Publications

Vincent, Jean-Louis MD, PhD, FCCM; Navickis, Roberta J. PhD; Wilkes, Mahlon M. PhD Author Information

Nitric oxide (NO) is believed to play a key role in the pathogenesis of septic shock, although many aspects of NO's involvement remain poorly defined. Recent years have seen advances in our understanding of the production and effects of NO, but much of the work has been done in animal models and may not be directly relevant to the clinical situation. Differences between species and models can account for many of the apparently conflicting results obtained. Nevertheless, NO-directed strategies have been developed and tested clinically. However, NO can have both beneficial and detrimental effects on many organ systems in sepsis and attempts to nonselectively block all its actions may therefore not yield positive results on outcome. Further exploration and precision of the role of NO and development of techniques to assess the NO balance in individual patients is necessary before further progress can be made in this field.

Only a small number of acutely ill patients require a PAC and insertion should be individualized based on clinical context, availability of trained staff, and the possibility that measured variables will be able to help guide therapy.

Front cover -- IFC -- Textbook of Critical Care -- Copyright page -- Dedication -- Contributors -- contributors, online chapters -- Preface -- Instructions for online access -- Table of contents -- Online contents -- Part 1: Common Problems in the ICU -- Chapter 1: Sudden Deterioration in Neurologic Status -- ? Impairment in Consciousness -- ? Stroke and Other Focal Neurologic Deficits -- ? Seizures -- ? Generalized Weakness and Neuromuscular Disorders -- ? Neurologic Complications of Procedures and Treatments -- ? Evaluation of Sudden Neurologic Change -- ? Monitoring for Neurologic Changes -- Annotated References -- References -- Chapter 2: Agitation and Delirium -- ? Agitation -- ? Delirium -- ? Pathophysiology -- ? Assessment -- ? Management -- ? Summary -- Annotated References -- References -- Chapter 3: Management of Acute Pain in the Intensive Care Unit -- ? Acute Pain Assessment -- ? Options for Acute Pain Therapy -- Annotated References -- References -- Chapter 4: Fever and Hypothermia -- References -- Chapter 5: Very High Systemic Arterial Blood Pressure -- ? Pathophysiology -- ? Cerebrovascular Disease -- ? Cardiovascular Disease -- ? Renovascular Disease -- ? Excess Catecholamine States -- ? Miscellaneous Conditions -- ? Antihypertensive Medications -- ? Miscellaneous Medications -- ? Summary -- Annotated References -- References -- Chapter 6: Low Systemic Arterial Blood Pressure -- ? Initial Evaluation -- ? What Is the Cause? -- ? Treatment -- Annotated References -- References -- Chapter 7: Tachycardia and Bradycardia -- Annotated References -- References -- Chapter 8: Arterial Hypoxemia -- ? Reduced Alveolar Oxygenation -- ? Diffusion Abnormalities -- ? Ventilation/Perfusion Mismatch -- ? Alveolar-Arterial Partial Pressure of Oxygen Gradient -- ? Reduced Mixed Venous Oxygen -- References -- Chapter 9: Acute Respiratory Failure.

Background Stiripentol (STP) is an antiepileptic drug which efficacy has been demonstrated in severe myoclonic epilepsy and strongly suggested in partial epilepsy as an add-on therapy. A pharmacokinetic (PK) study was performed in healthy volunteers as the linearity of STP PK remains controversial. Methods A randomised double blind cross-over study at 3 different single oral doses (500, 1000, 2000 mg as tablets) was performed in 12 subjects. Sixteen blood samples were collected in each subject. STP plasma concentrations were determined by HPLC. Data were analysed using a compartmental analysis. Results A two-compartment model with a zero order absorption (R0) and a significant lag-time fitted the data. The following parameters were calculated: Cmax (3.1±0.9, 7.1±1.9,13.2±3.6 mg/l), R0 (356±194,742±634, 871±362 mg/h), Cl/F (58±28, 33±10, 25±8 l/h), AUC 0-inf (9.3±3.4, 33.1±10.9, 87.6±27.7 mg.h/l) and T1/2β (4.4±2.1, 10.1±3.3, 13.7±6.2 h) after the 500, 1000 and 2000 mg dosages respectively. Dose-normalized Log10 (AUC) were found significantly different (p< 10−10, ANOVA) between groups. However the half-life was not significantly different between the 1000 and the 2000 mg dosage. Conclusion A dose-dependent non-linear STP PK can be concluded, probably due to an increase in bioavailability, possibly a saturable first-pass effect. However stable concentrations are expected at steady-state as the elimination phase is linear (first order). Clinical Pharmacology & Therapeutics (2005) 77, P64–P64; doi: 10.1016/j.clpt.2004.12.134