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Biomedical subjects

M J Breslow

Publications and source records attributed to M J Breslow.

At least 19 recordsLinked to original sources
PubMed1999

Organizational characteristics of intensive care units related to outcomes of abdominal aortic surgery.

CONTEXT: Morbidity and mortality rates in intensive care units (ICUs) vary widely among institutions, but whether ICU structure and care processes affect these outcomes is unknown. OBJECTIVE: To determine whether organizational characteristics of ICUs are related to clinical and economic outcomes for abdominal aortic surgery patients who typically receive care in an ICU. DESIGN: Observational study, with patient data collected retrospectively and ICU data collected prospectively. SETTING: All Maryland hospitals that performed abdominal aortic surgery from 1994 to 1996. PATIENTS AND PARTICIPANTS: We analyzed hospital discharge data for patients in non-federal acute care hospitals in Maryland who had a principal procedure code for abdominal aortic surgery from January 1994 through December 1996 (n = 2987). We obtained information about ICU organizational characteristics by surveying ICU medical directors at the 46 Maryland hospitals that performed abdominal aortic surgery. Thirty-nine (85%) of the ICU directors completed this survey. MAIN OUTCOME MEASURES: In-hospital mortality and hospital and ICU length of stay. RESULTS: For patients undergoing abdominal aortic surgery, in-hospital mortality varied among hospitals from 0% to 66%. In multivariate analysis adjusted for patient demographics, comorbid disease, severity of illness, hospital and surgeon volume, and hospital characteristics, not having daily rounds by an ICU physician was associated with a 3-fold increase in in-hospital mortality (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.9-4.9). Furthermore, not having daily rounds by an ICU physician was associated with an increased risk of cardiac arrest (OR, 2.9; 95% CI, 1.2-7.0), acute renal failure (OR, 2.2; 95% CI, 1.3-3.9), septicemia (OR, 1.8; 95% CI, 1.2-2.6), platelet transfusion (OR, 6.4; 95% CI, 3.2-12.4), and reintubation (OR, 2.0; 95% CI, 1.0-4.1). Not having daily rounds by an ICU physician, having an ICU nurse-patient ratio of less than 1:2, not having monthly review of morbidity and mortality, and extubating patients in the operating room were associated with increased resource use. CONCLUSIONS: Organizational characteristics of ICUs are related to differences among hospitals in outcomes of abdominal aortic surgery. Clinicians and hospital leaders should consider the potential impact of ICU organizational characteristics on outcomes of patients having high-risk operations.

Aged↗
PubMed1999

The stress response of critical illness.

The integrated stress response to tissue trauma is crucial for the maintenance of homeostasis. An exaggerated or prolonged response may be detrimental in compromised patients. Knowledge of the involved afferent pathways will suggest therapeutic interventions that may modulate the intensity of the stress response. Described are these concepts as they relate to perioperative medicine.

Afferent Pathways↗
PubMed1999

Effect of leptin deficiency on metabolic rate in ob/ob mice.

Reduced metabolic rate may contribute to weight gain in leptin-deficient (ob/ob) mice; however, available studies have been criticized for referencing O2 consumption (VO2) to estimated rather than true lean body mass. To evaluate whether leptin deficiency reduces energy expenditure, four separate experiments were performed: 1) NMR spectroscopy was used to measure fat and nonfat mass, permitting VO2 to be referenced to true nonfat mass; 2) dietary manipulation was used in an attempt to eliminate differences in body weight and composition between ob/ob and C57BL/6J mice; 3) short-term effects of exogenous leptin (0.3 mg. kg-1. day-1) on VO2 were examined; and 4) body weight and composition were compared in leptin-repleted and pair-fed ob/ob animals. ob/ob animals had greater mass, less lean body mass, and a 10% higher metabolic rate when VO2 was referenced to lean mass. Dietary manipulation achieved identical body weight in ob/ob and C57BL/6J animals; however, despite weight gain in C57BL/6J animals, percent fat mass remained higher in ob/ob animals (55 vs. 30%). Exogenous leptin increased VO2 in ob/ob but not control animals. Weight loss in leptin-repleted ob/ob mice was greater than in pair-fed animals (45 vs. 17%). We conclude, on the basis of the observed increase in VO2 and accelerated weight loss seen with leptin repletion, that leptin deficiency causes a reduction in metabolic rate in ob/ob mice. In contrast, these physiological studies suggest that comparison of VO2 in obese and lean animals does not produce useful information on the contribution of leptin to metabolism.

Animals↗
PubMed1998

Beta-adrenergic blockade accelerates conversion of postoperative supraventricular tachyarrhythmias.

BACKGROUND: Postoperative supraventricular tachyarrhythmia is a common complication of surgery. Because chemical cardioversion is often ineffective, ventricular rate control remains a principal goal of therapy. The authors hypothesized that patients with supraventricular tachyarrhythmia after major noncardiac surgery who receive intravenous beta-adrenergic blockade for ventricular rate control would experience conversion to sinus rhythm at a rate that differs from those receiving intravenous calcium channel blockade. METHODS: The rate of conversion to sinus rhythm at 2 and 12 h after treatment was examined in 64 cases of postoperative supraventricular tachyarrhythmia. After adenosine administration, patients who remained in supraventricular tachyarrhythmia were prospectively randomized to receive either intravenous diltiazem or intravenous esmolol for ventricular rate control (unblinded). Loading and infusion rates were adjusted to achieve equivalent degrees of ventricular rate control. RESULTS: Patients were similar with regard to age and Apache III score. Most patients in both groups had atrial fibrillation (esmolol, 79%; diltiazem, 81%), and none experienced stable conversion with adenosine. Patients randomized to receive esmolol experienced a 59% rate of conversion to sinus rhythm within 2 h of treatment, compared with only 33% for patients randomized to receive diltiazem (intention to treat, P = 0.049; odds ratio, 2.9; 95% confidence interval, 1.046 to 7.8). After 12 h of therapy, the number of patients converting to sinus rhythm increased in both groups (esmolol, 85%; diltiazem, 62%), and the rates of conversion no longer differed significantly. Ventricular rates when supraventricular tachyarrhythmia began and after 2 and 12 h of rate control therapy were similar in the two treatment groups. The in-hospital mortality rate and length of stay in the intensive care unit were not significantly influenced by treatment group. CONCLUSIONS: Among adenosine-resistant patients in the intensive care unit with atrial fibrillation after noncardiac surgery, intravenous esmolol produced a more rapid (2-h) conversion to sinus rhythm than did intravenous diltiazem.

Adrenergic beta-Antagonists↗
PubMed1998

"Renal dose" dopamine in surgical patients: dogma or science?

OBJECTIVE: "Renal dose" dopamine is widely used in the perioperative period to provide renal protection. A comprehensive review of the literature was performed to determine whether dopamine does in fact confer protection on the kidneys of surgical patients. SUMMARY BACKGROUND DATA: Studies in healthy animals and human volunteers reveal that dopamine causes diuresis and natriuresis, as well as some degree of renal vasodilatation. RESULTS: Studies of the perioperative use of dopamine fail to demonstrate any benefit of dopamine in preventing renal failure. Studies in congestive heart failure, critical illness, and sepsis also fail to show any benefit of dopamine other than diuresis. Further, dopamine administration is not completely without risk, because of dopamine's catecholamine and neuroendocrine functions. CONCLUSIONS: Routine use of prophylactic "renal dose" dopamine in surgical patients is not recommended.

Animals↗
PubMed1998

Radial artery pressure monitoring underestimates central arterial pressure during vasopressor therapy in critically ill surgical patients.

OBJECTIVES: Radial artery pressure is known to differ from central arterial pressure in normal patients (distal pulse amplification) and in the early postcardiopulmonary bypass period. The adequacy of the radial artery as a site for blood pressure monitoring in critically ill patients receiving high-dose vasopressors has not been carefully examined. DESIGN: Prospective observational study comparing simultaneous intra-arterial measurements of radial (peripheral) and femoral artery (central) pressures. SETTING: Clinical investigation in a university-based surgical intensive care unit. PATIENTS: Fourteen critically ill patients with presumed sepsis who received norepinephrine infusions at a rate of > or =5 microg/min. INTERVENTIONS: All patients were managed in accordance with our standard practice for presumed sepsis, which consisted of intravascular volume repletion followed by vasopressor administration titrated to a mean arterial pressure of > or =60 mm Hg. MEASUREMENTS AND MAIN RESULTS: Systolic and mean arterial pressures were significantly higher when measured from the femoral vs. radial site (p < .005). The higher mean arterial pressures enabled an immediate reduction in norepinephrine infusions in 11 of the 14 patients. No change in cardiac output or pulmonary artery occlusion pressure was noted after dose reduction. In the two patients in whom simultaneous recordings were made after discontinuation of norepinephrine infusions, equalization of mean arterial pressures was observed. CONCLUSIONS: Radial artery pressure underestimates central pressure in hypotensive septic patients receiving high-dose vasopressor therapy. Clinical management, based on radial pressures, may lead to excessive vasopressor administration. Awareness of this phenomena may help minimize adverse effects of these potent agents by enabling dosage reduction.

Bias↗
PubMed1997

Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. A randomized clinical trial.

OBJECTIVE: To assess the relationship between body temperature and cardiac morbidity during the perioperative period. DESIGN: Randomized controlled trial comparing routine thermal care (hypothermic group) to additional supplemental warming care (normothermic group). SETTING: Operating rooms and surgical intensive care unit at an academic medical center. SUBJECTS: Three hundred patients undergoing abdominal, thoracic, or vascular surgical procedures who either had documented coronary artery disease or were at high risk for coronary disease. OUTCOME MEASURE: The relative risk of a morbid cardiac event (unstable angina/ischemia, cardiac arrest, or myocardial infarction) according to thermal treatment. Cardiac outcomes were assessed in a double-blind fashion. RESULTS: Mean core temperature after surgery was lower in the hypothermic group (35.4+/-0.1 degrees C) than in the normothermic group (36.7+/-0.1 degrees C) (P<.001) and remained lower during the early postoperative period. Perioperative morbid cardiac events occurred less frequently in the normothermic group than in the hypothermic group (1.4% vs 6.3%; P=.02). Hypothermia was an independent predictor of morbid cardiac events by multivariate analysis (relative risk, 2.2; 95% confidence interval, 1.1-4.7; P=.04), indicating a 55% reduction in risk when normothermia was maintained. Postoperative ventricular tachycardia also occurred less frequently in the normothermic group than in the hypothermic group (2.4% vs 7.9%; P=.04). CONCLUSION: In patients with cardiac risk factors who are undergoing noncardiac surgery, the perioperative maintenance of normothermia is associated with a reduced incidence of morbid cardiac events and ventricular tachycardia.

Aged↗
PubMed1997

Beta-3 adrenoceptor (beta-3AR) expression in leptin treated OB/OB mice.

Leptin-deficient Ob/Ob mice are hypometabolic and have reduced fat cell expression of beta-3 adrenoceptors (ARs). To determine whether leptin repletion restores beta-3 AR number, C57BL/6J Ob/Ob mice were given exogenous leptin (5 mg/kg I.P. daily) for 21 days. Leptin administration reduced body weight from 43.1+/-3.7 to 34.1+/-3.7 g in Ob/Ob animals but had no effect on weight in wildtype animals. Body weight increased by 12% in Ob/Ob mice receiving saline. Beta-3 AR mRNA concentrations were markedly reduced in Ob/Ob animals at baseline. Leptin increased beta-3 AR mRNA to control levels in Ob/Ob mice, but had no effect in wildtype animals. Adipocyte leptin mRNA was increased by 400% in Ob/Ob mice and did not suppress with exogenous leptin administration, suggesting no direct feedback regulation of leptin synthesis. We speculate that restoration of beta-3 AR expression by repleting leptin may be important in correcting hypometabolism in Ob/Ob animals.

Animals↗
PubMed1997

Effects of clonidine on prolonged postoperative sympathetic response.

OBJECTIVE: Surgical trauma results in diffuse sympathoadrenal activation which is thought to contribute to perioperative cardiovascular complications in high-risk patients. Regional anesthetic and analgesic techniques can attenuate this "stress response" and reduce the occurrence rate of adverse perioperative events; however, their use in the postoperative period is logistically difficult and costly. The present study was undertaken to evaluate whether transdermal administration of the alpha2 adrenergic-receptor agonist, clonidine, can be used as a pharmacologic means of blunting the stress response throughout the perioperative period. DESIGN: Double-blind, placebo-controlled clinical trial in patients undergoing pancreatico-biliary surgery. SETTING: Operating rooms and surgical intensive care unit of a major university teaching hospital. PATIENTS: Forty patients scheduled for major upper abdominal surgery. INTERVENTIONS: Patients received either clonidine (0.2 mg orally and a clonidine TTS-3 patch the evening before surgery and 0.3 mg orally on call to the operating room) or matched oral and transdermal placebo. MEASUREMENTS AND MAIN RESULTS: Heart rate, systemic arterial blood pressure, plasma catecholamine, clonidine, interleukin-6 concentrations, and 24-hr urine cortisol and nitrogen excretion were measured the day before surgery and daily thereafter for 72 hrs postoperatively. Preoperative transdermal (and oral) clonidine administration resulted in therapeutic plasma clonidine concentrations throughout the perioperative period (1.54 +/- .07 [SEM] microg/mL). Clonidine reduced preoperative epinephrine and norepinephrine concentrations by 65%. Plasma catecholamine concentrations increased in both groups following surgery but were markedly lower throughout the postoperative period in patients receiving clonidine. Patients receiving clonidine had a reduced frequency rate of postoperative hypertension. Clonidine had no effect on plasma interleukin-6 concentration, urine cortisol excretion, or urine nitrogen excretion. No adverse effects of clonidine administration were observed. CONCLUSIONS: The combined administration of oral and transdermal clonidine effectively attenuated the catecholamine response to surgical stress throughout the postoperative study period. Clonidine administration produced specific sympatholytic effects, since other elements of the stress response were not attenuated. Undesirable side effects were not noted. The sustained sympatholytic effects we observed suggest that alpha2 adrenergic-receptor agonists may offer a pharmacologic means of modifying the sympathoadrenal response to injury, and may be useful in reducing perioperative complications.

Administration, Cutaneous↗
PubMed1997

Adrenergic, respiratory, and cardiovascular effects of core cooling in humans.

The adrenergic, respiratory, and cardiovascular responses to isolated core cooling were assessed in awake human subjects. Mild core hypothermia was induced by intravenous infusion of 30 or 40 ml/kg of cold saline (4 degrees C) on 2 separate days. A warm intravenous infusion (30 ml/kg, 37 degrees C) was given on a third day as a control treatment. Mean norepinephrine concentration increased 400% and total body oxygen consumption increased 30% when core temperature decreased 0.7 degrees C. Mean norepinephrine concentration increased 700% and total body oxygen consumption increased 112% when core temperature decreased 1.3 degrees C. Core cooling was associated with peripheral vasoconstriction and increased mean arterial blood pressure, whereas heart rate was unchanged. Plasma epinephrine and cortisol concentrations were unchanged during core cooling. There were no changes in any measured parameter with the warm infusion. These findings suggest that mild hypothermia induced by isolated core cooling is associated with an adrenergic response characterized by peripheral sympathetic nervous system activation without a significant adrenocortical or adrenomedullary response. The respiratory and cardiovascular responses to core cooling are characterized by a shivering-induced increase in metabolic rate, norepinephrine-mediated peripheral vasoconstriction, and increased arterial blood pressure.

Adolescent↗
PubMed1996

Effect of hemocarboperfusion on organ blood flow and survival in porcine endotoxic shock.

OBJECTIVE: To evaluate the effects of hemocarboperfusion on hemodynamics, organ blood flow, and survival in endotoxin shock. DESIGN: Prospective, placebo-controlled, animal trial. SETTING: Research laboratory in a major university teaching hospital. SUBJECTS: Pentobarbital-anesthetized pigs. INTERVENTIONS: Twenty-eight pentobarbital-anesthetized pigs (18.5 to 22.3 kg) received 100 micrograms/kg of Escherichia coli endotoxin (lipopolysaccharide 0127) over 30 mins. Group 1 animals (n = 14) were controls and had blood diverted through an extracorporeal circuit without activated charcoal for 60 mins after lipopolysaccharide infusion. Group 2 animals (n = 14) underwent nonpulsatile hemocarboperfusion (activated charcoal SCN-1K). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, cardiac output, systemic vascular resistance, mean pulmonary arterial pressure, pulmonary vascular resistance, oxygen delivery, and regional blood flow (radiolabeled microsphere technique) were determined at baseline and every 30 mins for 150 mins. Results are presented as mean +/- SD. Parameters in the two groups were compared by two-way analysis of variance. A p < .05 was considered significant. The survival rate was ten (71%) of 14 animals in group 1 compared with 14 (100%) of 14 animals in group 2 (p < .05, Fisher's exact test). The mean cardiac output at the end of hemocarboperfusion was 1.6 +/- 0.6 L/min in group 1 compared with 3.0 +/- 0.9 L/min in group 2, and remained lower in group 1 animals throughout the experiment. Pulmonary arterial pressure and pulmonary vascular resistance were lower in the hemocarboperfusion-treated animals during and after hemocarboperfusion. Systemic vascular resistance increased by 70% after lipopolysaccharide infusion and returned to baseline values in the hemocarboperfusion group but remained increased in controls. Oxygen delivery was lower in group 1 at 90 and 150 mins (287 +/- 34 vs. 478 +/- 48 mL/min and 251 +/- 24 vs. 356 +/- 21 mL/min, respectively). Blood flow rates to the brain (38.5 +/- 7.5 vs. 27.1 +/- 5.4 mL/min/100 g), large intestine (26.6 +/- 1.1 vs. 17.7 +/- 2.5 mL/ min/100 g), and adrenal cortex (200 +/- 45 vs. 139 +/- 41 mL/min/100 g) were higher in the hemocarboperfusion group at the completion of carboperfusion but not at later time points. CONCLUSION: These data suggest that hemocarboperfusion may be of value in the treatment of septic shock.

Animals↗
PubMed1995

The catecholamine, cortisol, and hemodynamic responses to mild perioperative hypothermia. A randomized clinical trial.

BACKGROUND: Unintended hypothermia occurs frequently during surgery and may have adverse effects on the cardiovascular system. Although the mechanisms responsible for the cardiovascular manifestations of hypothermia are unclear, it is possible that they are sympathetically mediated. In this prospective study, relationships between body temperature, the neuroendocrine response, and hemodynamic changes in the perioperative period were examined. METHODS: Seventy-four elderly patients, undergoing abdominal, thoracic, or lower extremity vascular surgical procedures, were randomly assigned to either "routine care" (n = 37) or "forced-air warming" (n = 37) groups. Throughout the intraoperative and early postoperative periods, the routine care group received standard thermal care, and the forced-air warming group received forced-air skin-surface warming. Core temperature, forearm minus fingertip skin-surface temperature gradient, and plasma concentrations of epinephrine, norepinephrine, and cortisol were measured throughout the perioperative period, and the two groups were compared. In addition, heart rate and arterial blood pressure were compared between groups. RESULTS: The routine care and forced-air warming groups did not differ with regard to age, sex, type of surgical procedures, anesthetic techniques, or postoperative analgesia. Mean core temperature was lower in the routine care group on admission to the postanesthetic care unit (routine care, 35.3 +/- 0.1 degree C; forced-air warming, 36.7 +/- 0.1 degree C; P = 0.0001) and remained lower during the early postoperative period. Forearm minus fingertip skin-surface temperature gradient (an index of peripheral vasoconstriction) was greater in the routine care group in the early postoperative period. The mean norepinephrine concentration (pcg/ml) was greater in the routine care group immediately after surgery (480 +/- 70 vs. 330 +/- 30, P = 0.02) and at 60 min (530 +/- 50 vs. 340 +/- 30, P = 0.002) and 180 min (500 +/- 80 vs. 320 +/- 30, P = 0.004) postoperatively. Mean epinephrine concentrations were not significantly different between groups. Mean cortisol concentrations were increased in both groups during the early postoperative period (P < 0.01), but the differences between groups were not significant. Systolic, mean, and diastolic arterial blood pressures were significantly higher in the routine care group. CONCLUSIONS: Compared with patients in the forced-air warming group, patients receiving routine thermal care had lower core temperatures, a greater degree of peripheral vasoconstriction, higher norepinephrine concentrations, and higher arterial blood pressures in the early postoperative period. These findings suggest a possible mechanism for hypothermia-related cardiovascular morbidity in the perioperative period.

Aged↗
PubMed1995

Multivariate determinants of early postoperative oxygen consumption in elderly patients. Effects of shivering, body temperature, and gender.

BACKGROUND: Previous investigators have proposed that postoperative shivering may be poorly tolerated by patients with cardiopulmonary disease because of the associated significant increase in total-body oxygen consumption. However, the often-quoted 300-400% increase in oxygen consumption with shivering was derived from relatively few studies performed in a small number of younger persons specifically selected on the basis of clinically recognizable shivering. We hypothesized that the average elderly postoperative patient has a shivering response that is associated with a relatively small increase in total-body oxygen consumption. METHODS: One hundred eleven elderly patients (age > 60 yr) undergoing surgery were studied to assess the determinants of shivering and total-body oxygen consumption in the early postoperative period. Anesthetic technique, postoperative analgesia, and thermal management were controlled by protocol. The clinical variables associated with shivering and increased total-body oxygen consumption were determined by univariate and multivariate analyses. RESULTS: Mean total-body oxygen consumption in shivering patients was 38% greater than in nonshivering patients. Regardless of whether data from shivering patients were included in the analysis, oxygen consumption was directly proportional to mean body temperature. Despite similar core temperatures, men had a greater incidence of clinically recognizable shivering and greater total-body oxygen consumption than did women. CONCLUSIONS: The metabolic demands associated with postoperative shivering in elderly patients are less than those reported previously in younger persons. These findings suggest that if hypothermia predisposes to cardiovascular complications in the postoperative period, these complications are not likely to be mediated by shivering and increased metabolism.

Aged↗
PubMed1995

Catecholamine and cortisol responses to lower extremity revascularization: correlation with outcome variables. Perioperative Ischemia Randomized Anesthesia Trial Study Group.

OBJECTIVE: To determine whether catecholamine and cortisol secretory responses to surgery contribute to postoperative complications. DESIGN: Prospective, randomized, case series. SETTING: A university hospital operating suite and surgical intensive care unit. PATIENTS: Sixty patients undergoing lower extremity vascular surgery. INTERVENTIONS: Patients were randomized to receive either epidural anesthesia/epidural opiate analgesia (regional anesthesia) or general anesthesia/intravenous patient-controlled analgesia (general anesthesia). MEASUREMENTS AND MAIN RESULTS: Anesthesia was managed according to a prospectively designed protocol. Hemodynamic parameters and plasma catecholamine concentrations were determined at specific intraoperative and postoperative time points. Intraoperative and postoperative urine samples were collected and analyzed for free cortisol concentrations. Outcomes evaluated were cardiac (nonfatal myocardial infarction and cardiac death) and surgical (graft occlusion). Mean arterial pressure during emergence from anesthesia and in the early postoperative period correlated positively with plasma norepinephrine concentration (p < .01). In addition, plasma catecholamine concentrations were higher in patients with postoperative hypertension. Plasma norepinephrine concentrations at the time of emergence from anesthesia and postoperatively were also higher in patients requiring repeat surgery for graft revision, thrombectomy, or amputation (p < .05). Multivariate analysis indicated that the norepinephrine concentration at the time of emergence, but not type of anesthesia, correlated with reoperation for graft occlusion, suggesting that the previously reported beneficial effect of regional anesthesia may be due to modulation of the stress response. Myocardial infarction or cardiac death occurred in three patients. These patients had markedly increased catecholamine concentrations. CONCLUSIONS: The catecholamine response to lower extremity vascular surgery contributes to the development of postoperative hypertension and may also be important in the development of thrombotic complications.

Adult↗
PubMed1994

Atypical beta-adrenoceptor in bovine adrenal medulla.

Bovine adrenal medullary membranes were incubated with [125I]cyanopindolol to assess beta-adrenoceptor binding. Binding was saturable and specific; a single low affinity site (Kd = 750 pM) was identified. [125I]Cyanopindolol binding was displaced by micromolar concentrations of classic beta-adrenoceptor antagonists and by sodium-4-[-2-[2-hydroxy-2-(-3-chloro-phenyl) ethylamino] propyl] phenoxyacetate. These data are similar to reported binding of beta 3-adrenoceptors and may explain beta-adrenoceptor agonist modulation of chromaffin cell degranulation in this catecholamine rich environment.

Adrenal Medulla↗