Monitoring the brain: processed electroencephalogram and peri‐operative outcomes

Although the brain is the target organ of general anaesthesia, the utility of intra‐operative brain monitoring remains controversial. Ideally, the incorporation of brain monitoring into routine practice would promote the maintenance of an optimal depth of anaesthesia, with an ultimate goal of avoiding the negative outcomes that have been associated with inadequate or excessive anaesthesia. A variety of processed electroencephalogram devices exist, of which the bispectral index is the most widely used, particularly in the research setting. Whether such devices prove to be useful will depend not only on their ability to influence anaesthetic management but also on whether the changes they promote can actually affect clinically important outcomes. This review highlights the evidence for the role of bispectral index monitoring, in particular, in guiding anaesthetic management and influencing clinical outcomes, specifically intra‐operative awareness, measures of early recovery, mortality and neurocognitive outcomes.     

Advances in regional anaesthesia and acute pain management: a narrative review

Regional anaesthesia has undergone several exciting advances in the past few decades. Ultrasound-guided techniques of peripheral nerve blockade have become the gold standard thanks to the associated improvements in efficacy, ease of performance and safety. This has increased the accessibility and utilisation of regional anaesthesia in the anaesthesia community at large and is timely given the mounting evidence for its potential benefits on various patient-centred outcomes, including major morbidity, cancer recurrence and persistent postoperative pain. Ultrasound guidance has also paved the way for refinement of the technical performance of existing blocks concerning simplicity and safety, as well as the development of new regional anaesthesia techniques. In particular, the emergence of fascial plane blocks has further broadened the application of regional anaesthesia in the management of painful conditions of the thorax and abdomen. The preliminary results of investigations into these fascial plane blocks are promising but require further research to establish their true value and role in clinical care. One of the challenges that remains is how best to prolong regional anaesthesia to maximise its benefits while avoiding undue harm. There is ongoing research into optimising continuous catheter techniques and their management, intravenous and perineural pharmacological adjuncts, and sustained-release local anaesthetic molecules. Finally, there is a growing appreciation for the critical role that regional anaesthesia can play in an overall multimodal anaesthetic strategy. This is especially pertinent given the current focus on eliminating unnecessary peri-operative opioid administration.     

Neuroanästhesie

Because of the high vulnerability of the brain as a primary target, neuroanaesthesia requires a close look at basic physiological principles and factors of influence during surgery and subsequent intensive care. Anticipatory management is crucial for anaesthesia within the scope of neurosurgical interventions: essential components of anaesthesia management must already be prepared before the surgical procedure. Intracranial compliance and pressure determine the patient’s fate; accordingly they have to be assessed correctly and measured continuously. Advanced methods of monitoring allow sophisticated and individually focused treatment thus contributing to patient safety. Only few pharmacologic approaches have been proven with solid evidence, yet some new studies have revealed interesting brain protective effects of pharmacological and/or adjuvant therapeutic measures. For the treatment of intracranial hypertension, osmotherapy is still of the highest value. Decompressive craniotomy seems to have become a promising alternative, although this must be judged to date as a last resort therapy. Perioperative care of patients with complex intracranial pathologies thus needs a close interaction and cooperation between the operation theatre and intensive care units in the sense of continuous track anaesthesia.     

General anaesthetics and the developing brain: an overview

Various experimental studies in animals have shown that general anaesthetics are potentially toxic to the developing brain. By inducing apoptosis or interfering with neurogenesis, anaesthetic exposure during a critical period of neuronal development can have significant impact on neurocognitive function later in life. It remains controversial whether these experimental results can be transferred to human beings and this is under intensive scientific evaluation. To gain more insight into possible neurotoxic effects on the human brain of infants and small children, a number of retrospective studies have been performed. At present, there is no clear evidence that exposure to anaesthesia up to the age of 3–4 years is associated with neurocognitive or behavioural deficits. Currently, the PANDA, MASK and GAS studies are underway to explore this relationship. Anaesthesia is not an end in itself, but necessary to facilitate surgical procedures. There is evidence that maintaining physiological conditions is important for the overall outcome following anaesthesia and surgery. Until proven otherwise, it can be recommended to keep anaesthesia and surgery as short as possible, to use short‐acting drugs and/or a combination of general anaesthesia and multimodal pain therapy including systemic analgesics, and local or regional anaesthesia, to reduce the overall drug dosage.     

Anaesthetic management of neurosurgical patients

Anaesthetic care of neurosurgical patients increasingly involves management issues that apply not only to 'asleep patients', but also to 'awake and waking-up patients' during and after intracranial operations. On one hand, awake brain surgery poses unique anaesthetic challenges for the provision of awake brain mapping, which requires that a part of the procedure is performed under conscious patient sedation. Recent case reports suggest that local infiltration anaesthesia combined with sedative regimens using short-acting drugs and improved monitoring devices have assumed increasing importance. These techniques may optimize rapid adjustments of the narcotic depth, providing analgesia and patient immobility yet permitting a swift return to cooperative patient alertness for functional brain tests. Regional anaesthesia and peripheral nerve blocks were used to prevent uncontrolled movements in special cases of intractable seizures. However, few of these strategies have been evaluated in controlled trials. Awake craniotomy for tumour removal is performed as early discharge surgery. Meticulous consideration of postoperative patient safety is therefore strongly advised. On the other hand, waking-up patients or the emergence from general anaesthesia after brain surgery is still an area with considerable variation in clinical practice. Developments indicate that fast-acting anaesthetic agents and prophylactic strategies to prevent postoperative complications minimize the adverse effects of anaesthesia on the recovery process. Recent data do not advocate a delay in extubating patients when neurological impairment is the only reason for prolonged intubation. An appropriate choice of sedatives and analgesics during mechanical ventilation of neurosurgical patients allows for a narrower range of wake-up time, and weaning protocols incorporating respiratory and neurological measures may improve outcome. In conclusion, despite a lack of key evidence to request 'fast-tracking pathways' for neurosurgical patients, innovative approaches to accelerate recovery after brain surgery are needed.     

Regional Anaesthesia in Paediatric Surgery

The use of regional anaesthesia in paediatric surgery remains controversial although the pharmacological and technical aspects, even in this age group, have been described. Many authors regard regional anaesthesia as contra-indicated, and consequently general anaesthesia is preferred in paediatric surgery. In the present study regional anaesthesia was used in the form of supraclavicular, interscalene brachial plexus blockade, axillary brachial plexus blockade, lumbar epidural and spinal blockade in altogether 199 patients in the paediatric age group. Surgically excellent or satisfactory analgesia was achieved in 92-100% of the blocks. No complications were observed.     

Closed loops in anaesthesia

Closed-loop systems are able to make their own decisions and to try to reach and maintain a preset target. As a result, they might help the anaesthetist to optimise the titration of drug administration without any overshoot, controlling physiological functions and guiding monitoring variables. Thanks to the development of fast computer technology and more reliable pharmacological effect measures, the study of automation in anaesthesia has regained popularity. This short review focuses on the most recently developed and tested feedback systems in anaesthesia. Various new approaches for controlling the administration of intravenous and inhaled hypnotic-anaesthetic drugs have recently been published. For analgesics, a framework for further research has been presented in the literature. For other drugs, such as muscle relaxants and haemodynamic agents, only short reviews can be found. Until now, most of these systems have had to be under development. The challenge is now fully to establish the safety, efficacy, reliability and utility of closed-loop anaesthesia so that it can be adopted in the clinical setting. Besides, their role in optimising the controlled variables and control models, these systems have to be tested in extreme circumstances in order to test their robustness.     

A myoclonic seizure during propofol-alfentanil anesthesia?]

Total intravenous anaesthesia with propofol and alfentanil is an established alternative to inhalation anaesthesia for intracranial neurosurgical procedures. Its usefulness has been somewhat overshadowed by reports of seizure-like movements, both during anaesthesia and in the recovery period. These can be related to the use of either anaesthetic agent, but true epileptogenic properties still remain to be demonstrated in man. Opioid-induced rigidity is a well known phenomenon and must not be mistaken for an epileptic seizure. Myoclonic motor activity can be observed even under physiological conditions, e.g. sleep. Almost all anaesthetic agents have been found to produce "epileptic" EEG changes (spikes, polyspikes, spike-wave complexes), but in man these have never been correlated to motor reactions. Propofol's pro- or anticonvulsive action is unclear. While some groups found shortened convulsing times in patients undergoing electroconvulsive therapy with propofol instead of methohexitone, others have reported activation of epileptogenic foci in the EEGs of known epileptic patients. A synergistic effect of propofol and alfentanil in the generation of seizure-like movements cannot be excluded. Whether seizure-like movements indicate a true "epileptogenic potency" of the anaesthetic drugs or are related to other phenomena remains to be studied. Electro-encephalographic monitoring during anaesthesia as well as careful observation and documentation of motor reactions may contribute to elucidation of the problem. We report a case of seizure-like movements during propofol-alfentanil anaesthesia for an elective craniotomy. A 52-year-old patient presented with a history of headaches of increasing frequency. A CT brain scan demonstrated a tumor in the left occipital region.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sédation en réanimation de l'adulte

Sedation in ICU refers to the use of pharmacological or non-pharmacological means, aimed at decreasing the anxiety, ensuring a satisfactory analgesia, minimizing the pain and facilitating airway control and mechanical ventilation. The pharmacological procedure generally depends on the drugs used in anaesthesia. Currently, these drugs are also frequently used in the emergency medicine context and in in- and out-hospital intensive care units. The use of these drugs requires a perfect knowledge of their advantages and disadvantages. Indeed, in ICU, their use is more delicate than in anaesthesia (patients with multiple organ failure, haemodynamic consequences, medical history which is sometimes unknown, etc). The objectives of analgesia and sedation in reanimation, the indications, means and methods of administration have been recalled in a consensus conference as well as in clinical practice recommendations addressed by expert societies. However it remains necessary to adopt an institutional strategy and treat the patient on an individual basis to define the duration, to select the drugs and to determine the degree of sedation. The multi-daily assessment and regular interruption of the administration of the drugs enable a clinical examination of the patient and the closest adaptation to his needs by limiting the side effects. Finally, not all sedations are identical regarding causal or associated diseases. Beyond the simple "auxiliary" sedation, new sedative agents appear to play a specific therapeutic role, hence the term « therapeutic sedation ».     

Gastric disorders: modifications of gastric content,antacids and drugs influencing gastric secretions and motility

Gastric disorders have significant relevance to the fields of both anaesthesia and intensive care medicine. Pneumonitis and development of pneumonia in the perioperative period are significant complications following aspiration of gastric acid and stomach contents. Anaesthetists play a key role in minimizing this risk through careful patient selection, pre-assessment and pharmacological management of gastric acid. Proton pump inhibitors are the most used drug class to reduce the risk of stress-related mucosal damage in intensive care and perioperatively. Histamine-2 receptor antagonists and sucralfate are also effective but not routinely used in clinical practice. Sodium citrate is still commonly used in obstetric anaesthesia. Ventilated patients in intensive care may also suffer from intestinal failure either subsequent to postoperative ileus, pharmacological treatments or as part of multi-organ dysfunction. Many strategies have been proposed for the management of intestinal failure in critical care however evidence is lacking in this area. Prokinetics including metoclopramide and erythromycin remain key drugs in the management of intestinal failure in current practice.     

Alzheimer's disease and anaesthesia: potential relationships and clinical implications

Alzheimer's disease is the most common form of dementia. As the aging population increases, Alzheimer's disease is becoming a major concern of Public Health. Many molecular lesions have been detected in Alzheimer's disease, but physiopathology is still poorly understood. If the neurotoxicity of anaesthetics in human remains debatable, perioperative period is certainly a high-risk factor for cognitive impairment, especially in elderly population. Large clinical studies are required to develop new strategies for perioperative management in such patients, including the adjustment of anaesthesia techniques. Before that, information of patient and its relatives and a particular attention for elderly during anaesthesia and perioperative period should be considered.     

Age-dependent development of acute tolerance to propofol and its distribution in a pharmacokinetic compartment-independent rat model

Background: Previous animal and clinical studies have shown a dose-dependent increase in propofol concentrations in blood at wakening after propofol infusion. A development of an acute tolerance to propofol has been proposed. To elucidate this, brain concentrations of propofol at the time of an EEG end point was used as a measure of CNS sensitivity.
Methods: Twenty young or 20 old rats were assigned to either induction of anaesthesia with propofol or induction followed by maintenance of anaesthesia with intermittent propofol infusions during 60 minutes. All rats were killed at the EEG end point and samples of cerebral cortex, hippocampus, striatum, brain stem, cerebellum, blood, muscle and fat tissue were submitted to HPLC analysis of propofol concentrations. A new model describing the infusion requirements is introduced.
Results: The estimated infusion rate during maintenance declined exponentially with time at a slower rate in young compared with old rats. Old rats had higher propofol concentrations in blood, hippocampus, striatum, brain stem, cerebellum, muscle and fat after 60 minutes compared with induction. In contrast, young animals had no significant change in brain concentrations, but the propofol concentrations in muscle and fat were increased.
Conclusion: It is concluded that maintenance of propofol anaesthesia may alter the CNS sensitivity to propofol in old animals, i.e. an acute tolerance may develop. Young animals do not seem to be capable of developing an acute tolerance to propofol. The results also support previous findings that a redistribution is important for the rapid clearance of propofol from blood.     

Are anaesthetics toxic to the brain?

It has been assumed that anaesthetics have minimal or no persistent effects after emergence from anaesthesia. However, general anaesthetics act on multiple ion channels, receptors, and cell signalling systems in the central nervous system to produce anaesthesia, so it should come as no surprise that they also have non-anaesthetic actions that range from beneficial to detrimental. Accumulating evidence is forcing the anaesthesia community to question the safety of general anaesthesia at the extremes of age. Preclinical data suggest that inhaled anaesthetics can have profound and long-lasting effects during key neurodevelopmental periods in neonatal animals by increasing neuronal cell death (apoptosis) and reducing neurogenesis. Clinical data remain conflicting on the significance of these laboratory data to the paediatric population. At the opposite extreme in age, elderly patients are recognized to be at an increased risk of postoperative cognitive dysfunction (POCD) with a well-recognized decline in cognitive function after surgery. The underlying mechanisms and the contribution of anaesthesia in particular to POCD remain unclear. Laboratory models suggest anaesthetic interactions with neurodegenerative mechanisms, such as those linked to the onset and progression of Alzheimer's disease, but their clinical relevance remains inconclusive. Prospective randomized clinical trials are underway to address the clinical significance of these findings, but there are major challenges in designing, executing, and interpreting such trials. It is unlikely that definitive clinical studies absolving general anaesthetics of neurotoxicity will become available in the near future, requiring clinicians to use careful judgement when using these profound neurodepressants in vulnerable patients.     

Cerebral protection in traumatic brain injury

With advances in the understanding of the pathophysiology of traumatic brain injury, many novel cerebroprotective measures have been developed. Many of them have undergone preclinical trials and have shown promising results, but the results have not translated into clinical benefits. Evidence of these cerebroprotective measures including NMDA‐receptor antagonist, steroids, free radial scavengers, nimodipine, ziconotide, bradykinin receptor antagonist and dexanabinol has been reviewed. Problems encountered in clinical studies of traumatic brain injury are mainly related to the heterogenicity of traumatic brain injury and the design of clinical studies. Given all these difficulties, clear benefit of these measures cannot be shown and an optimum treatment strategy has yet been developed.     

Developmental pharmacology

Growth and maturation characterize the transition of neonates to adults. The physiological changes that children undergo present numerous pharmacological conundrums for the anaesthetist. Extensive changes in drug absorption, protein binding, metabolism and excretion during development result in wide variability in drug disposition. Pharmacodynamic differences and genetic polymorphisms further exacerbate these pharmacokinetic disparities. These changes directly affect drug efficacy and toxicity, and an awareness of this is crucial for clinicians involved in paediatric anaesthesia. Population-based pharmacokinetic-pharmacodynamic modelling provides a novel prospect in paediatric pharmacology research. Modelling has the potential to improve safety in clinical trials and enhance our understanding of drug disposition in vulnerable populations like preterm neonates. Although progress is occurring in developmental pharmacology, gaps remain, and a lot yet remains to be elucidated.     

Perioperativer Einsatz von medizinischer Hypnose

BACKGROUND: Surgical treatment of patients under local anaesthesia is quite commonly restricted by limited compliance from the patient. An alternative to treatment under pharmacological sedation or general anaesthesia could be the application of medical hypnosis. With this method, both suggestive and autosuggestive procedures are used for anxiolysis, relaxation, sedation and analgesia of the patient. PATIENTS AND METHODS: During a 1-year period of first clinical application, a total of 207 surgical procedures on a non-selected collective of 174 patients were carried out under combined local anaesthesia and medical hypnosis. RESULTS: Medical hypnosis proved to be a standardisable and reliable method by which remarkable improvements in treatment conditions for both patient and surgeons were achievable. CONCLUSION: Medical hypnosis is not considered to be a substitute for conscious sedation or general anaesthesia but a therapeutic option equally interesting for anaesthesists and surgeons.     

Prevention of hypotension in spinal anaesthesia carried out for caesarean section

After describing the most commonly applied obstetric indications for caesarean section and the respective percentages reported in countries that are comparable with Italy in terms of health care standards, the clinical reasons and requirements on the basis of which it is considered that spinal anaesthesia is first choice compared to general anaesthesia in obstetrical surgery are outlined. This evidence is confirmed by the spinal anaesthesia/general anaesthesia ratio encountered in the major national and international Obstetric Hospitals. Maternal hypotension remains the most frequent and clinically important complication consequent on spinal anaesthesia in pregnant women at term. The aetiology, frequency and clinical consequences for mother and foetus of severe maternal hypotension and the need to implement effective preventive therapeutic strategies are therefore discussed. The procedures for preventing maternal hypotension are described and for each procedure its validity and standardisation are assessed. It is pointed out that certain procedures have become part of standard practice but their effectiveness has not yet been confirmed while others are not only ineffective but also expose mother and foetus to potential complications. For others again the jury is still out on their real effectiveness. Finally, the techniques that are currently considered to be effective and shared by the majority of authors are described and these must therefore be included in the procedural protocols regarding spinal anaesthesia for caesarean section.     

Neurological consequences after long-term sedation in the ICU

Experiments performed in mammals, including non-human primates, have demonstrated an increase in neuronal death rates normally seen in normal brain development. Such an increase is encountered in diseases but also after exposure of the brain to various class of anaesthetics. In living animals, it can (but not always) result in persistent cognitive impairment. Most of the experiments have been conducted in animals which were never exposed to any pain, which questions their relevancy. On the clinical side, all data comes from retrospective studies. Given the multiple bias, they cannot definitely state that a protocol, if toxic, is more or less when compared to another. Until now, prospective follow-up of children exposed to anaesthetics in utero or during the first months of life do not suggest a major deleterious effect. Yet, a minor one, if existing, would be hard to detect among polluting variables (e.g. pathology requiring anaesthesia, long hospitalization after birth, preterm birth, environmental stress...). For sure, when surgery is mandatory during pregnancy, it is generally for maternal indication and should not be a motif strong enough for foetal extraction, especially in terms where the baby has few chances to survive. Second, it is known for years than anaesthesia before 1 year of age is much riskier than after 1 year, whatever the theorical neurotoxicity is. Third, this enforces the need to develop tools enhancing the precision of anaesthesia as much as possible. Meanwhile, when an infant has undergone numerous general anaesthesias, we strongly recommend a long-time neurological follow-up.     

Anaesthesia and breast-feeding: should breast-feeding be discouraged?

Until a few years ago an interruption of breast-feeding for 12 or even 24 hours was recommended for breast-feeding mothers after anaesthesia, this is no longer valid. If it is the mother's wish, if she is sufficiently awake and physically able, there is no reason not to start breast-feeding a mature and healthy baby immediately after recovery from a general or regional anaesthesia. Even breast-feeding after a Caesarean delivery with administration of the common anaesthetics in the usual (single) doses is no longer considered to be a problem since the amount of the substance taken up from colostrum is vanishingly small in comparison to the amount that is transferred by transplacental routes. Neither the pharmacological properties of the drugs used in association with anaesthesia nor clinical experience justify an interruption of breast-feeding.     

The molecular basis of brain injury and brain edema: the role of oxygen free radicals

This review article outlines basic concepts and pathophysiological aspects of the chemistry of oxygen free radicals in all forms of brain injury and brain edema. Recent experimental studies have demonstrated that oxygen free radicals may be important mediators of brain injury and brain edema, and pharmacological antagonism of oxygen free radicals shows beneficial therapeutic results. A number of fundamental questions need to resolved, and advanced techniques for detecting oxygen free radicals will be needed. No clinical data are available, but oxygen free radical scavengers may possibly become a critical therapeutic modality for brain injury and brain edema.