Objective : Intracerebral hemorrhage (ICH) is associated with a high mortality. The present study sought to determine the incidence of spontaneous ICH in an intensive care unit (ICU) and associated factors. Design : A 6 year retrospective study. Setting : A general ICU in a university hospital. Patients : All ICU patients developing ICH were included in the study. All trauma and neurosurgical patients were excluded, as well as patients who were admitted to the ICU because of ICH. Measurements and results : During the study period 3032 patients were hospitalized in the ICU, and 834 were excluded. The remaining 2198 patients comprised the study population. Computed tomography of the head was performed in a total of 227 patients, and the 9 patients found to have new onset ICH comprise the group of interest. None of these patients were hypertensive. Seven of the patients had either a primary hematologic malignancy or bone marrow transplantation. Eight had thrombocytopenia of < 100 × 10 9 /l (median 10 × 10 9 /l, range 3–150 × 10 9 /l), and in 6 it preceded ICH by 5 days or more. Only in one patient were both PTT and PT prolonged. All were mechanically ventilated with high peak inspiratory pressure (PIP) (median 37 cmH 2 O, range 20–43 cmH 2 O). Arterial carbon dioxide tension (PaCO 2 ) was considerably elevated (median 65 mmHg, range 41–87 mmHg). All of the patients had impaired renal and hepatic function (urea: median 14 mmol/l, range 9.9–52 mmol/l; bilirubin: median 94 μ mol/l, range 20–360 μ mol/l), and five had septicemia. Eight of the patients bled to other sites before they developed ICH. All patients died shortly after the diagnosis of ICH. Conclusions: Spontaneous nonhypertensive ICH is a rare, fatal event in the ICU. Associated factors include thrombocytopenia, the need for mechanical ventilation, elevated PIP and PaCO 2 , sepsis, and impaired hepatic and renal function.

Objective: To determine whether physicians in Israel withhold and/or withdraw life-sustaining treatments.

When patient or family requests for continued life-sustaining treatments conflict with doctor recommendations, different conclusions as to what is beneficial for the patient may arise. Past practices usually accepted patient or family requests based on the principle of autonomy or that the doctor's primary responsibility is to the individual patient. Many patients die in intensive care units after doctors forego life-prolonging interventions. Health care changes and cost containment have led to a change in the classical ethical model of the patient-doctor relationship such that concerns for societal requirements increasingly overrule those for individual patient needs. The ability to keep patients alive with little likelihood of recovery and the recognition of escalating health costs have led to calls for the needs of society and distributive justice to be taken into account. A tendency to justify a duty to die for these patients has arisen. Recent legal decisions in cases with conflicts between families and health care providers and institutions over foregoing life-sustaining therapies have decided for the families against doctors and hospitals, compelling institutions and their staff to act contrary to their ethical views. Value judgments of doctors are sometimes confused with medical indications for therapy. Doctors have defined therapies as futile or non-beneficial based on their own values and even withdrawn life-sustaining treatments without patient or family input. In some cases, the right to die is leading to the duty to die even against patient or surrogate wishes. Such observations indicate the need for rigorous analyses of medical decision making in this context and for ethical evaluations in health care in general.

OBJECTIVE:To review the literature addressing the issue of a U.S. Food and Drug Administration (FDA) moratorium on use of the pulmonary artery catheter (PAC).DATA SOURCE:Pertinent English language articles dealing with medical devices including the PAC were retrieved from 1976 through 1996.STUDY SELECTION:Articles were chosen if issues related to medical devices were studied or reviewed.DATA EXTRACTION:From the articles selected, information about the 1976 Medical Device Amendment and the PAC was obtained.DATA SYNTHESIS:In 1976, the Medical Device Amendment gave the FDA power over medical devices. The pulmonary artery catheter is considered a class II device and was on the market before passage of the 1976 Act. Class II devices require general and specific controls to reasonably assure safety and effectiveness. A reasonable assurance of safety occurs when the probable benefits to health from the use of the device outweigh any probable risks. If a monitor measures an established and well-understood variable and the intended use claim is limited to the measurement of that variable, then the effectiveness consists of determining device safety and performance defined as the measurement of agreement with a recognized reference method. Deaths and serious injuries secondary to pulmonary artery catheterization are extremely rare despite more than 25 years of use. Pulmonary artery catheter manufacturer's indications for use are measurements such as hemodynamic pressures, thermodilution cardiac output, continuous cardiac output, mixed venous oxygen saturation, and blood sampling; intended uses have not included claims of clinical benefit. Evidence exists that pulmonary artery catheterization provides agreement with established measurements including pressure and cardiac output. Evidence also exists that pulmonary artery catheter derived data are unobtainable clinically, that the derived data helps in therapy changes and may lead to more appropriate therapy. The evidence demonstrates an absence of unreasonable risk of injury from pulmonary artery catheterization and provision of important clinical results. Therefore, pulmonary artery catheterization meets FDA requirements for safety and effectiveness.CONCLUSION:An FDA moratorium on the use of the PAC is not indicated.

OBJECTIVES:To evaluate the timing of foregoing life-sustaining treatments in patients enrolled in a sepsis trial and to determine their influence on patient outcome and trial results.DESIGN:Subset of patients in a prospective, randomized, double-blind, placebo-controlled study.SETTING:Twenty-three academic medical centers.PATIENTS:Enrolled patients who had life-sustaining therapies withheld or withdrawn.MEASUREMENTS AND MAIN RESULTS:The number of patients, types of disorders and interventions, reasons, and timing of withholding and withdrawing life-sustaining treatments and their effect on mortality and trial results were assessed. Foregoing of life-sustaining therapies took place in 117 (22%) of 543 patients and occurred within 72 hrs of study drug administration in 38 (32%) patients. Withholding treatment (60%) was more common than withdrawing treatment (40%), but withdrawing treatment was more frequent (51%) than withholding treatment (20%) in the first 72 hrs of the trial (p < .01). Sixty-one (52%) patients had severe underlying disorders with a poor prognosis. The hospital mortality rate was 94% (of the 117 patients). The mean time (SEM) from withholding or withdrawing of treatment until death was 2.83 +/- 0.57 and 0.32 +/- 0.13 days, respectively (p < .001). Patients who had therapies foregone in the first 24, 48, and 72 hrs after receiving the study drug had higher mortality rates in the first 72 hrs (p < .01).CONCLUSIONS:A substantial number of patients enrolled in a sepsis trial had severe underlying diseases and had foregoing of therapies early in the course of the trial, which led to a higher early mortality rate. Enrollment of patients in clinical trials with severe underlying disorders with a high likelihood of having therapies foregone may bias the potential for showing the efficacy of new therapeutic modalities.

OBJECTIVE:To review the literature addressing ethical issues related to clinical research and the pulmonary artery catheter (PAC).DATA SOURCE:All pertinent English language articles dealing with ethical issues related to clinical research and the PAC were retrieved from 1970 through 1996.STUDY SELECTION:Articles were chosen for review if ethical issues related to clinical research and the PAC were studied or reviewed.DATA EXTRACTION:From the articles selected, information was obtained about the ethics of clinical research related to the PAC.DATA SYNTHESIS:Many current procedures and treatments used on a daily basis have not been proven effective by clinical trials. Studies showing increased mortality with the use of PACs are worrisome. Many clinicians have strong preferences about the use of PACs for various indications and there have been difficulties performing clinical trials. Clinical equipoise occurs when competent physicians are content to have their patients receive any of the various treatments in a randomized trial because, based on available data, none has proven preferable. Clinical equipoise for pulmonary artery catheterization for various indications is unknown. If >70% of experts determine that pulmonary artery catheterization is indicated or contraindicated for specific indications, clinical equipoise does not exist and a trial could not ethically be performed for these indications. Indications and contraindications for pulmonary artery catheterization for these indications, however, should be determined. Clinical equipoise would be present if <70% of experts favor pulmonary artery catheterization for a specific indication and trials could be performed in patients with these disorders.CONCLUSION:Randomized clinical trails of pulmonary artery catheterization can ethically be conducted.

Septic encephalopathy is a reversible dysfunction of the central nervous system (CNS) that develops in seriously ill patients with sepsis. Conditions in which altered mental status results from localized infections of the CNS, such as meningitis, encephalitis and brain abscess, are not considered septic encephalopathy, and so are beyond the scope of this chapter. We will review the manifestations, incidence, etiology, and treatment of septic encephalopathy. In addition, we will review the spectrum of the systemic inflammatory response syndrome (SIRS) and sepsis, based on the American College of Chest Physicians and the Society of Critical Care Medicine (ACCP/SCCM) Consensus Conference Committee statement [1]. This statement came in response to the need for guidelines for sepsis studies and the knowledge that as long as definitions remained ambiguous and controversial, it would be impossible to compare incidence of sepsis, outcome and effect of new therapies in different studies [1–3].

It is becoming increasingly evident that cerebral dysfunction and outcome after severe (i.e., Glasgow Coma Scale — GCS ≤ 8) head injury (SHI) are related, as a rule, not only to the initial structural injury to the brain, but also to a variety of secondary pathophysiological mechanisms, the common denominator of which is ischemia. The ischemic insult apparently initiates several known (and probably many others yet unknown) metabolic/biochemical cascades that are often interacting, and may also, in themselves additionally contribute to the ischemic insult. Many pathways of the injurious pattern had been described and recently reviewed (1–3). Accordingly, reports of improved animal outcome have often appeared which were related to employment of various specific antagonists/competitors/inhibitors to either block, blunt or treat steps in these injurious pathways. The reports from the laboratories leave little doubt as to the relevance of these cascades to the clinical equivalent following SHI in man. Several recent reports have now come from studies in humans that tend to reinforce the evidence from the laboratory. The use of pharmacological agents to prevent, or treat the results of these cascades in humans must still be viewed as experimental at the time these lines are being written. It is not the intention of this presentation to review the extensive research that we and many others had published on the chain of very important events associated with the secondary ischemic injury following SHI.

The optimal surgical treatment for concomitant carotid and coronary artery disease is controversial. Between 1991 and 1995 we performed 34 procedures for combined disease of the carotid and coronary arteries. The first 8 operations were carotid endarterectomies followed by coronary artery bypass grafting (staged procedure). The next 26 operations were performed during a single anesthesia (combined procedure). The patients were 28 men and 6 women, aged 58-81 years (mean 68). 80% were in functional class III or IV. In 40% ventricular function was moderately or severely reduced. There was an average of 3.6 grafts per patient, and in all except 3 patients the left internal thoracic artery was used as a conduit for coronary artery bypass grafting. 30% had symptomatic carotid stenosis; there was no perioperative mortality. In the staged procedure group, 2 patients had postoperative cardiac complications: in 1 acute coronary insufficiency and acute myocardial infarction in the other. 1 had postoperative, transient, amaurosis fugax. In the combined procedure group, 1 had a myocardial infarction and 1 a minor occipital stroke. During follow-up, 1 patient died 4 months after operation of myocardial infarction, and 1 had a minor stroke. The results suggest that the combined procedure is safe and carries low risk of both mortality and morbidity. Whenever cardiac disease is stable and there is no main coronary artery disease, a staged procedure should be considered. In any other situation we continue to perform the combined procedure.

This paper reviews several recent, randomized, double-blind, placebo-controlled trials of monoclonal antibodies against endotoxin, interleukin-1 receptor antagonist (IL-1 ra), and monoclonal antibody against tumor necrosis factor (TNF) in sepsis.