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Ordinarily, when discussing treatment options with a patient, doctors manage to fulfill an ethical obligation by ensuring that the patient's treatment choices are accommodated as far as possible. The four key ethical principles are: beneficence, non-maleficence, respect for autonomy, and justice. One of the cornerstones of good medical practice is that before providing treatment or involving a patient in teaching, or research, doctors must be satisfied that they have a valid authority. Usually this requires the patient to consent to the proposed treatment. In critical care the hardest decisions are those concerning when to withhold or withdraw treatment. Despite this the majority of patients who die in critical care departments do so after a decision to withhold or withdraw life-prolonging care. When considering end-of-life issues, good communication with patients and their relatives is essential for establishing priorities and ensuring that the wishes of the patient are paramount.
The pathophysiology of global ischemia and reperfusion
Tommaso Pellis, The University Laboratory of Physiology, Oxford, UK, Clinical and Medical Affairs, Biosite Incorporated, San Diego, CA, USA,
Jasmeet Soar, The University Laboratory of Physiology, Oxford, UK, Clinical and Medical Affairs, Biosite Incorporated, San Diego, CA, USA,
Gavin Perkins, The University Laboratory of Physiology, Oxford, UK, Clinical and Medical Affairs, Biosite Incorporated, San Diego, CA, USA,
Raúl J. Gazmuri, The University Laboratory of Physiology, Oxford, UK, Clinical and Medical Affairs, Biosite Incorporated, San Diego, CA, USA
The pharmacology of resuscitation is largely based on anecdotal evidence and descriptive research rather than on objective scientific experimentation. Our understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs used to resuscitate victims of cardiac arrest is also limited by ethical and experimental constraints.
Animal models of cardiac arrest and cardiopulmonary resuscitation (CPR), jointly with clinical studies, have considerably increased our understanding of the pathophysiology of cardiac arrest and significantly improved our ability to resuscitate victims of cardiac arrest. The great majority of such studies, however, were designed to address interventions to improve resuscitation rather than to investigate the pharmacological profile of drugs used in settings of cardiac arrest and reperfusion. Even less evidence is available on the PK of administration of multiple drugs, a more complex but realistic scenario. During resuscitative efforts, i.e., low flow reperfusion, significant shunting of blood to vital organs occurs. The use of vasopressors in this setting further modifies the patterns of blood flow distribution, in all likelihood affecting the PK of concomitantly administered drugs.
The time from onset of cardiopulmonary arrest until restoration of an effective spontaneous circulation is the single most important determinant of long-term survival and neurological outcome. Prompt initiation of CPR and defibrillation of ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) are more likely to alter patient outcome than is pharmacologic management. Nevertheless, treatment with pharmacologic agents is frequently required in patients with VF or VT that is refractory to electrical shocks and in patients with asystole or pulseless electrical activity (PEA).
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