London 2003
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Breathing in a Hostile Environment

JS Milledge

 

 

Introduction

The origin of this talk was a look back over forty odd years of research in the field of high altitude physiology and medicine. Rather than a very superficial skate through many expeditions and projects, I have decided to select a few items which have a bearing on the respiratory aspects of the response by the human body to the chronic hypoxia of altitude and which I hope will be of interest to anaesthetists.

 

The Silver Hut Expedition – altitude acclimatization

 

This expedition lasted nine months, in the Everest region of Nepal, included spending the winter of 1960-61 at an altitude of 5,800m in our laboratory hut. We studied the effect of altitude on ourselves and the changes that took place as we acclimatized. My particular project was on the changes in control of breathing and its importance in the process of acclimatization. These changes and the importance of respiratory acclimatization will be discussed. In 1964 the studies were extended to look at differences in control of breathing between Sherpa highlanders and western lowlanders.

 

Erythropoietin, Hb, and altitude

 

The best known, though not the most important, effect of altitude is to increase haemoglobin concentration. In the first few days this is mainly achieved by a reduction in plasma volume. Later the red cell mass is increased due to stimulation of the bone marrow by erythropoietin. We studied the time course of this on an expedition to Mt Kongur in China in 1981. Levels rise quickly on going got altitude but fall to near base line while Hb continues to increase only to rise again if further height is gained.

 

Acute Mountain Sickness (AMS).

 

The mechanisms underlying altitude illness has been the object of much thought and work over the last four decades. We studied the predictive value for AMS of the ventilatory response to hypoxia (HVR) on expeditions to Kenya in 1987 and to Bolivia in 1989. Despite some previous work suggesting that HVR might be important our own and others results indicate that the HVR (at sea level) is not important in determining susceptibility to AMS.

 

Sleep at altitude

 

It is well know that sleep is disturbed and seem to be of poor quality at altitude even in the absence of extraneous problems such as cold or hard lying. I was involved in studying sleep in acclimatized subjects on the American Medical Research Expedition to Everest in 1981. Working in the Western Cwm at 6,300m, periodic breathing (PB) was very obvious and contributes to the many arousals that are a feature of sleep there. The resultant dips in SaO₂ are dramatic. Also on this expedition my colleague Sukhamay Lahiri showed a correlation between HVR and periodic breathing (predicted by control theory). PB requires a brisk HVR so most lowlanders suffer whilst most Sherpas are free of PB.

 

We plan to return to study sleeps at altitude on our forthcoming expedition to the same area of Nepal next month. We will look at both this correlation of HVR to PB and the effect of sleep disruption on cognitive function, using more modern methods than were available in 1981 and on many more subjects.

 

 

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Importance of Solubility to Low Flow Anaesthesia

 

Edmond I Eger II, MD

Professor of Anesthesia and Perioperative Care

University of California, San Francisco

 

 

Although the arguments for low-flow anaesthesia appear to be overwhelming, most anaesthetists have made but tentative moves to adopt this approach.  Most remain "uncomfortable" with low flow delivery.  The discomfort stems in part from a history of the use of higher flow rates and the fear of the "unknown."  In part it stems from a sense of loss of control over the anaesthetic state.  In part it stems from a perception that low flow anaesthesia is a complex approach to anaesthetic delivery that requires a doctoral training in kinetics, engineering, and computer science.

 

Two factors decrease these obstacles to the use of low flow anaesthesia.  Most important is the increasing adoption of the use of anaesthetic monitors that indicate end-tidal anaesthetic concentrations, thereby providing the ability to control anaesthesia on a breath-to-breath basis without regard to inflow rate.   In the absence of such monitors, a second factor, lower solubility, should minimize the concern of the practitioner.

 

Solubility influences the difference between the alveolar concentration of anaesthetic (FA) and the inspired concentration of anaesthetic (FI).  A higher solubility decreases the FA/FI ratio.   When high inflow rates are used, FI approaches the delivered (vaporizer setting) concentration of anaesthetic (FD), and if solubility is low, FA approaches FD because FA approaches FI.  Even a modest solubility (e.g., as with isoflurane) allows a fair approximation of FA from FI or FD.   Low inflow rates introduce another complexity that results from rebreathing of gases partially depleted of anaesthetic.  FI no longer approaches FD.  At a modest or high solubility, FI may differ greatly from FD.  That is, the lower the inflow rate, the greater the impact of rebreathing and a higher anaesthetic solubility.  However, if anaesthetic solubility approaches zero, not only does FA approach FI, but FA approaches FD, even in a low flow system. 

 

Thus, a decrease in solubility minimizes the FA to FD difference, including the difference at low inflow rates, and a low solubility restores the capacity to predict the alveolar anaesthetic concentration from a knowledge of the vaporizer setting.   A low solubility should increase the comfort of the anaesthetist who wishes to use low flow anaesthesia but who doesn't have access

 

Click here for the full text of this lecture in pdf format

 

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 ANAESTHETIC AGENTS AND IMMUNE RESPONSE

Nigel R Webster, Professor of Anaesthesia & Intensive Care, University of Aberdeen, UK.

 

For many years researchers and clinicians have been concerned about the potential impact of anaesthetic agents on immune function. There is a high rate of infections in post-operative patients and there has been demonstrated bone marrow depression after prolonged anaesthetic exposure. Many functions of the immune system are depressed after exposure to the combination of anaesthesia and surgery. It would appear that many of the immune changes seen in surgical patients are primarily the result of the surgical trauma (cautery, tissue and organ manipulation) and endocrine responses (increased ACTH, catecholamines and corticosteroids) as well as ancillary drug effects, rather than the result of anaesthetic exposure itself.

 

Immune consequences of intensive care

Sepsis and septic shock are the commonest causes of mortality on the Intensive Care Unit (ICU). An estimated 400,000 to 500,000 patients develop sepsis each year in European ICUs and some 50% of these demonstrate signs of shock. Sepsis often leads to multi-organ dysfunction (MODS) and failure with an associated high mortality rate. Of those patients developing septic shock some 50-60% will die despite optimum currently available treatment. In addition, it is now appreciated that in many of the patients demonstrating all the signs of classical sepsis no source of infection is found. This condition is referred to as the Systemic Inflammatory Response Syndrome (SIRS). It is thought that this condition results when inflammatory mediators (probably identical to those found in bacteraemic patients) are released from ischaemic and infarcted tissue.

Outcome from sepsis is determined not only by the infection but also by the intensity of the immuno-inflammatory response. This response is essential for the resolution of infection but may occur in an uncontrolled manner causing damage. The pronounced synergy and interaction of the components of the immune system dictate that modulation may result in either immuno-stimulation or immuno-suppression. Co-ordination is therefore vital for an optimum response. Mediators of immunity and inflammation (families of protein and lipid molecules) are part of an intercellular signalling system which allows cells/tissues/organs to take in new information and based on past experience, decide what to do next.

Cytokines

Orchestration of immune and inflammatory responses depends upon communication between cells by soluble molecules given the generic term cytokines, including chemokines, interleukins (IL), growth factors and interferons (IFN). They are low molecular weight secreted proteins which regulate both the amplitude and duration of the immune / inflammatory responses. They have a transient action which is tightly regulated. Cytokines are highly active at very low concentrations, combining with small numbers of high affinity cell surface receptors and producing changes in the patterns of RNA and protein synthesis. Cytokines have multiple effects on growth and differentiation in a variety of cell types with considerable overlap and redundancy between them, partially accounted for by the induction of synthesis of common proteins. Interaction may occur in a variety of ways:

 

·      cascade system in which one cytokine induces another

·      modulation of the receptor of another cytokine

·      either synergism or antagonism of two cytokines acting on the same cell

·      receptor antagonists

·      soluble receptors which bind cytokine without causing a biological action

 

Anaesthesia and the immune response

There is now a substantial body of evidence which demonstrates that opiates and endogenous opioid peptides modulate immune function. Moreover, inflammatory mediators have been shown to modify the release of opioid peptides from both immune system cells and also cells of the peripheral and central nervous system. The potential effects of exogenously administered opioids on the immune system cannot be ignored. Variations in post-operative infection rate has not, to date, been attributed exclusively to the use of peri-operative opioids since there are many other compounding factors. However, it would seem most likely that opioid use in both the surgical patient and the critically ill would have a profound immunomodulatory effect and we should be cognisant of this effect when we chose our anaesthetic, analgesic or sedative technique.

There are well documented effects of anaesthetic agents which have been demonstrated on immune system function in vitro.

·      decreased chemotaxis

·      decreased phagocytic activity

·      depressed neutrophil killing activity

·      decreased cytokine release

·      decreased adhesion molecule formation

·      decreased nitric oxide formation

There are relatively few studies which have looked at the effects of anaesthetic agent on immune function in the clinical situation. It is however, possible that local anaesthesia may be associated with less immune suppression than general anaesthesia.

 

to an end-tidal anaesthetic gas monitor.