Anesthesia, Evidence and Experience

Residual relaxation, the sleeping brain and anesthesia monitoring: observations on evidence and expectations

Ilkka Kalli, MD, PhD, MBA Senior Lecturer in Medical Informatics, University of Kuopio, Kuopio, Finland; and Consulting Anesthesiologist, Helsinki University Central Hospital, Helsinki, Finland

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Introduction

How do we verify further improvements in the safety of anesthesia when our starting point [1, 2] is already rather good? The major stakeholders in healthcare (patients, physicians and administrators) may have quite different beliefs and expectations as to the impact of new technology on the quality and outcome of care. From the medical science viewpoint, the market mechanism may not be that important. However, in addition to the evidence obtained from medical research, the commercial push-and-pull forces of sales and marketing may also influence how new techniques are adopted. Nevertheless, the good thing is the evolutionary nature of the competition, which is a two-way road. In the late 1980s, for example, lower esophageal contractility was suggested for monitoring the depth of anesthesia, but this is not seen today [3].

Over the last few years, evidence-based medicine (EBM) has become increasingly popular. Pulse oximetry may be a good example of the difficulty of obtaining evidence. When launched on the market more than a decade ago, it was presented as a technology to improve safety and was soon widely accepted. As the early warning tool in routine clinical practice, it seems to work as expected.

However, in a comprehensive systematic review, Pedersen [4] and colleagues found that our current scientific literature is too limited to give evidence in relation to improved reliable outcomes, effectiveness and efficiency. Should we abandon pulse oximetry until there is evidence? Such an approach might be unpractical, as the best currently available knowledge is the practical guideline. In fact, the conclusion of Buhre and Rossaint [1] may be a good closing sentence: "Whether monitoring directly affects outcome is not proven; however, circumstantial evidence suggests that basic cardiorespiratory monitoring decreases the incidence of serious accidents".

Components of anesthesia

Guedel laid the basis for the conceptual theory of general anesthesia in 1937. However, in a few years, neuromuscular blocking agents were introduced to the clinic, and paralyzed patients' traditional clinical signs could not be detected. Thereafter, the number of reports of awareness started increasing. Since then, scientists have further developed the concept of general anesthesia when in 1998 Glass presented his modern hypothesis of general anesthesia [5].

Monitoring of unconsciousness of the brain (sleep) and neuromuscular block (neuromuscular relaxation) are the two main components of anesthesia to which we return in the following paragraphs. Antinociception will be outside the scope of this paper.

The history of neuromuscular block in anesthesia extends for over half a century. Hence, its knowledge base has had time to grow. The modern monitoring of unconsciousness has been available only for a decade. Because of this, the amount of published research on this subject may be more limited.

Neuromuscular relaxation

Neuromuscular blockade has become a routine part of balanced general anesthesia over the past 50 years. As modern surgery gradually progressed, the need for the increased relaxation of muscles became more apparent, e.g. during surgery of the abdominal and pleural cavity. The medical world was slow to accept neuromuscular blocking agents. The work done by Claude Bernard [6] in the mid-19th century finally established the neuromuscular junction as the site of their effect. In the early 20th century, the occasional suggestions made that curare be used as an adjuvant in surgery did not receive much attention. However, reports appeared of its use in the treatment of tetanus [7] and in electroconvulsive therapy [8].

Later, the development of tracheal intubation encouraged experimentation with curare. In 1942, Griffin and Johnson [9] started using curare in a clinical setting. Shortly after, they were supported by Cullen [10]. A decade later, Beecher and Todd [11] questioned the increased rate of anesthesia mortality related to the use of neuromuscular relaxants during surgery. The ensuing debate [12] improved the detection of anesthesia-related risks. The inter-individual variability in drug responses involved an obvious risk of overdosing with muscle relaxants. Gradually the need for objective monitoring of the drug response became important.

The traditional curare-like muscle relaxants were long acting and had marked side effects. Therefore the neuromuscular relaxants with short or intermediate duration of action, lack of cumulation and rapid spontaneous recovery seemed the most suitable for clinical anesthesia. However, they have to be administered as boluses at frequent intervals or as a continuous infusion if adequate muscle relaxation is to be maintained. This requirement stressed the importance of the continuous monitoring of the degree of neuromuscular blockade. Accurate assessment of neuromuscular blockade should improve administration of neuromuscular blocking agents in routine clinical anesthesia, particularly when fast-tracking patients in same-day surgery units.

Monitoring neuromuscular block

In the early days, muscle strength or respiratory parameters were the only guidelines for muscle relaxant administration. They were inaccurate and late indicators of overdosing, which could lead to postoperative residual curarization, respiratory depression and hypoxemia. During surgery, deep neuromuscular blockade combined with a light level of general anesthesia could also result in undetected awareness [13, 14].

Neuromuscular blockade can be monitored by stimulating a peripheral nerve with supramaximal electrical current and then qualifying the response. An important milestone was in 1970, when Ali, Utting and Gray [15] suggested the train-of-four (TOF) stimulation as a standard for monitoring. Monitoring of muscle relaxation subjectively, by visual or tactile assessment or stimulus responses, is only possible during deep levels of blockade. That is not sufficient to ensure proper clinical recovery without residual relaxation [16]. Small piezoelectric transducers fixed near to the thumb allow us to objectively measure recovery up to the full restoration of muscle strength.

Consider a short practical example of laparoscopic sterilization. You have just administered a 30 mg dose of rocuronium, and are waiting for the newest resident gynecologist to enter the OR. However, the consultant comes and completes the case in ten minutes - and the next case is waiting. A neuromuscular monitor may help the anesthetist feel more confident. Such objective monitoring should always be considered when neuromuscular relaxants are used. However, a deep dive into the technicalities of monitoring is outside the scope of this article, and such information can be found in most of the anesthesiology textbooks [17].

Residual neuromuscular block

Overdosing with neuromuscular blocking agents during a light level of anesthesia may result in undetected awareness during surgery. Excessive doses of relaxants may cause residual curarization and postoperative respiratory depression, with an increased risk of pulmonary complications [18, 19]. High inter-individual variability is typical of the effect of neuromuscular blocking agents. Hence there may also be an occasional prolonged effect when using the new intermediate-acting drugs [20].

In the past few years, these new pharmaceuticals have been used to facilitate ventilatory care and to improve the gas exchange of mechanically ventilated, critically ill patients [21]. Myopathy following mechanical ventilation may affect the outcome of a critical care patient. It may have a multi-factorial nature [22], but the role of deep neuromuscular block has also been addressed [23]. Further studies are important to clarify the matter.

The sleeping brain: monitoring unconsciousness

The traditional EEG recording has been available in clinical neurophysiology since 1875. In special circumstances, the neurophysiologist may have been invited to the operating room, but EEG monitoring did not become every anesthesiologist's solution. In all these years, the target of these developments has been to determine the depth of anesthesia [24]. Therefore it may be right to say that modern monitoring of unconsciousness in anesthesia was jump-started when bispectral devices were introduced [25]

In 1998, a publication by Rampil [26] appeared, with an excellent introduction to EEG signal processing. He first presented an extensive review of EEG signal acquisition and the processing methods used in anesthesia. He then moved on to describe how these methods had been applied in the calculation of bispectral index (BIS). The development process and the general architecture of BIS were also described.

The use of BIS has been increasing steadily, as it was the first on the market and its market entry and coordination of validation has been successful. In 2000, Johansen and Sebel published a review article [27] on the development of BIS, and the key studies performed on its validity, performance and clinical utility up until 1999. They also discussed its limitations and potential new applications in pediatric or critical care patients.

Other competing techniques, like monitoring based on the entropy of EEG [28], have recently been introduced. As both BIS [29] and Entropy [30] are new techniques that may have an impact on our future clinical care, studies that show, for example, whether these methods can indicate awareness, optimize care, or influence outcome will be most interesting [31].

Future patient in the flow of information

In the healthcare of the future, patients will be more knowledgeable and they may meet their physician well prepared, having e.g. the same information from Cochrane and EBM sources as the physician has. The traditional patient's role will become one of the consumer, making choices of their own. That puts new demands on the roles of the physicians - some suggest that a future physician should behave more like a coach. Today, health information is widely available from the media and the internet. The quality of web-based health information is enormously variable. A project for certification of health pages on the internet is underway but will take time. Hence the physician as a coach will be an important concept for clarifying the information and expectations that the patients may have.

During preoperative visits many patients may ask questions related to awareness in anesthesia. This indicates the impact of media and television - and the physician needs to be well prepared to give proper answers. In 2003, a systematic review on mass media interventions was included in the Cochrane Database of Systematic Reviews [32]. The paper is interesting as there are not too many of its kind in medical literature. Most likely, a business school background gives a deeper insight into the value of marketing and communication, as these are everyday issues in the business world. In his letter to the Editor of Anesthesiology, Katz [33] emphasized the fact that our patients are regularly exposed to information from the mass media, which may modify their expectations regarding the role of new technology in medicine. Hence further research is the only way to elucidate these matters.

Interestingly, just when I was writing the last few lines of this article, I got a letter from the American Society of Anesthesiologists (ASA) which coincidentally included a fresh sample copy of their brochure on patient awareness. That is an excellent example of targeting correct information right to the patients [34].

Dr. Kalli giving his Clinical Window presentation at the WCA 2004 in Paris.

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Last updated: 26 August 2004 Created
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