The goals of this study were to quantify the effects of epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) and CPR with simultaneous chest compression-ventilation and to test the hypothesis that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral and myocardial blood flow were measured by the radiolabeled microsphere technique, which we have previously validated during CPR. We studied the effect of epinephrine on established arterial collapse during CPR with simultaneous chest compression-ventilation with the abdomen bound or unbound. Epinephrine reversed arterial collapse, thereby eliminating the systolic gradient between aortic and carotid pressures and increasing cerebral perfusion pressure and cerebral blood flow while decreasing blood flow to other cephalic tissues. Epinephrine produced higher cerebral and myocardial perfusion pressures during CPR with simultaneous chest compression-ventilation when the abdomen was unbound rather than bound because abdominal binding increased intracranial and venous pressures. In other experiments we compared the effect of epinephrine on blood flow during 1 hr of either conventional CPR or with simultaneous chest compression-ventilation with the abdomen unbound. Epinephrine infusion during conventional CPR produced an average cerebral blood flow of 15 ml/min-100 g (41 + 15% of control) and an average myocardial blood flow of 18 mI/min 100 g (15 ± 8% of control). In our previous studies, cerebral and myocardial blood flow were less than 3 ±+ 1 % of control during conventional CPR without epinephrine. Although flows during CPR with simultaneous chest compression-ventilation without epinephrine were initially higher than those during conventional CPR, arterial collapse developed after 20 min, limiting cerebral and myocardial blood flow. The use of epinephrine throughout 50 min of CPR with simultaneous chest compression-ventilation maintained cerebral blood flow at 22 + 2 ml/min 100 g (73 ± 25% control) and left ventricular blood flow at 38 ± 9 ml/min 100 g (28 ± 8% control). The improved blood flows with epinephrine correlated with improved electroencephalographic activity and restoration of spontaneous circulation. The mechanisms responsible for the increased brain and myocardial blood flow with epinephrine include the prevention of arterial collapse and the intense vasoconstriction of other vascular beds, which prevents the run off of blood into these tissues and preferentially increases cerebral and myocardial perfusion pressures. We conclude that epinephrine substantially improves cerebral and myocardial blood flow during both conventional CPR and CPR with simultaneous chest compression-ventilation and that the combined use of epinephrine and CPR with simultaneous chest compression-ventilation with the abdomen unbound maintains high levels of blood flow to the ...
Few placebo-controlled trials have investigated the treatment of breakthrough pain (BTP) in patients with chronic pain. We evaluated the efficacy and safety of intranasal ketamine for BTP in a randomized, double-blind, placebo-controlled, crossover trial. Twenty patients with chronic pain and at least two spontaneous BTP episodes daily self-administered up to five doses of intranasal ketamine or placebo at the onset of a spontaneous BTP episode (pain intensity > or =5 on a 0-10 scale). Two BTP episodes at least 48 h apart were treated with either ketamine or placebo. Patients reported significantly lower BTP intensity following intranasal ketamine than after placebo (P < 0.0001) with pain relief within 10 min of dosing and lasting for up to 60 min. No patient in the ketamine group required his/her usual rescue medication to treat the BTP episode, while seven out of 20 (35%) patients in placebo group did (P = 0.0135). Intranasal ketamine was well tolerated with no serious adverse events. After ketamine administration, four patients reported a transient change in taste, one patient reported rhinorrhea, one patient reported nasal passage irritation, and two patients experienced transient elevation in blood pressure. A side effect questionnaire administered 60 min and 24 h after drug or placebo administration elicited no reports of auditory or visual hallucinations. These data suggest that intranasal administration of ketamine provides rapid, safe and effective relief for BTP.
This study is an example of a successful physician-directed program to promote more appropriate utilization of health care resources. Cost savings were obtained without any substantial changes in clinical outcomes. Institution of similar practice guidelines should result in pharmaceutical savings in the range of 50% at tertiary care centers around the country, with a slightly smaller degree of savings expected at institutions with more ambulatory surgery.
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