Lorazepam and midazolam in the intensive care unit: a randomized, prospective, multicenter study of hemodynamics, oxygen transport, efficacy, and cost.

OBJECTIVES: To evaluate and compare the clinical efficacy, impact on hemodynamic and oxygen transport variables, safety profiles, and cost efficiency of sedation and anxiolysis with lorazepam vs. continuous infusion of midazolam in critically ill, intensive care unit patients. DESIGN: Multicenter, prospective, randomized, open-label study. SETTING: Teaching hospitals. PATIENTS: Ninety-five critically ill, mechanically ventilated patients with fiberoptic pulmonary artery catheters in place were randomly assigned to receive short-term (8 hrs) sedation with either intermittent intravenous injection lorazepam (group A, n = 50) or continuous intravenous infusion midazolam (group B, n = 45) titrated to clinical response. MEASUREMENTS AND MAIN RESULTS: The severity of illness, demographic characteristics, levels of anxiety and agitation, hemodynamic parameters, oxygen transport variables, quality of sedation, nursing acceptance, and laboratory chemistries reflecting drug safety were recorded. There were no significant differences with regard to demographic data, hemodynamic and oxygen transport variables, or levels of anxiety/agitation between the two groups at baseline, 5 mins, 30 mins, and 4 and 8 hrs after administration of sedation. There were no significant differences in the quality of sedation or anxiolysis. Midazolam-treated patients used significantly larger amounts of drug for similar levels of sedation and anxiolysis (14.4 +/- 1.2 mg/8 hrs vs. 1.6 +/- 0.1 mg/8 hrs, p = .001). Both drugs were safely administered and patient and nurse satisfaction was similar. CONCLUSIONS: Sedation and anxiolysis with lorazepam and midazolam in critically ill patients is safe and clinically effective. Hemodynamic and oxygen transport variables are similarly affected by both drugs. The dose of midazolam required for sedation is much larger than the dose of lorazepam required for sedation, and midazolam is therefore less cost-efficient.

Comparison of antegrade with antegrade/retrograde cold blood cardioplegia for myocardial revascularization.

There has been increasing interest in the use of retrograde coronary sinus perfusion for delivery of cardioplegic solution during myocardial revascularization. Despite evidence of improved cardiac protection, it is unclear if a combined antegrade/retrograde approach to myocardial preservation offers significant clinical benefits. One hundred twenty patients undergoing elective 1st-time coronary bypass surgery for 3-or-more-vessel disease received aortic root, antegrade cold blood cardioplegia (Group I, n=52) or combined antegrade/retrograde cardioplegia via coronary sinus cannulation (Group II, n=68). All preoperative variables were similar, including age, severity of coronary artery disease, functional status, and ejection fraction. Intraoperative and postoperative variables, including the degree of hypothermia, temperature of infusion solution, number of bypass grafts, defibrillation attempts and spontaneous return to sinus rhythm, the use of intraaortic balloon pump counterpulsation, and inotropic support during weaning from cardiopulmonary bypass, were not statistically different. Cardioplegia infusion time was longer in Group II than in Group I (2.5 +/- 0.8 vs 1.7 +/- 0.7 min, p < 0.05). The postoperative cardia output, electrocardiographic and cardiac enzyme evidence of ischemia, the need for temporary pacing, and 30-day morbidity were similar for both groups. The data indicate that in this non-risk-stratified group of patients, the route of cardioplegia administration is not a determinant of clinical outcome.

A pilot study of the effects of a perflubron emulsion, AF 0104, on mixed venous oxygen tension in anesthetized surgical patients.

A pilot study of a perfluorochemical (PFC) emulsion was undertaken to determine whether administration of a perflubron emulsion could result in measurable changes in mixed venous oxygen tension. Seven adult surgical patients received a 0.9-g PFC/kg intravenous dose of perflubron emulsion after acute normovolemic hemodilution (ANH). Hemodynamic and oxygen transport data were collected before and after ANH, immediately after PFC infusion, and at approximate 15-min intervals throughout the surgical period. There were no clinically significant hemodynamic changes associated with the administration of the PFC emulsion. There was a significant increase in mixed venous oxygen tension (PVO2) after the PFC infusion, while cardiac output and oxygen consumption were unchanged. As surgery progressed, the hemoglobin concentration decreased with ongoing blood loss while PVO2 values remained at or above predosing levels. Peak perflubron blood levels were 0.8 g/dL immediately postinfusion, and approximately 0.3 g/dL at 1 h. This pilot study demonstrates that administration of perflubron emulsion results in measurable changes in mixed venous oxygen tension during intraoperative ANH.

Descending thoracic aortomyoplasty: a technique for clinical application.

BACKGROUND: Descending thoracic aortomyoplasty is a form of skeletal muscle-powered cardiac assistance. Its use in clinical settings has been limited by the ligation of intercostal arteries necessary to complete a circumferential wrap of the aorta with the latissimus dorsi. METHODS: This study assessed the feasibility and the efficacy of aortomyoplasty constructed with a modified latissimus dorsi. A pericardial patch was attached to the latissimus dorsi and divided around the preserved intercostal arteries. Nine alpine goats (37 +/- 2 kg) underwent descending aortomyoplasty using this technique. All intercostal arteries were preserved. After a 6-week recovery period, the animals underwent a 6-week, incremental electrical conditioning program. After 90 postoperative days, animals were examined under anesthesia with the myostimulator on and off. RESULTS: Aortomyoplasty activation resulted in augmentation of mean diastolic aortic pressure by 16.0 +/- 0.9 mm Hg (23%). Significant improvements in cardiac index (40%), stroke volume index (37%), left ventricular stroke work index (49%), and mean arterial pressure (19%) were noted. An intravascular sonographic probe placed in the descending aorta revealed circumferential compression of the aorta during counterpulsation. Mean cross-sectional aortic area was reduced by 51.8%, from 210.1 +/- 7.1 to 108.9 +/- 6.7 mm2 during aortomyoplasty activation (p < 0.05). Histologic analysis confirmed the long-term patency of intercostal arteries. CONCLUSIONS: Descending aortomyoplasty, modified with an interposing patch of pericardium, effectively transfers skeletal muscle force across the aortic wall and assists cardiac function. This technique allows preservation of all aortic branches, and with this novel approach, the clinical utility of aortomyoplasty can now be explored.

Predictors of stroke after cardiac surgery.

From January 1, 1988 to September 30, 1993, 44 of 2,455 patients undergoing cardiac surgery for acquired heart disease at our institution sustained an intraoperative or postoperative cerebrovascular accident (CVA). Demographic data, atherosclerosis risk factors, past medical history, cardiac catheterization reports, and intraoperative findings were retrospectively reviewed. The highest rate of CVA was in the sub-group of patients undergoing simultaneous myocardial revascularization and carotid endarterectomy (18.2%). The lowest rate was in a group of patients who underwent aortic valve replacement (0.9%). Severe aortic arch atherosclerosis with the presence of atheromatous material or calcinosis at the cannulation site was identified intraoperatively in 43.2% of patients with neurological complications and in 5% of the group without CVA (x2 = 18.1, p = 0.0001). Of 44 patients with CVA, 13.6% had a history of preoperative completed stroke. CPB time was 90.1 +/- 4.9 min vs. 71.6 +/- 3.7 min (p = 0.004), and aortic cross-clamping time was 54.5 +/- 3.2 min compared to 39.8 +/- 2.7 min (p = 0.001) in groups with and without postoperative stroke, respectively. Hypertension was an independent risk factor of postoperative CVA (x2 = 9.5, p = 0.02), but age was not. Neurological complications correlated with high operative mortality (38.6%) and prolonged postoperative hospital stays (35.1 +/- 5.3). These data describe predictors for the development of post-cardiopulmonary bypass CVA and identify a high-risk subgroup for neurological events. The preoperative recognition of risk factors is an essential step toward the reduction of morbidity and mortality.

Latissimus dorsi and serratus anterior dynamic descending aortomyoplasty for ischemic cardiac failure.

Dynamic descending aortomyoplasty for cardiac assistance is a form of extraaortic, skeletal muscle-driven counterpulsation. Controversy exists regarding its clinical applicability and the most suitable muscle autograft for the procedure. Specifically, the ligation of intercostal vessels required for descending aortomyoplasty may not be tolerated clinically. This study compared the hemodynamic profiles and long-term function of latissimus dorsi (LD) aortomyoplasty to a split serratus anterior (SA) descending aortomyoplasty in which all intercostal vessels were preserved. Descending aortomyoplasty was performed in 11 goats. In 5, the SA was harvested and its distal end divided, facilitating a wrap of the aorta without ligation of intercostal arteries. In 6, the LD was used as a circumferential aortic wrap. At 90 days, an occluder placed on the left anterior descending artery created an ischemic event. Hemodynamic studies with and without assistance were performed in the ischemic and nonischemic states. Latissimus dorsi aortomyoplasty improved cardiac output 24% and 5.6%, stroke volume 29% and 66%, left ventricular stroke work index 30% and 166%, and coronary flow 4% and 3% in the normal and ischemic heart, respectively. Serratus anterior aortomyoplasty improved cardiac output 36% and 10%, stroke volume 42.8% and 13.5%, left ventricular stroke work index 64% and 21%, and coronary flow 8% and 4.3%, in the normal and ischemic heart, respectively. Two of the SA autografts were fibrotic and nonfunctional at 3 months. Aortomyoplasty with either SA or LD muscle improves cardiac function in the normal and ischemic heart. However, divided SA is associated with a higher rate of fibrosis and may be less suitable for the procedure.

Perfluorocarbons as blood substitutes: the early years. Experience with Fluosol DA-20% in the 1980s.

Clinical testing of perfluorocarbons (PFC) as blood substitutes began in the early 1980's in the form of Fluosol DA-20% (FDA), a mixture of perfluorodecalin and perfluorotripropylamine emulsified with Pluronic F68. We have treated 55 patients (Treatment (T) = 40; Control (C) = 15) with intravenous infusions of 30 cc/kg of FDA as part of either a randomized, clinical trial or a humanitarian protocol. All patients were Jehovah's Witnesses who refused blood transfusion and were severely anemic (mean hemoglobin = 4.6 g/d). FDA successfully increased dissolved or plasma oxygen content (P1O2 in ml/dl), but not overall oxygen content (T group: P1O2 baseline = 1.01 +/- .27, P1O2 12hrs = 1.58 +/- .47 [p = < .0001, t-test]; P1O2 12 hrs: T = 1.58 +/- .47, C = 1.00 +/- .31, p = < .0002, t-test). This effect persisted for only 12 hours post infusion, and had no apparent effect on survival. FDA is an ineffective blood substitute because of low concentration and short half-life. Improved emulsion design may resolve these problems, thereby producing a more effective agent. Our discussion will include a review of our data plus a summary of other reports of FDA efficacy as a blood substitute.

Improvement in circulatory and oxygenation status by perflubron emulsion (Oxygent HT) in a canine model of surgical hemodilution.

To examine the effect of a low dose of Oxygent HT on hemodynamics and oxygen transport variables in a canine model of profound surgical hemodilution, two groups of adult anesthetized splenectomized beagles were hemodiluted with Ringer's solution to Hb 7 g/dL. The treated group received 1 mL/kg Oxygent HT (90% w/v perflubron emulsion [perfluorooctyl bromide], Alliance Pharmaceutical Corp.) and both groups (7 controls and 10 treated) were further hemodiluted using 6% hydroxyethyl starch until cardiorespiratory decompensation occurred. Pulmonary artery catheterization data and oxygen transport variables were recorded at Hb decrements of 1 g/dL breathing room air. There was no difference among groups during initial hemodilution. However, in the Oxygent HT group there was a statistically significant improvement in mean arterial pressure, CVP, cardiac output, PvO2, SvO2, DO2, and pulmonary venous admixture shunt during profound hemodilution to Hb levels of 6, 5, and 4 g/dL. A low dose of Oxygent HT offered benefit in improving hemodynamics and oxygen transport parameters even under air breathing conditions in a model of surgical hemodilution. This effect was most apparent at lower levels of Hb.

Simultaneous coronary artery bypass and carotid endarterectomy. Determinants of outcome.

From January of 1988 to May of 1993, simultaneous single-stage coronary revascularization and carotid endarterectomy was performed in 33 patients (mean age, 69 years). Thirty-one patients (94%) were in New York Heart Association class III or IV, 15 (46%) had unstable angina, and 7 (21%) were operated on because of evolving myocardial infarction. One or more previous myocardial infarctions were present in 18 patients (54%). Nineteen patients (58%) presented with neurologic symptoms, and 22 (67%) had severe bilateral carotid stenosis. Thirty (91%) had triple-vessel or left main coronary artery disease. Sequential reconstruction of the carotid artery followed by coronary artery bypass grafting was performed in all patients. In 4 cases, additional cardiac procedures were performed. Operative mortality (6%) was cardiac related. Perioperative morbidity included myocardial infarction in 1 patient (3%) and neurologic deficit in 6 (18%), with permanent functional impairment in 2 patients (6%). The stroke rate was higher in the bilateral than in the unilateral carotid stenosis group (22.7% vs 9.1%, p = 0.047). Previously completed stroke influenced the operative outcome (55.6% vs 4.2%, p = 0.003). Low ejection fraction (33.5% +/- 7.5% vs 52.8% +/- 3.5%, p = 0.03) and left main coronary artery disease (36% vs 5%, p = 0.03) also predicted postoperative neurologic complications. During a mean follow-up of 24.6 +/- 3.5 months, 3 patients died. The 5-year life-table survival rate was 85%. Eighty-nine percent of long-term survivors were free of cardiovascular disease symptoms. Our results show that the out come of simultaneous carotid endarterectomy/coronary artery bypass grafting in this high-risk population depends upon the preoperative absence or presence of completed stroke or bilateral carotid stenosis, upon the preoperative ejection fraction, and upon the extent of the left main coronary artery disease.

Transfusion and surgery.

In this survey of transfusion in surgery, we have attempted to provide the surgeon with an understanding of the problems associated with homologous transfusion and a practical knowledge of treatment strategies and alternatives designed to reduce homologous blood exposure. Such a review cannot be encyclopedic. Our hope is that it will serve the reader as a stimulus to examine his or her transfusion practices and as a guide for future self-learning.

Effect of sodium nitroprusside on paraplegia during cross-clamping of the thoracic aorta.

Sodium nitroprusside (SNP) is usually used to control excessive proximal pressure after aortic cross-clamping. To assess the effect of SNP on circulatory dynamics, somatosensory evoked potentials, and neurologic outcome, 10 adult mongrel dogs that underwent 45 minutes of cross-clamping of the thoracic aorta were randomly assigned to receive either 50 mg/kg of SNP or no treatment for excessive proximal hypertension. There was a statistically significant difference noted between the SNP-treated animals and the control animals in terms of the proximal mean arterial pressures (112 +/- 13 versus 142.2 +/- 15 mm Hg, respectively; p < 0.05) and the mean distal arterial pressures (15 +/- 3 mm Hg versus 23 +/- 1 mm Hg; p = 0.04). However, the electrical activity of the spinal cord, as indicated by the somatosensory evoked potentials, returned significantly faster in the nontreated group than in the SNP-treated group (15 +/- 9 versus 44 +/- 13 minutes; p < 0.05). Control animals exhibited a significantly better neurologic outcome and no paraplegia 24 hours postoperatively. We conclude that the use of SNP to treat excessive proximal hypertension may be detrimental to the spinal cord during cross-clamping of the thoracic aorta, resulting in a decline in the ischemic tolerance.

A surgical approach to chronic aortomyoplasty in the goat model.

The left latissimus dorsi skeletal muscle of seven male goats was prepared and applied circumferentially to the descending aorta just below the subclavian artery. Stimulation of the neural pedicle of the latissimus dorsi was performed in an attempt to convert it to a fatigue-resistant cardiac-like muscle. Timing of the stimulus was in diastole. Biochemical assays established the conversion, and echocardiography demonstrated aortic compressions in the area of the muscle wrap. Although limited in numbers, the converted latissimus dorsi muscle in the extra-aortic position appears to provide diastolic augmentation.

Implantation of a cardioverter-defibrillator after coronary artery bypass surgery.

The implantable cardioverter-defibrillator (ICD) has been used in conjunction with surgical coronary revascularization for prevention of postoperative malignant arrhythmias. However, there is no consensus regarding which patient should receive concomitant insertion of the ICD system in a one stage (patches and generator) or two stage (patches, and subsequent implantation of the generator) procedure. To assess differences in hospital course and outcome, the authors studied 8 survivors of sudden death syndrome and 17 patients with preoperative ventricular tachycardia refractory to conventional antiarrhythmic therapy who underwent coronary revascularization and prophylactic implantation of an ICD system in either one or two stages. Patients with advanced coronary disease, poor ventricular function, and silent ischemia received the ICD system in one stage. Those with good ventricular function and well defined coronary pathology received only patches concomitant with myocardial revascularization. Seventy-nine percent of the patients with patches needed subsequent implantation of the ICD generator, as determined by postoperative electrophysiologic studies. There were three postoperative deaths unrelated to arrhythmias. There was no difference between the groups regarding the number of ICD discharges. It was concluded that the prophylactic use of the ICD system is an important adjuvant in the treatment of postoperative malignant arrhythmias for patients undergoing myocardial revascularization. The insertion of the ICD, however, should be based on pathophysiologic considerations and postoperative electrophysiologic findings. This may result in important savings in terms of unnecessary cost and operative procedures.

Determinants of outcome in lesions of the thoracic aorta in patients with multiorgan system trauma.

Of all patients presenting at our level 1 trauma center with multiorgan system injuries, 33 have been identified with acute lesions of the thoracic aorta. Mean severity injury score was 24 +/- 3. Four patients underwent resuscitative thoracotomy upon arrival in the emergency department. One survived and fully recovered. The rest underwent diagnostic procedures and repair of aortic lesions in conjunction with surgical treatment of other injured organ systems. The overall survival rate was 82 percent. Survivors arrived significantly faster to the ED and had lesser degree of multiorgan system injuries. There was no difference in the time spent to make the diagnosis of acute aortic disruption for survivors and nonsurvivors, nor was a difference in time to arrive in the operating room once the diagnosis of aortic injury has been established. Morbidity was related to ischemia to distal organs in four patients of whom two presented with multiple lesions of the thoracic aorta; two remained paralyzed and two had only lower limb spasticity. All discharged survivors were alive at 12 months' follow-up. The type of surgical repair did not influence the outcome of patients with single, typical aortic lesions; however, "clamp/sew" technique was not adequate when multiple aortic tears were found intraoperatively. The outcome of surgical treatment of the traumatic aortic lesions of patients with polytrauma may be influenced by the speed of arrival to the ED, the magnitude of multiorgan system involvement, and the application of appropriate surgical technique for repair according to the intrathoracic findings and the timing of aortic repair vis-a-vis other surgical treatment.

Continuous venous oximetry for hemodynamic and oxygen transport stability post cardiac surgery.

Under the diagnostic-related group (DRG) reimbursement system, hospitals are looking to decrease costs related to unnecessary laboratory measurements. To assess the efficacy of continuous SvO2 as the only means to monitor the balance of the oxygen transport of the stable postoperative cardiac patient in the ICU, we studied 26 adult patients undergoing cardiac surgery with an uneventful postoperative course. All subjects had an Opticath fiberoptic PA catheter inserted for 29.6. +/- 11.0 hours (range 16-66) and spent an average of 42.4 +/- 17.5 hours in the Intensive Care Unit (range 20-87). Cardiac output, and Hemoglobin/Hematocrit were determined serially every 2 hours during the first 6 postoperative hours and 4 hours respectively according to our ICU practice. Arterial blood gases were determined freely in relation to changes in the hemodynamic and respiratory status. No clinical decisions were undertaken on the basis of SvO2. Retrospectively it was determined whether basing decisions on the SvO2 would have reduced the number of unnecessary cardiac outputs, ABGs and Hgb/Hcts. Using the SvO2 as potential indicator of hemodynamic and oxygen transport stability it could significantly reduce the number of determinations per patient, ie, cardiac output (11.7 +/- 4.2 vs 2.1 +/- 0.3, p less than 0.05), ABGs (11.3 +/- 2.8 vs 2.8 +/- 0.4, p less than 0.05) and Hgb/Hcts (5.7 +/- 1.3 vs 2.0 +/- 0.0, p less than 0.05). The use of SvO2 would save the hospital $84.5 +/- 27.5 (range 31.5 +/- 140.9) per stable patient in the ICU and a total of 220.4 +/- 69.9 minutes (range 90-300) of ICU nursing time.(ABSTRACT TRUNCATED AT 250 WORDS)

Routine initial computed tomography of the chest in blunt torso trauma.

Computer tomography (CT) is an effective technique in the initial evaluation of the abdomen and head following blunt trauma. To evaluate the role of CT of the thorax, a prospective study comparing routine early thoracic CT scanning with initial chest roentgenogram (CXR) was carried out on 73 patients with blunt torso trauma undergoing concomitant abdominal CT examination. Initial CXR and CT scans were interpreted independently by radiologists in a blinded fashion. CXR diagnosed more bony injuries than CT, while the CT identified pulmonary contusions and effusions more accurately. Only those contusions diagnosed by CXR proved clinically significant. Patient treatment was changed in one case based on CT findings. In the absence of CXR findings, chest CT scanning frequently identifies abnormalities with limited clinical significance. Although more sensitive, CT of the thorax has a limited role in the initial emergent evaluation of victims of blunt torso trauma.

Ventricular free-wall rupture after myocardial infarction. Treatment and outcome.

Ventricular free-wall rupture remains one of the leading causes of death after myocardial infarction (MI). With increased abilities for diagnosis and resuscitation techniques, surgical correction of free-wall myocardial defects resulting from ischemia and necrosis may become a simple modality of treatment, resulting in improvement of the survival rate. We are reporting our experience with four patients with ventricular free-wall rupture after MI, with emphasis on clinical presentation, diagnosis, and surgical management.

Silicone pouch for protection of automatic implantable cardioverter-defibrillator leads.

Automatic implantable cardioverter-defibrillator has become routine treatment for recurrent, drug-resistant ventricular tachycardia. Although there is documentation regarding clinical experience and device performance, there is little information on how to avoid complications related to the retrieval of sensing and defibrillation leads from the subcutaneous space. We are reporting our experience with a silicone pouch for protection of automatic implantable cardioverter-defibrillator leads that allows immediate and simple retrieval of the leads in case an automatic implantable cardioverter-defibrillator generator is needed.

Arterial-venous perfusion without anticoagulation: the impeller centrifugal pump.

A study was designed to test the effects of the absence of anticoagulation in the extracorporeal circuit. Five swine were subjected to this experiment utilizing the impeller centrifugal pump during which neither heparin nor any other anticoagulant was used. The extracorporeal circuit consisted of polyvinylchloride tubing, a Centri-Med pump and an external stainless steel heat exchanger that was primed with albuminized Ringer's solution. An arterial-venous circuit was employed with oxygenation supplied from the subject's lungs. A series of blood aliquots were analyzed for coagulation at various times throughout the procedure. Following total body cooling using topically applied ice water, the subjects were rewarmed utilizing bypass. Within 10 minutes after the initiation of bypass, the circuits became clotted, rendering perfusion and subsequent warming ineffective. The lab values indicated that intrinsically activated coagulation occurred upon exposure to the extracorporeal apparatus. Flow visualization studies revealed a source of stagnant blood flow in the area around the hub of the pump head. Blood clot was similarly located in this area, with clot extension throughout the return circuit being realized. It is imperative that areas of stagnation be eliminated from extracorporeal circuits, since they may be potential sites for clot formation.