Intensive management of patients with severe head injury offers the best hope of minimizing death and functional disability in a young, working population. Secondary neurologic insult can be decreased by cardiorespiratory support and ICP control from the outset. Rapid neurologic assessment, airway management, and support of circulation are the basis of emergency management for head injury. Patients with severe head injury require intensive care management for two major reasons: management of ICP and management of organ system dysfunction. Care should not be withheld because of initially grim (and inaccurate) prognostic assessment. Newer techniques for assessing the adequacy of cerebral circulation may allow refinement of management strategies in the future.

Normal sleep provides a period of physiologically reduced workload for the cardiovascular system for almost one third of the human life span. Snoring, the most common disorder of sleep, heralds the presence of an unstable upper airway and alerts perceptive clinicians to the possibility of OSA. Epidemiologic evidence has implicated snoring as an independent risk factor for the development of hypertension, ischemic heart disease, and cerebral infarction. However, many investigators would attribute these adverse cardiovascular effects to the substantial prevalence of OSA in habitual snorers. The detrimental effects of OSA on hemodynamics and cardiac rhythm have been well documented, and recent data have linked OSA with increased cardiovascular mortality. Worsening hypoxemia during sleep likely contributes to the nocturnal mortality observed in patients with severe COPD. Effective treatment to prevent nocturnal hypoxemia is available for OSA and COPD, with current evidence supporting beneficial effects on survival.

Significant progress has been made recently in the measurement methods and instrumental approaches applicable to bedside testing of critically ill patients. While the "ideal" technology would involve the ability to obtain accurate stat profile values on a continuous basis via noninvasive methods, given the present state of noninvasive sensing technologies, this capability is unlikely to be achieved in the foreseeable future. In principle, invasive and on-line techniques offer more hope for future success in continuous bedside monitoring of all the key critical care analyses. However, success in these directions will come only when issues regarding sensor stability and sampling device/sensor biocompatibility are completely solved. Until then, it appears that the user-friendly point of care type stat analyzers that can provide accurate values for all the key analytes, used in conjunction with existing noninvasive trend monitors (eg, pulse oximetry), will offer the most attractive approach for the effective treatment of critically ill patients.

Unstable angina occurs in a heterogeneous population of patients. In the subset of patients with recent rest angina, both angiographic and angioscopic studies have suggested that coronary artery thrombus is often present and serves as a predictor of subsequent adverse clinical events, including recurrent angina, myocardial infarction, the need for urgent coronary revascularization, and death. Studies of thrombolytic therapy in small populations of patients with unstable angina suggest it may lyse coronary thrombus, raise the ischemic threshold, and possibly have a favorable influence on clinical outcome. Large multicenter trials of patients with unstable angina and non-Q-wave infarction have been designed to answer several questions: Will rt-PA produce improvement in angiographically determined coronary arterial stenoses? Is rt-PA superior to conventional therapy? Is there a need for routine angiography, followed by revascularization, in suitable patients? Until these questions are answered, the role of thrombolytic therapy in patients with unstable angina remains speculative.

The use of thrombolytic therapy has increased considerably in the past five years, particularly in patients with acute myocardial infarction. The agents that have been used in humans thus far include streptokinase and urokinase, as well as tissue-type plasminogen activator and, most recently, single-chain urokinase-type plasminogen activator or pro-urokinase. Each of these agents works by very different mechanisms to activate plasminogen and, as a result, to lyse fibrin clots. This article reviews the mechanisms by which pathophysiologic thrombi develop, the pharmacologic agents available to lyse thrombi, and the mechanisms of action of these agents.

The long-term CVC allows patients with a variety of diseases to lead a more normal and pain-free life. The use of these catheters has become commonplace in most hospitals, and the physician caring for patients in the ICU will be caring for increasing numbers of patients with an indwelling long-term CVC. Infections of these catheters can be manifested in many different ways: tunnel infections, exit site infections, catheter-related bacteremia, and septic thrombophlebitis. The overwhelming majority of these infections are caused by coagulase-negative staphylococci, but physicians should be aware of the wide variety of organisms that can infect the long-term CVC. The diagnosis of long-term CVC sepsis can be difficult, but the use of quantitative blood cultures for catheters left in place and the Maki method for culturing those catheters that are removed will aid physicians in their quest for diagnostic certainty. The great majority of catheter infections will resolve with antibiotic therapy alone without the need for catheter removal, but there are important exceptions to this general rule. Tunnel infections and fungal long-term CVC infections often require catheter removal for their resolution; septic thrombophlebitis and CR-SCVT require the addition of anticoagulation or fibrinolytic therapy to antibiotic regimens for resolution of the infection, and surgical debridement may be warranted if these modalities fail to resolve the infection.

Tissue-type plasminogen activator has high affinity for fibrin and is activated by fibrin. Because of these properties, t-PA was initially expected to cause minimal bleeding complications. This prediction has been only partially confirmed in major clinical trials in which t-PA was given in the doses necessary for effective coronary thrombolysis. The risk of bleeding in patients receiving t-PA is correlated with increased levels of fibrin degradation products and hypofibrinogenemia, consistent with a link between systemic plasminemia and hemorrhage. Limiting t-PA-associated bleeding may therefore require measures aimed at decreasing hyperplasminemia. These measures include a short infusion of a high t-PA dose. This article presents new experimental evidence that has confirmed our previous results showing that a short infusion of t-PA is an effective and safe thrombolytic treatment.

Recombinant tissue-type plasminogen activator (rt-PA), streptokinase (SK), and anisoylated plasminogen-streptokinase activator complex (APSAC) have salutary effects on mortality when administered to patients with evolving acute myocardial infarction (MI). Studies suggest that intravenous rt-PA is more effective in reperfusing occluded infarct-related arteries than SK, and the results of ongoing studies directly comparing the influence of SK and rt-PA on mortality are awaited. The clinical role of agents such as APSAC, urokinase, and pro-urokinase, used alone or in combination, remains to be determined. It is evident that a variety of thrombolytic agents will be effective, and variables such as ease of administration, pharmacokinetics, fibrin specificity, effects on blood viscosity, and incidence of adverse effects need to be assessed to determine which agents are the most suitable for clinical use. There is an increased risk of bleeding at vascular puncture sites with all thrombolytic agents. Current indications for thrombolytic therapy include ischemic chest pain of at least 30 min duration that is unrelieved by nitroglycerin and is associated with ST-segment elevations of at least 0.1 mV in two contiguous electrocardiographic leads. Such therapy is usually reserved for patients less than 75 years old who are not at increased risk for bleeding and whose chest pain began less than 4-6 prior to treatment. Trials are under way to determine whether patients with shorter pain duration, transient ST-segment changes (ie, unstable angina patients), chest pain associated with ST-segment depressions or T-wave inversions (ie, non-Q-wave infarction patients), or patients whose pain began more than 4 to 6 h earlier will benefit from early thrombolytic therapy. Other factors such as patient age, the likelihood of the diagnosis of MI, and the estimated risk of bleeding should also be considered. The findings of available major randomized trials indicate that early invasive procedures are generally unnecessary and that meticulous care must be exercised in the selection and management of patients subjected to thrombolytic therapy.

In most circumstances in health, efficient alveolar ventilation and alveolar-to-arterial exchange of O2 and CO2 are among the strongest of links in the gas-transport chain during maximal exercise. Indeed, in most instances, the metabolic cost of ventilation represents the only significant contribution of the pulmonary system to the limitation of O2 transport of locomotor muscles and thus to the limitation of maximum performance. Of the "weaknesses" inherent in the healthy pulmonary system response to exercise, the most serious one may well be its absence of structural adaptability to physical training or to the trained state. Thus, the lung's diffusion capacity and pulmonary capillary blood volume remain unaltered in the highly trained human or horse, while maximum pulmonary blood flow rises linearly with the enhanced max VO2. Similarly, ventilatory requirement rises markedly, with no alteration in the capability of the airways to produce higher flow rates or of the lung parenchyma to stretch to higher tidal volumes, and little or no change in the pressure-generating capability of inspiratory muscles. The case of the elderly athlete who remains capable of achieving high maximum pulmonary blood flows and ventilatory requirements and whose lung undergoes a normal aging process underscores the importance of deficits (from "normal") on the capacity end of this continuum of cost versus capacity in the pulmonary system. The asthmatic athlete may represent another such example of limited flow-generating capacity; and the healthy, young, highly fit athlete who shows marked reductions in SaO2 and in max VO2 at even moderately high altitudes demonstrates that, in many situations, precious little room can be added to the demand side or removed from the capacity side before signs of failure can be seen.

Breathing is controlled by an automatic brain-stem controller acted on by higher neural influences that stabilize breathing and compensate for neuromechanical abnormalities. Loss of this wakefulness-dependent descending influences during nonrapid eye movement (NREM) sleep results in the appearance of a hypocapnic apnea threshold, which is associated with periodic breathing when the gain of chemical feedback loops is high. In addition, loss of the descending wakefulness influence leads to loss of motor compensation that results in a rise in upper airway resistance, obstructive sleep apnea or hypoventilation in patients with kyphoskoliosis or thoracic neuromuscular disorders. REM sleep poses different problems for the respiratory control system owing to muscular atomia and suppression of chemical feedback. These changes are associated with respiratory deterioration in patients with compromised diaphragmatic function, eg, patients with chronic obstructive pulmonary disease.