangement of the cytoskeleton. This may enhance post-traumatic blood-brain barrier dysfunction. In order to investigate the role of the MLCK on brain edema formation and blood-brain barrier permeability after brain injury, mice were anesthetized and subjected to a controlled cortical impact (CCI). MLCK expression is significantly up-regulated after CCI with a maximum 12 h post-injury. Specific inhibition of MLCK by ML-7 resu…
Delayed inhibition of angiotensin II receptor type 1 reduces secondary brain damage and improves functional recovery after experimental brain trauma*
OBJECTIVE:: To investigate the regulation of the cerebral renin-angiotensin system and the effect of angiotensin II receptor type 1 inhibition on secondary brain damage, cerebral inflammation, and neurologic outcome after head trauma. DESIGN:: The expression of renin-angiotensin system components was determined at 15 mins, 3 hrs, 6 hrs, 12 hrs, and 24 hrs after controlled cortical impact in mice. Angiotensin II receptor type 1 was inhibited using candesartan (0.1, 0.5, 1 mg/kg) after trauma to determine its effect on secondary brain damage, brain edema formation, and inflammation. The window of opportunity was tested by delaying angiotensin II receptor type 1 inhibition for 30 mins, 1 hr, 2…
RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up
Background Remote ischemic preconditioning ( RIPC ) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham‐ RIPC . Methods and Results In this follow‐up paper, we present 1‐year follow‐up of the composite primary end point and its individual components (all‐cause mortality, myocardial infarction, stroke and acute renal failure), in a sub‐group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidenc…
Comparison of two different techniques of fibreoptic intubation
BACKGROUND AND OBJECTIVE The application of analgesics and sedatives during fibreoptic intubation (FOI) may result in a transient decrease in arterial oxygen saturation.This study evaluates two different techniques of FOI and respective effects on procedural duration, arterial oxygen saturation, and coughing by the patient. METHODS Thirty-four patients received a standardized conscious sedation with fentanyl (1.5 microg kg(-1)) and midazolam (12.5 microg kg(-1)).All patients were randomly allocated to one of the following techniques: the 'vaporization' (VAP) technique included four applications of 2 ml lidocaine 2% administered through the working channel of the fibrescope supplying an oxyg…
Time course of cerebrovascular autoregulation during extreme Trendelenburg position for robotic-assisted prostatic surgery
Trendelenburg positioning in combination with pneumoperitoneum during robotic-assisted prostatic surgery possibly impairs cerebrovascular autoregulation. If cerebrovascular autoregulation is disturbed, arterial hypertension might induce cerebral hyperaemia and brain oedema, while low arterial blood pressure can induce cerebral ischaemia. The time course of cerebrovascular autoregulation was investigated during use of the Trendelenburg position and a pneumoperitoneum for robotic-assisted prostatic surgery using transcranial Doppler ultrasound. Cerebral blood flow velocity was correlated with arterial blood pressure and the autoregulation index (Mx) was calculated. In 23 male patients, Mx was…
Selection of endogenous control genes for normalization of gene expression analysis after experimental brain trauma in mice.
Quantitative measurements of gene expression require correction for tissue sample size, RNA quantity, and reverse transcription efficiency. This can be achieved by normalization with control genes. The study was designed to identify candidates not altered after brain trauma. Male C57Bl/6 mice were anesthetized with isoflurane, and a pneumatic brain trauma was induced by controlled cortical impact (CCI) on the right parietal cortex. Brains were removed at 15 min, and 3, 6, 12 and 24 h after CCI and from naive animals (n = 6 each). Absolute copies of six control genes (beta-2-microglobin [B2M], cyclophilin A, beta-actin, hypoxanthine ribosyltransferase [HPRT], porphobilinogen deaminase [PBGD]…
Inhalational or intravenous anesthetics for craniotomies? Pro inhalational.
In neurosurgery, anesthesiologists and surgeons focus on the same target - the brain. The nature of anesthetics is to interact with brain physiology, leading to favorable and adverse effects. Research in neuroanesthesia over the last three decades has been dedicated to identifying the optimal anesthetic agent to maintain coupling between cerebral blood flow and metabolism, keep cerebrovascular autoregulation intact, and not increase cerebral blood volume and intracranial pressure.Sevoflurane is less vasoactive than halothane, enflurane, isoflurane, or desflurane. The context sensitive half-life is short and similar to that of desflurane, which translates into fast on and offset. Compared wi…
Evaluation of the McGrath® Series 5 videolaryngoscope after failed direct laryngoscopy*
Summary Unanticipated difficulties during tracheal intubation and failure to intubate are among the leading causes of anaesthesia-related morbidity and mortality. Using the technique of video laryngoscopy, the alignment of the oral and pharyngeal axes to facilitate tracheal intubation is unnecessary. In this study we evaluated the McGrath® Series 5 videolaryngoscope for tracheal intubation in 61 patients who exhibited Cormack and Lehane grade 3 or 4 laryngoscopies with a Macintosh laryngoscope. Using the McGrath resulted in an improved glottic view, compared to Macintosh laryngoscope. Laryngoscopy was improved by one grade in 10%, by two grades in 80% and by three grades in 10% of cases (p …
Anesthesia for Euthanasia Influences mRNA Expression in Healthy Mice and after Traumatic Brain Injury
Tissue sampling for gene expression analysis is usually performed under general anesthesia. Anesthetics are known to modulate hemodynamics, receptor-mediated signaling cascades, and outcome parameters. The present study determined the influence of anesthetic paradigms typically used for euthanization and tissue sampling on cerebral mRNA expression in mice. Naïve mice and animals with acute traumatic brain injury induced by controlled cortical impact (CCI) were randomized to the following euthanasia protocols (n=10-11/group): no anesthesia (NA), 1 min of 4 vol% isoflurane in room air (ISO), 3 min of a combination of 5 mg/kg midazolam, 0.05 mg/kg fentanyl, and 0.5 mg/kg medetomidine intraperi…
Influence of PEEP on cerebral blood flow and cerebrovascular autoregulation in patients with acute respiratory distress syndrome.
High levels of positive end-expiratory pressure (PEEP), as part of the treatment in patients with acute respiratory distress syndrome (ARDS), may prevent alveolar collapse and maintain oxygenation. PEEP potentially reduces cerebral venous return, increases intracranial blood volume, and may, therefore, affect cerebral blood flow (CBF) and cerebrovascular autoregulation (AR). This study investigates the effect of PEEP on CBF and AR in patients with respiratory failure.CBF velocity was measured using transcranial doppler and correlated with the invasive arterial blood pressure curve to calculate the index of AR Mx (Mx0.3 indicates impaired AR). Mx was measured at lower PEEP levels and after i…
Robotic assisted prostatic surgery in the Trendelenburg position does not impair cerebral oxygenation measured using two different monitors: A clinical observational study.
Robotic assisted prostatic surgery is frequently used because of its reduced side-effects compared with conventional surgery. During surgery, an extreme Trendelenburg position and CO2 pneumoperitoneum are necessary, which may lead to cerebral oedema, can potentially reduce brain perfusion and therefore could impair cerebral oxygenation. Cerebral oxygen saturation can be measured non-invasively using near-infrared spectroscopy (NIRS).The hypothesis of the present study was that steep Trendelenburg positioning during robotic assisted prostatic surgery impairs cerebral oxygen saturation measured using two different NIRS monitors.Clinical observational study.Primary care university hospital, st…
Extracorporeal circulation and cardiac arrest in an awake patient: a safe approach for single lung pulmonary artery stenting?
We describe the anesthetic concept and approach in a single lung patient scheduled for pulmonary artery stenting due to recurrence of a pulmonary artery sarcoma after left pneumectomy.
2-Methoxyestradiol confers neuroprotection and inhibits a maladaptive HIF-1α response after traumatic brain injury in mice
HIF-1α is pivotal for cellular homeostasis in response to cerebral ischemia. Pharmacological inhibition of HIF-1α may reduce secondary brain damage by targeting post-translational mechanisms associated with its proteasomal degradation and nuclear translocation. This study examined the neuroprotective effects of 2-methoxyestradiol (2ME2), the involved HIF-1α-dependent response, and alternative splicing in exon 14 of HIF-1α (HIF-1α∆Ex14) after traumatic brain injury (TBI) in mice. Intraperitoneal 2ME2 administration 30 min after TBI caused a dose-dependent reduction in secondary brain damage after 24 h. 2ME2 was physiologically tolerated, showed no effects on immune cell brain migration, and …
Infraglottic airway devices and techniques.
Airway management involves far more than just proficiency with tracheal intubation techniques. There are several infraglottic techniques available and the method chosen will depend on the accessibility of equipment, the level of training and expertise, and the patient's specific injury or disease. Endotracheal intubation is most commonly performed by direct laryngoscopy. Several modifications of laryngoscope blades and a variety of adjuncts such as bougies may help to accomplish even a difficult airway. Rigid intubation fibrescopes do improve the view of the larynx, especially in patients with difficult anatomy. They also permit tracheal intubation with less head and cervical spine movement…
Performance of the C-MAC video laryngoscope in patients after a limited glottic view using Macintosh laryngoscopy
We applied the C-MAC videolaryngoscope in 52 consecutive patients who were found to have an unexpected Cormack and Lehane grade-3 (n = 49) and grade-4 (n = 3) laryngeal view with the Macintosh laryngoscope. The glottic view improved in 49 (94%) patients using the C-MAC. Tracheal intubation was successful in 49 of 52 patients (94%). In one patient, tracheal intubation failed using the C-MAC despite the presence of a Cormack and Lehane grade-2. These results suggest that the C-MAC videolaryngoscope has a role as a rescue device in cases of an initially difficult laryngeal view.
High-intensity transient signals during laparoscopic surgery in children.
Background Laparoscopic interventions in children gain increasing popularity. Pneumoperitoneum as applied during laparoscopic surgery can induce gas emboli formation, but it is unclear whether this is associated with cerebral embolic events. To investigate the hypothesis that pneumoperitoneum causes cerebral emboli in children, the number and intensity of high-intensity transient signals (HITS) detected using transcranial Doppler ultrasonography were assessed before and after induction of pneumoperitoneum. Methods Twenty children were monitored during laparoscopic surgery. General anaesthesia was performed using sevoflurane and sufentanil or alfentanil. Pressure-controlled ventilation was a…
Sevoflurane-induced reduction of bispectral index does not affect human cerebral microcirculation
New cerebral protection strategies.
PURPOSE OF REVIEW This article presents an overview of the most recent and important strategies to reduce secondary brain damage. RECENT FINDING There is currently no magic bullet available to protect the brain after neuronal injury. This is related to the complex pathophysiology of cerebral ischemia, which makes it unlikely that a single pharmacological intervention results in sustained neuroprotection. Analyses of clinical studies reveal that acute physiologic derangements (e.g. fever, hypertension and hypotension, hypoxemia, hypercapnia, hyperglycemia) are the most important predictors of unfavorable outcome after brain injury and have to be treated. The effectiveness of anesthetic agent…