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Hypothermia and Cerebral Ischemia: Mechanisms and Clinical Applications
Book Reviews
their ®eld, perhaps to consider possible novel approaches, and to understand present thinking. It is certainly extremely valuable from this point of view, representing as it does the best of the presentations at this auspicious meeting. T. Nash Liverpool DOI: 10.1093/bja/aeh543
Hypothermia and Cerebral Ischemia: Mechanisms and Clinical Applications. C. M. Maier and G. K. Steinberg (editors). Published by Humana Press, Totowa, New Jersey. Pp. 188; Indexed; Illustrated. Price US$ 99.50. ISBN 0-86903-660-X. This timely concise textbook, written by a largely American, protagonistic, multi-authorship, heralds resurgence of interest in therapeutic mild hypothermia for cerebral ischaemia in the USA. The book includes contributions from both editors and is written with a preface, list of contents, list of contributors, 10 referenced chapters, and an index. The book comprises an introductory overview, ®ve chapters outlining explanatory and pragmatic experimental hypothermia research, three chapters critiquing pragmatic clinical research studies of brain hypothermia, and a concluding review of hypothermia in clinical practice. Despite the `inevitable' overlap of subject matter found in multi-author, `current review' style textbooks, I found this book well written, referenced and indexed, and adequately illustrated. The reader will ®nd excellent sections outlining some of the history of brain hypothermia research, and the dilemmas faced when trying to carry forward results of pre-clinical, multi-species, multi-model research into the clinical domain. Throughout the book, key differences between studies of mild, moderate, and deep hypothermia are emphasized. The introductory chapter provides a useful and concise `state of the art' overview of the place of hypothermia in brain `protection' for anyone studying for examinations, with the caveat that the book has clearly been written for the US market and therefore retains bias in favour of the hypothermic technique currently prevalent in that domain. Readers lacking background knowledge of current biochemical, in¯ammatory, and histological markers of ischaemic damage and genomics and proteomics may ®nd some sections of the next ®ve chapters devoted to pre-clinical research `hard going'. While the authors are to be congratulated for condensing a vast literature on experimental hypothermia, detailed critique of the numerous preclinical models and markers is sadly lacking. Instead, chapters devoted to experimental focal and global ischaemia and brain trauma overlap to excess, with considerable text devoted to their authors' current research. Concise editing to avoid repetition and devotion of space to explaining the relative merits of different experimental designs and their intended clinical analogues would have greatly enhanced this section of the book and provided ®rmer foundations for subsequent clinical considerations. In stark contrast, later chapters devoted to clinical aspects of hypothermia in intensive care and the operating theatre are easier to read and can stand alone as relevant pre-clinical experimental data are discussed. Dilemmas of when?, where?, how?, how much? and how long? are reasoned concisely and fairly, with repeated frank admission that clinical ef®cacy in brain ischaemia and brain trauma remains unproven. The implications of inconsistencies in clinical trial design and in¯uences of inadequate adherence to trial protocols on trial results are intelligently aired. There is inevitably some overlap of cited literature, with an `American' bias, but the authors retain clarity over its application to the particular clinical setting being discussed. Overall, I enjoyed this short textbook but I am unsure to whom it is primarily aimed. Those familiar with the ®eld may ®nd its
606
Downloaded from http://bja.oxfordjournals.org/ by guest on March 25, 2015
synaptic development of spinal sensory connections is experience or activity dependent. Other topics discussed include the similarity between itch and pain, that muscle central projection C-®bres transmit pain more somato-topically sharply than visceral ®bres, but less so than cutaneous afferents. There are also presentations on brain imaging of visceral sensations, of cognitive modulation of pain, and of a human experimental neuropathic pain model. The section ®nishes with an interesting account of how the placebo effect for analgesia due to the patient's perception of the administration of a treatment is mediated through opioid pathways, and masking its administration can block this effect also. The mechanism of central sensitization is discussed in the fourth section. Amongst other presentations, interesting work is presented on the role of glial cells such as astrocytes and microglia, and their increased activity in exaggerated pain states, as a response to the immune system and in¯ammatory change. There is also discussion of NMDA-receptor-dependent and NMDA-receptor-independent enhancement of pain perception, producing long-term potentiation by high frequency conditioning stimulation, highlighting perhaps the relationship with the conditioning process. The section on pharmacological approaches starts with a discussion on new targets for analgesic drugs, and how progress might be made in the future. The place and pharmacology of cannabinoids, nociceptin, and nocistatin (binding to opioidreceptor-like receptors), and sumatriptan is then discussed. Consideration is given to the side-effects of COX-2 inhibitors and other NSAIDs. The next section is devoted to genetics and gene therapy, with pain sensitivity demonstrated as being familial and heritable. This is followed by clinical epidemiological studies that show that female gender, less than 10 years of education, and high levels of stress at work predispose to chronic pain, and that its incidence is 19% in Denmark. Pain is a problem on standard medical wards, and educational programmes should be instituted for all health care professionals, which cover pain assessment, and the analgesics appropriate for different types of pain. Pain assessment focusing on quantitative and qualitative methods, makes up the next section, together with discussion around pain-related fear being more disabling than pain itself, and the role of self and identity. Speci®c clinical syndromes and settings are the focus of the penultimate section, which opens with yet more basic science approaches in animal models to try to delineate the mechanisms of cancer pain. There is a very good review of the current knowledge of complex regional pain syndromes, and its appropriate treatments. Pain in individuals with developmental disabilities is also discussed, as is phantom limb pain, and acute pain management in the chronic pain sufferer. The use of opioids in chronic non-cancer pain well deserves its place in this section, as does the discussion of the factors involved in pain and aging. Pain in survivors of torture and organized violence brings home a very different aspect of pain in a troubled world, before the discussion on euthanasia and its legal aspects. The book ®nishes with a section on non-pharmacological treatments and outcomes assessment. It focuses on cognitive behavioural treatment, in general, in children and adolescents, and in chronic fatigue syndrome, and presentation of the quantity of evidence now available to support the use of hypnosis for pain. The ®nal two chapters focus on rehabilitation and the injured worker, and then a review of assessment of outcome for rehabilitation. There is a clear absence of any discussion in the book on interventional treatments per se, although mention is made of interventions for complex regional pain syndromes. No great advances in treatment are presented, and this book is clearly for the expert who wishes to access current basic science concepts in
Book Reviews
contents too basic and rather biased in favour of hypothermia. Those with interest in pre-clinical hypothermia research will be cognizant with the hoard of endpoints cited but may desire more detail and a wider reference base to that provided. Clinicians involved in clinical research will immediately sense its `American' perspective and may be disappointed with the rather super®cial way `lessons for the future' are handled. Frankly, there are better reviews on the failings of clinical trial design and protocol implementation in the literature. This book may be of some interest to European intensivists and anaesthetists occasionally working in the ®elds of brain trauma, subarachnoid haemorrhage, ischaemic stroke, and resuscitation who wish to update themselves on current thinking on hypothermia and brain ischaemia. However, given the recent publication of excellent reviews on this subject I could not recommend European readers to purchase this book because of its hefty price. N. M. Dearden Leeds, UK DOI: 10.1093/bja/aeh542 Downloaded from http://bja.oxfordjournals.org/ by guest on March 25, 2015
607
their ®eld, perhaps to consider possible novel approaches, and to understand present thinking. It is certainly extremely valuable from this point of view, representing as it does the best of the presentations at this auspicious meeting. T. Nash Liverpool DOI: 10.1093/bja/aeh543
Hypothermia and Cerebral Ischemia: Mechanisms and Clinical Applications. C. M. Maier and G. K. Steinberg (editors). Published by Humana Press, Totowa, New Jersey. Pp. 188; Indexed; Illustrated. Price US$ 99.50. ISBN 0-86903-660-X. This timely concise textbook, written by a largely American, protagonistic, multi-authorship, heralds resurgence of interest in therapeutic mild hypothermia for cerebral ischaemia in the USA. The book includes contributions from both editors and is written with a preface, list of contents, list of contributors, 10 referenced chapters, and an index. The book comprises an introductory overview, ®ve chapters outlining explanatory and pragmatic experimental hypothermia research, three chapters critiquing pragmatic clinical research studies of brain hypothermia, and a concluding review of hypothermia in clinical practice. Despite the `inevitable' overlap of subject matter found in multi-author, `current review' style textbooks, I found this book well written, referenced and indexed, and adequately illustrated. The reader will ®nd excellent sections outlining some of the history of brain hypothermia research, and the dilemmas faced when trying to carry forward results of pre-clinical, multi-species, multi-model research into the clinical domain. Throughout the book, key differences between studies of mild, moderate, and deep hypothermia are emphasized. The introductory chapter provides a useful and concise `state of the art' overview of the place of hypothermia in brain `protection' for anyone studying for examinations, with the caveat that the book has clearly been written for the US market and therefore retains bias in favour of the hypothermic technique currently prevalent in that domain. Readers lacking background knowledge of current biochemical, in¯ammatory, and histological markers of ischaemic damage and genomics and proteomics may ®nd some sections of the next ®ve chapters devoted to pre-clinical research `hard going'. While the authors are to be congratulated for condensing a vast literature on experimental hypothermia, detailed critique of the numerous preclinical models and markers is sadly lacking. Instead, chapters devoted to experimental focal and global ischaemia and brain trauma overlap to excess, with considerable text devoted to their authors' current research. Concise editing to avoid repetition and devotion of space to explaining the relative merits of different experimental designs and their intended clinical analogues would have greatly enhanced this section of the book and provided ®rmer foundations for subsequent clinical considerations. In stark contrast, later chapters devoted to clinical aspects of hypothermia in intensive care and the operating theatre are easier to read and can stand alone as relevant pre-clinical experimental data are discussed. Dilemmas of when?, where?, how?, how much? and how long? are reasoned concisely and fairly, with repeated frank admission that clinical ef®cacy in brain ischaemia and brain trauma remains unproven. The implications of inconsistencies in clinical trial design and in¯uences of inadequate adherence to trial protocols on trial results are intelligently aired. There is inevitably some overlap of cited literature, with an `American' bias, but the authors retain clarity over its application to the particular clinical setting being discussed. Overall, I enjoyed this short textbook but I am unsure to whom it is primarily aimed. Those familiar with the ®eld may ®nd its
606
Downloaded from http://bja.oxfordjournals.org/ by guest on March 25, 2015
synaptic development of spinal sensory connections is experience or activity dependent. Other topics discussed include the similarity between itch and pain, that muscle central projection C-®bres transmit pain more somato-topically sharply than visceral ®bres, but less so than cutaneous afferents. There are also presentations on brain imaging of visceral sensations, of cognitive modulation of pain, and of a human experimental neuropathic pain model. The section ®nishes with an interesting account of how the placebo effect for analgesia due to the patient's perception of the administration of a treatment is mediated through opioid pathways, and masking its administration can block this effect also. The mechanism of central sensitization is discussed in the fourth section. Amongst other presentations, interesting work is presented on the role of glial cells such as astrocytes and microglia, and their increased activity in exaggerated pain states, as a response to the immune system and in¯ammatory change. There is also discussion of NMDA-receptor-dependent and NMDA-receptor-independent enhancement of pain perception, producing long-term potentiation by high frequency conditioning stimulation, highlighting perhaps the relationship with the conditioning process. The section on pharmacological approaches starts with a discussion on new targets for analgesic drugs, and how progress might be made in the future. The place and pharmacology of cannabinoids, nociceptin, and nocistatin (binding to opioidreceptor-like receptors), and sumatriptan is then discussed. Consideration is given to the side-effects of COX-2 inhibitors and other NSAIDs. The next section is devoted to genetics and gene therapy, with pain sensitivity demonstrated as being familial and heritable. This is followed by clinical epidemiological studies that show that female gender, less than 10 years of education, and high levels of stress at work predispose to chronic pain, and that its incidence is 19% in Denmark. Pain is a problem on standard medical wards, and educational programmes should be instituted for all health care professionals, which cover pain assessment, and the analgesics appropriate for different types of pain. Pain assessment focusing on quantitative and qualitative methods, makes up the next section, together with discussion around pain-related fear being more disabling than pain itself, and the role of self and identity. Speci®c clinical syndromes and settings are the focus of the penultimate section, which opens with yet more basic science approaches in animal models to try to delineate the mechanisms of cancer pain. There is a very good review of the current knowledge of complex regional pain syndromes, and its appropriate treatments. Pain in individuals with developmental disabilities is also discussed, as is phantom limb pain, and acute pain management in the chronic pain sufferer. The use of opioids in chronic non-cancer pain well deserves its place in this section, as does the discussion of the factors involved in pain and aging. Pain in survivors of torture and organized violence brings home a very different aspect of pain in a troubled world, before the discussion on euthanasia and its legal aspects. The book ®nishes with a section on non-pharmacological treatments and outcomes assessment. It focuses on cognitive behavioural treatment, in general, in children and adolescents, and in chronic fatigue syndrome, and presentation of the quantity of evidence now available to support the use of hypnosis for pain. The ®nal two chapters focus on rehabilitation and the injured worker, and then a review of assessment of outcome for rehabilitation. There is a clear absence of any discussion in the book on interventional treatments per se, although mention is made of interventions for complex regional pain syndromes. No great advances in treatment are presented, and this book is clearly for the expert who wishes to access current basic science concepts in
Book Reviews
contents too basic and rather biased in favour of hypothermia. Those with interest in pre-clinical hypothermia research will be cognizant with the hoard of endpoints cited but may desire more detail and a wider reference base to that provided. Clinicians involved in clinical research will immediately sense its `American' perspective and may be disappointed with the rather super®cial way `lessons for the future' are handled. Frankly, there are better reviews on the failings of clinical trial design and protocol implementation in the literature. This book may be of some interest to European intensivists and anaesthetists occasionally working in the ®elds of brain trauma, subarachnoid haemorrhage, ischaemic stroke, and resuscitation who wish to update themselves on current thinking on hypothermia and brain ischaemia. However, given the recent publication of excellent reviews on this subject I could not recommend European readers to purchase this book because of its hefty price. N. M. Dearden Leeds, UK DOI: 10.1093/bja/aeh542 Downloaded from http://bja.oxfordjournals.org/ by guest on March 25, 2015
607