Molecular & Cellular Biology of Critical Care Medicine – serie

Samuel A. Tisherman, MD', Fritz Sterz, MD~ '~niversit~ of Pittsburgh, Pittsburgh, PA, USA 2~edical University of Vienna, Vienna, Austria The use of hypothermia for a variety of therapeutic purposes has a long and erratic history. Hippocrates recommended the use of topical cooling to stop bleeding. Fay used cooling of the extremities for patients with tumors in the 1930s. It wasn't until the 1950s, when the effects of hypothermia on systemic oxygen metabolism became better defined, that systemic hypothermia became a commonly used modality, particularly for cardiac surgery. Hypothermia was used for protection (treatment before the insult) and preservation (treatment during the insult) of the heart and entire organism during planned operative ischemia. Shortly thereafter, attempts were made to use hypothermia for resuscitation (treatment after the insult) from cardiac arrest and for management of head trauma. At that time, it was felt that moderate hypothermia (28-32OC) was needed. This was difficult to achieve and manage. Multiple complications were noted. Consequently, therapeutic, resuscitative hypothermia lay dormant for many years while mild (32-35°C) to moderate hypothermia became common for many cardiothoracic and neurosurgical procedures. In the early 1990s, it was found that mild hypothermia, even after cardiac arrest, had benefit for the brain. Similar results were found with head trauma. This lead to a burst of enthusiasm for research into resuscitative hypothermia for a variety of insults, most of which have tissue ischemia as a major component.

Acute lung injury (ALI) impacts patient care in every ICU in the world. Our collective understanding of this condition has grown immensely over the last decade of the 20th century, but morbidity and mortality remain unacceptably high. To enhance the understanding of clinicians and researchers, this book addresses the pathophysiology of acute lung injury from a molecular and cellular standpoint; includes animal models of acute lung injury and points to potential therapeutic advances based on scientific findings. It is a concise compendium of the multiple pathways, mechanisms and molecules involved in the pathophysiology of acute lung injury and is intended to help caregivers understand the process and thus care for patients more effectively.

This is the second volume in the book series, "Molecular and Cellular Biology of Critical Care Medicine". In this volume, a group of experts address the molecular and cellular basis of acute brain injury. The text covers acute brain injury within a context relevant to the care of patients with critical neurologic injuries such as cardiac arrest, trauma and stroke. It includes data pertaining to established pathways such as neurotransmission, exitotoxicity, ionic-mechanisms, oxidative stress, inflammation, and cerebral vascular injury. In addition, rapidly developing areas such as cell signaling, adenosine pharmacology, apoptosis, mitochondrial dysfunction, neurocytoskeletal changes, and the role of trophic factors are reviewed from the level of in vitro modeling to human data. Other topics covered that are highly clinically relevant include the effect of genetic background and gender differences in outcome after brain injury, preconditioning, and the effects of currently used anesthetics and sedative agents in patients with brain injury.

Individualized dosing regimens specific to the patient, infection, bacteria, and antibiotic can optimize outcome. Integration of pharmacokinetic and pharmacodynamic data, called dual individualization, can be accomplished through the use of AUIe. AUIC dosing has been shown to predict bacteriological outcomes, hasten clinical outcomes, reduce the emergence of resistance, and be cost-effective. MPC dosing has been shown to predict the emergence of resistant submutants. AUIC and MPC information can provide guidance as to when low doses can be used, and when higher concentrations are required. This strategy can ensure efficacy, minimize toxicity, reduce the opportunity for resistance to occur, and save money. REFERENCES I. Paladino JA. Streamlining antibiotic therapy: clinical application of pharmacokinetic and pharmacodynamic principles. J Osteopath Med 1991; 5: 16-25. 2. Liss RH, Batchelor FR. Economic evaluations of antibiotic use and resistance - a perspective: report of task force 6. Rev Infect Dis 1987; 9 (suppI3): S297-312. 3. Holmberg SO, Solomon SL, Blake PA. Health and economic impacts of antimicrobial resistance. Rev Infect Dis 1987; 9: 1065-78. 4. Sanders cc.Mechanisms responsible for cross-resistance and dichotomous resistance among the quinolones. Clin Infect Dis 2001; 32(Suppl I ):S 1-8. 5. Ballow CH, Schentag 11. Trends in antibiotic utilization and bacterial resistance: report of the NNRSG. Diagn Microbiol Infect Dis. 1992; 15(suppl):37S-42S. 6. Rice LB, Eckstein EC, DeVente J, Shlaes OM. Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center. Clin Infect Dis 1996; 23: 118-24.

Samuel A. Tisherman, MD', Fritz Sterz, MD~ '~niversit~ of Pittsburgh, Pittsburgh, PA, USA 2~edical University of Vienna, Vienna, Austria The use of hypothermia for a variety of therapeutic purposes has a long and erratic history. Hippocrates recommended the use of topical cooling to stop bleeding. Fay used cooling of the extremities for patients with tumors in the 1930s. It wasn't until the 1950s, when the effects of hypothermia on systemic oxygen metabolism became better defined, that systemic hypothermia became a commonly used modality, particularly for cardiac surgery. Hypothermia was used for protection (treatment before the insult) and preservation (treatment during the insult) of the heart and entire organism during planned operative ischemia. Shortly thereafter, attempts were made to use hypothermia for resuscitation (treatment after the insult) from cardiac arrest and for management of head trauma. At that time, it was felt that moderate hypothermia (28-32OC) was needed. This was difficult to achieve and manage. Multiple complications were noted. Consequently, therapeutic, resuscitative hypothermia lay dormant for many years while mild (32-35°C) to moderate hypothermia became common for many cardiothoracic and neurosurgical procedures. In the early 1990s, it was found that mild hypothermia, even after cardiac arrest, had benefit for the brain. Similar results were found with head trauma. This lead to a burst of enthusiasm for research into resuscitative hypothermia for a variety of insults, most of which have tissue ischemia as a major component.

Individualized dosing regimens specific to the patient, infection, bacteria, and antibiotic can optimize outcome. Integration of pharmacokinetic and pharmacodynamic data, called dual individualization, can be accomplished through the use of AUIe. AUIC dosing has been shown to predict bacteriological outcomes, hasten clinical outcomes, reduce the emergence of resistance, and be cost-effective. MPC dosing has been shown to predict the emergence of resistant submutants. AUIC and MPC information can provide guidance as to when low doses can be used, and when higher concentrations are required. This strategy can ensure efficacy, minimize toxicity, reduce the opportunity for resistance to occur, and save money. REFERENCES I. Paladino JA. Streamlining antibiotic therapy: clinical application of pharmacokinetic and pharmacodynamic principles. J Osteopath Med 1991; 5: 16-25. 2. Liss RH, Batchelor FR. Economic evaluations of antibiotic use and resistance - a perspective: report of task force 6. Rev Infect Dis 1987; 9 (suppI3): S297-312. 3. Holmberg SO, Solomon SL, Blake PA. Health and economic impacts of antimicrobial resistance. Rev Infect Dis 1987; 9: 1065-78. 4. Sanders cc.Mechanisms responsible for cross-resistance and dichotomous resistance among the quinolones. Clin Infect Dis 2001; 32(Suppl I ):S 1-8. 5. Ballow CH, Schentag 11. Trends in antibiotic utilization and bacterial resistance: report of the NNRSG. Diagn Microbiol Infect Dis. 1992; 15(suppl):37S-42S. 6. Rice LB, Eckstein EC, DeVente J, Shlaes OM. Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center. Clin Infect Dis 1996; 23: 118-24.

Acute lung injury (ALI) impacts patient care in every ICU in the world. Our collective understanding of this condition has grown immensely over the past decade but morbidity and mortality remain unacceptably high. To enhance the understanding of clinicians and researchers, this book addresses the pathophysiology of acute lung injury from a molecular and cellular standpoint; includes animal models of acute lung injury and points to potential therapeutic advances based on scientific findings. It is a concise compendium of the multiple pathways, mechanisms and molecules involved in the pathophysiology of acute lung injury and is intended to help caregivers understand the process and thus care for patients more effectively.