Ultrarapid opioid detoxification: effects on cardiopulmonary physiology, stress hormones and clinical outcomes.

This study explored the acute and long-term consequences of ultrarapid opioid detoxification (URD) in individuals with opioid dependence. In an open case series, seven patients underwent URD and subsequent treatment with daily naltrexone. Structured interviews, integrated rehabilitation and hair sampling were employed in the 12-week course of longitudinal follow-up. Cardiac and pulmonary physiology did not change significantly during the anesthesia phase of URD, but plasma ACTH and cortisol levels increased 15- and 13-fold, respectively. Marked withdrawal and tachypnea in all patients and respiratory distress in one patient occurred during the acute post-anesthesia phase. Withdrawal scores were significantly elevated for 3 weeks compared with baseline in the face of minimal self-reported craving for opioids. Anxiety, depression and vegetative symptoms improved gradually. Four patients remained abstinent of opioid use, two reported a brief period of opioid intake and one relapsed into daily opioid consumption. Given its effect on breathing and stress hormones, this procedure should be conducted by experienced anesthesiologists. The fact that URD and subsequent naltrexone treatment appears to cause a dissociation effect in the usual relationship between withdrawal and craving has implications for behavioral pharmacology. Further research is needed on the efficacy, safety, mechanisms and neurobiological sequelae of the procedure.

Institutional variability in red blood cell conservation practices for coronary artery bypass graft surgery. Institutions of the MultiCenter Study of Perioperative Ischemia Research Group.

OBJECTIVE: To assess whether substantial institutional variability exists in red blood cell conservation practices associated with coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized patient enrollment and data collection. SETTING: Twenty-four U.S. academic institutions participating in the Multicenter Study of Perioperative Ischemia. PARTICIPANTS: A well-defined subset of primary CABG surgery patients (n = 713) expected to be at low risk for bleeding and exposure to allogeneic transfusion. INTERVENTIONS: None (observational study). MEASUREMENTS AND MAIN RESULTS: Frequency of use of red blood cell conservation techniques was determined among institutions. Correlation was determined between use of each technique and transfusion of allogeneic red blood cells and between use of each technique and median institutional blood loss. Significant variability (p < 0.01) was detected in institutional transfusion practice with respect to the use of predonated autologous whole blood, normovolemic hemodilution, red cell salvage, and reinfusion of shed mediastinal blood. The frequency of institutional use of these techniques was not associated with allogeneic transfusion (r2 < 0.15) or blood loss (r2 < 0.10) in the low-risk population of patients examined. CONCLUSIONS: Institutions vary significantly in perioperative blood conservation practices for CABG surgery. Further study to determine the appropriate use of these techniques is warranted.

Safety and efficacy of shed mediastinal blood transfusion after cardiac surgery: a multicenter observational study. Multicenter Study of Perioperative Ischemia Research Group.

OBJECTIVE: To examine the efficacy and safety of shed mediastinal blood (SMB) transfusion in preventing allogenic red blood cell (RBC) transfusion. DESIGN: An observational clinical study. SETTING: Twelve US academic medical centers. PARTICIPANTS: Six hundred seventeen patients undergoing elective primary coronary artery bypass grafting. INTERVENTIONS: Patients were administered SMB transfusion or not, according to institutional and individual practice, without random assignment. MEASUREMENTS AND RESULTS: The independent effect of SMB transfusion on postoperative RBC transfusion was examined by multivariable modeling. Potential complications of SMB transfusion, such as bleeding and infection, were examined. Three hundred twelve of the study patients (51%) received postoperative SMB transfusion (mean volume, 554 +/- 359 mL). Patients transfused with SMB had significantly lower volumes of RBC transfusion than those not receiving SMB (0.86 +/- 1.50 v 1.08 +/- 1.65 units; p < 0.05). However, multivariable analysis showed that SMB transfusion was not predictive of postoperative RBC transfusion. Demographic factors (older age, female sex), institution, and postoperative events (greater chest tube drainage, lower hemoglobin level on arrival to the intensive care unit, and use of inotropes) were significant predictors of RBC transfusion. The volume of chest tube drainage on the operative day (707 +/- 392 v 673 +/- 460 mL; p = 0.30), reoperation for hemorrhage (3.1% v2.5%; p = 0.68), and overall frequency of infection (5.8% v 6.6%; p = 0.81) were similar between patients receiving and not receiving SMB, respectively. However, in patients who did not receive allogenic RBC transfusion, there was a significantly greater frequency of wound infection in the SMB group (3.6% v0%; p = 0.02). CONCLUSION: These data suggest that SMB is ineffective as a blood conservation method and may be associated with a greater frequency of wound infection.

Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines: a 24-institution study. Institutions of the Multicenter Study of Perioperative Ischemia Research Group.

BACKGROUND: An estimated 20% of allogeneic blood transfusions in the United States are associated with cardiac surgery. National consensus guidelines for allogeneic transfusion associated with coronary artery bypass graft (CABG) surgery have existed since the mid- to late 1980s. The appropriateness and uniformity of institutional transfusion practice was questioned in 1991. An assessment of current transfusion practice patterns was warranted. METHODS: The Multicenter Study of Perioperative Ischemia database consists of comprehensive information on the course of surgery in 2,417 randomly selected patients undergoing CABG surgery at 24 institutions. A subset of 713 patients expected to be at low risk for transfusion was examined. Allogeneic transfusion was evaluated across institutions. Institution as an independent risk factor for allogeneic transfusion was determined in a multivariable model. RESULTS: Significant variability in institutional transfusion practice was observed for allogeneic packed red blood cells (PRBCs) (27-92% of patients transfused) and hemostatic blood components (platelets, 0-36%; fresh frozen plasma, 0-36%; cryoprecipitate, 0-17% of patients transfused). For patients at institutions with liberal rather than conservative transfusion practice, the odds ratio for transfusion of PRBCs was 6.5 (95% confidence interval [CI], 3.8-10.8) and for hemostatic blood components it was 2 (95% CI, 1.2-3.4). Institution was an independent determinant of transfusion risk associated with CABG surgery. CONCLUSIONS: Institutions continue to vary significantly in their transfusion practices for CABG surgery. A more rational and conservative approach to transfusion practice at the institutional level is warranted.

Effect of recombinant human erythropoietin on transfusion risk in coronary bypass patients.

BACKGROUND: Patients having a cardiac operation frequently require allogeneic blood transfusions despite surgical blood-conservation techniques. Recombinant human erythropoietin (Epoetin alfa) may augment this conservation by stimulating erythropoiesis. The safety and efficacy of perioperative use of Epoetin alfa to reduce the need of allogeneic transfusion was studied. METHODS: A multicenter double-blind, placebo-controlled, parallel-group study involved 182 patients having coronary artery bypass grafting and randomized to receive Epoetin alfa (300 or 150 IU/kg) or placebo subcutaneously for 5 days before, on the day of, and for 2 days after operation. RESULTS: Perioperative Epoetin alfa resulted in greater increases in baseline to preoperative hemoglobin levels and hematocrit (300 IU/kg) and in presurgery to postsurgical day 1 reticulocyte counts versus placebo (p < or = 0.05). However, there was no significant difference in transfusion requirements. Incidences of adverse events were similar in all study groups. CONCLUSIONS: Lower incidences of allogeneic blood exposure were observed in both Epoetin alfa-treated groups; however, the differences between all treatment groups were not significant. This was probably due to the relatively short 5-day preoperative course of Epoetin alfa therapy. There were no significant differences between the three groups relative to safety. Epoetin alfa was well tolerated in this population.

Aprotinin in primary valve replacement and reconstruction: a multicenter, double-blind, placebo-controlled trial.

BACKGROUND: Patients having cardiac operations often require blood transfusions. Aprotinin reduces the need for blood transfusions during coronary artery bypass graft operations. To determine the safety and effectiveness of aprotinin in reducing the use of allogeneic blood and postoperative mediastinal chest tube drainage, we studied 212 patients undergoing primary sternotomy for valve replacement or repair. METHODS: This study was multicenter, randomized, prospective, double-blind, and placebo-controlled. Patients received high-dose aprotinin (n = 71), low-dose aprotinin (n = 70), or placebo (n = 71). The study medication was given as a loading dose followed by a continuous infusion and pump prime dose. Heparin administration was standardized. Transfusions, postoperative mediastinal shed blood, and adverse events were tracked. RESULTS: Demographic profiles were similar among the treatment groups. Aprotinin did not decrease the percentage of patients receiving transfusions when compared with placebo (high-dose aprotinin, 63%, p = 0.092; low-dose aprotinin, 52%, p = 0.592; placebo, 48%). Aprotinin was associated with a reduction in the volume of mediastinal shed blood (high-dose aprotinin vs placebo, p = 0.002; low-dose aprotinin vs placebo, p = 0.017). Adverse events were equally distributed among the treatment groups except for postoperative renal dysfunction (high-dose aprotinin, 11%; low-dose aprotinin, 7%; placebo, 0%; p = 0.01). A disproportionate number of patients in the high-dose aprotinin group with postoperative renal dysfunction also had diabetes mellitus. CONCLUSIONS: Aprotinin treatment in this population did not reduce allogeneic blood use, although there were significant reductions in the volume of mediastinal shed blood.

Alternatives to allogeneic blood use in surgery: acute normovolemic hemodilution and preoperative autologous donation.

Acute normovolemic hemodilution (ANH) is a common blood conservation strategy in elective surgical procedures. Moderate ANH is safe in patients > 60 years of age; ANH is not recommended for patients who have coronary artery disease, significant anemia, renal disease, severe hepatic disease, pulmonary emphysema, or obstructive lung disease. Preservation of oxygen delivery during ANH depends on the maintenance of normovolemia to avoid decompensation and falling cardiac output. Preoperative autologous donation (PAD) as a blood conservation strategy has the advantage of protecting the patient from risks associated with allogenic transfusion, but it is expensive and time consuming. No protocols have established a preference for either ANH or PAD; an early study suggested that ANH is less expensive and more effectively preserves blood components, but other researchers warn that the methodology for ANH remains unresolved.

Distal circulatory support for thoracic aortic operations: effects on intracranial pressure.

Spinal cord ischemia can result from aortic clamping during thoracic aortic operations. The perfusion gradient for spinal cord perfusion is positively influenced by distal aortic pressure and negatively influenced by intracranial pressure (ICP). Hemodynamic and ICP changes were examined in a swine model of descending thoracic aortic surgery where distal aortic perfusion was achieved under one of three conditions: (1) clamping without support, (2) a passive aortofemoral shunt, or (3) a left atrium-femoral artery bypass system. With aortic clamping alone, ICP increased from 9.8 +/- 2.2 mm Hg to 15.2 +/- 2.8 mm Hg (p < 0.05). With passive shunting, ICP was decreased to 13.8 +/- 3.0 mm Hg, which was still significantly elevated above baseline. However, with active bypass, ICP remained at control level (9.8 +/- 2.2 mm Hg). Mean distal aortic pressure, which was 82 +/- 10 mm Hg in the control state, decreased to 20 +/- 0.5 mm Hg with clamping alone and to 39 +/- 9 mm Hg with passive shunting, whereas with active support, a distal pressure of 64 +/- 8 mm Hg was achieved. In contrast to passive shunting, active distal bypass results in maintenance of ICP at baseline levels and results in distal aortic pressure significantly greater than that achieved with either aortic clamping alone or passive shunting. Thus, active distal circulatory support produces the greatest salutary effect on the two determinants of the spinal cord perfusion pressure gradient: ICP and distal aortic pressure. This support modality may be the best adjunctive technique to maintain the spinal cord perfusion gradient and hence minimize the risk of ischemic injury.

Recombinant platelet factor 4 reversal of heparin in human cardiopulmonary bypass blood.

The ability of recombinant platelet factor 4, a protein of human origin with high heparin affinity, and the present clinical heparin reversal agent, protamine, to neutralize heparin in human whole blood was studied by means of three standard whole blood coagulation tests: whole blood clotting time, heparin assay, and activated clotting time. Ten subjects were chosen at random among patients undergoing cardiopulmonary bypass operations. Heparinized blood, free of protamine, was obtained from the bypass reservoir for testing. Whole blood aliquots, without reversal agents (controls) or with either protamine (10, 20, 30, or 40 micrograms/ml) or recombinant platelet factor 4 (10, 20, 40, or 80 micrograms/ml), were analyzed. The quantity of each agent required to reverse the ten samples, using 95% upper confidence bounds (t distribution) was determined for each method. Recombinant platelet factor 4 reversed heparin at 40 micrograms/ml and protamine at 20 micrograms/ml, suggesting a reversal ratio for recombinant platelet factor 4/protamine of 2:1 on a milligram basis. Further, currently available methods for testing coagulation should be reliable, without modification, to monitor the restoration of normal coagulation parameters with recombinant platelet factor 4 after cardiopulmonary bypass.

Indications for the use of pacing pulmonary artery catheters in cardiac surgery.

Several varieties of pulmonary artery catheters (PACs) with pacing capabilities are now available. Although specific recommendations for prophylactic perioperative placement of pacemakers have been offered previously, the authors believe that those recommendations warrant further examination, taking into consideration the availability of new pacing modalities. Toward this end, the use of pacing PACs in cardiac surgical patients was prospectively examined. In 600 consecutive adult patients with PACs placed prior to cardiopulmonary bypass (CPB), the cardiac anesthesiologist recorded if a pacing PAC was placed, the indications for placing it, and whether the catheter was used to pace. If a pacing PAC was not chosen, the anesthesiologist indicated whether cardiac pacing was needed prior to CPB. In all patients, the presence and specifics of the following five possible indications were documented: sinus node dysfunction/bradydysrhythmias, atrioventricular heart block, fascicular or bundle branch block, cardiac reoperation, and/or valvular heart disease. PACs with pacing capability were placed in 180 of the 600 patients (30.0%) and were used in 34 of these 180 patients (18.8%). In 4 of 420 patients (0.95%) without pacing PACs, cardiac pacing was needed prior to CPB. The following preoperative diagnoses were significant predictors (P less than .05) for the use or need for pacing catheters: sinus node dysfunction/bradydysrhythmias, a history of transient complete atrioventricular block, aortic stenosis, aortic insufficiency, and reoperation. The majority of adult patients undergoing cardiac surgery do not require the use of a pacing PAC prior to CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Left atrial V waves following mitral valve replacement are not specific for significant mitral regurgitation.

Left atrial or pulmonary capillary wedge pressure V waves are used immediately after mitral valve replacement to evaluate valve competence. However, their correlation with hemodynamically significant regurgitation has not been established. Transesophageal echocardiography (TEE) was used to prospectively examine whether left atrial V waves represented significant mitral regurgitation in 11 patients undergoing mitral valve replacement. Left atrial pressure V waves were measured in the immediate postcardiopulmonary bypass period by direct cannulation of the right superior pulmonary vein and recorded on a paper chart recorder. In each patient, three evaluations of mitral regurgitation by Doppler TEE were made at 15-minute intervals. In 22 of 33 evaluations, left atrial V waves with peak V wave height more than 5 mm Hg above the mean left atrial pressure were present. However, only in 3 of these periods did transesophageal echocardiography show evidence of more than trace mitral regurgitation by pulsed Doppler and color flow mapping. As indicators of mild-to-severe mitral regurgitation diagnosed by TEE, left atrial V waves had a specificity for the three evaluation periods of 40%, 30%, and 40%. Left atrial V waves with peak height greater than 5 mm Hg above mean left atrial pressure frequently appear following mitral valve replacement, but these V waves are nonspecific signs of mitral regurgitation.

Effects of prolonged transesophageal echocardiographic imaging and probe manipulation on the esophagus--an echocardiographic-pathologic study.

Transesophageal echocardiography is being increasingly utilized in the operating room and intensive care and ambulatory settings. However, to date no data are available concerning possible trauma of the transesophageal echocardiographic technique to the esophagus due to probe insertion, manipulation or direct ultrasound energy transmission. To test the hypothesis that transesophageal manipulations caused no traumatic or thermal injury to the esophageal mucosa, 12 animals were studied with continuous transesophageal echocardiography for a period of variable duration (mean 4.6 h +/- 51 min). The study group consisted of four monkeys (mean weight 5.7 +/- 0.6 kg and eight mongrel dogs (mean weight 29.8 +/- 1.4 kg). The eight dogs were studied during right heart bypass with full heparinization for 6.6 +/- 0.2 h, whereas the four monkeys were studied for 60 to 90 min in the absence of cardiopulmonary bypass and anticoagulation. Immediately after completion of transesophageal echocardiography in each case, the esophagus was entirely excised. Detailed macroscopic and microscopic examination of the esophagus revealed no significant mucosal or thermal injury. This preliminary animal study suggests that transesophageal echocardiography is safe for the esophageal mucosa in animals as small as 5 kg in weight, despite prolonged use and in the presence of systemic anticoagulation.

An engineering critical incident: direct current burn from a neuromuscular stimulator.

A patient received a third-degree, direct current (DC) burn on the wrist from a neuromuscular stimulator (NMS) that had been modified by a biomedical technician. The event is used to illustrate the accident process, procedures in investigation of engineering-related incidents, and the mechanisms of burns caused by DC. Similar to most industrial accidents, this one had several contributing causes. It demonstrates the need for thorough review and testing of device modifications, the subtle effects of personnel shortages, the dangers of grounded electrosurgical units, and the ways in which seemingly minor features of a device can contribute indirectly to an injury. Accident investigations should be instituted immediately following an event, but care must be taken to ensure that vital information is neither lost nor altered.

Fentanyl and sufentanil anesthesia revisited: how much is enough?

This study was undertaken to determine if fentanyl and sufentanil could produce dose-related suppression of hemodynamic and hormonal responses to surgical stimulation. Eighty patients scheduled for elective CABG were studied in two consecutive protocols: protocol I was a randomized double-blind study of 40 patients who received a single dose of fentanyl (50 or 100 micrograms/kg) or sufentanil (10, 20, or 30 micrograms/kg). Hemodynamic measurements and hormonal concentrations (renin, aldosterone, cortisol, and catecholamines) were determined before and after induction and after intubation and sternotomy. Protocol II was an open randomized study of 40 patients who received sufentanil in one of four doses: 30 micrograms/kg as a single dose, 10 micrograms/kg plus infusion 0.05 microgram.kg-1.min-1, 20 micrograms/kg plus infusion 0.1 microgram.kg-1.min-1, or 40 micrograms/kg plus infusion 0.2 microgram.kg-1.min-1. Hemodynamic measurements and plasma sufentanil and catecholamine concentrations were determined before and after induction and after intubation, sternotomy, and aortic cannulation. Both protocols defined a hemodynamic response as a 15% or more increase in systolic blood pressure (SBP) from control and a hormonal response 50% or more increase over control. During protocol I, 18 patients had a hemodynamic response (average increase in SBP 22.6 +/- 2%) and 35 patients had a total of 59 hormonal responses. During protocol II, 24 patients had a hemodynamic response (average increase in SBP - 31 +/- 3%) and there were 15 catecholamine responses. There were no differences between dose groups in either protocol. It was concluded that in these dose ranges, suppression of hemodynamic or hormonal stress responses is not related to opioid dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Con: colloids should not be added to the pump prime.

It is concluded that there is good scientific basis for an approach that avoids colloid priming solutions as routine for all adult CPB patients. There may be selected individuals who might benefit from colloid therapy; for instance, patients who are predicted to require high left atrial pressures postbypass, those who are borderline for getting through their surgical experience without a homologous red cell transfusion, and patients coming for surgery with a clinically important lung water elevation. In this time of cost constraints there are many more scientifically worthy therapies that could be made available to patients. We should focus on these and resist "luxury items" like routine colloid CPB priming solutions.