Time to peak effect of neostigmine at antagonism of atracurium- or vecuronium-induced neuromuscular block

Study Objective: (1) To determine the time to peak effect of neostigmine (time to peak antagonism) during atracurium- or vecuronium-induced neuromuscular block; and (2) to determine the effect on time to peak effect of neostigmine during atracurium-induced neuromuscular block, when the dose of neostigmine is increased from 35 μg/kg to 70 μg/kg.

Design: Prospective, randomized clinical study.

Setting: Gynecologic operating room suite at a university hospital.

Patients: 45 ASA I and II women admitted for gynecologic laparotomy.

Interventions: Anesthesia was performed with thiopental sodium, fentanyl, halothane, nitrous oxide, and atracurium or vecuronium. Train-of-four (TOF) stimulation and mechanomyography were used to monitor neuromuscular transmission. Neostigmine was administered while a constant degree of neuromuscular block was maintained at a twitch height at a point between 4% and 11% of the control twitch height, using a continuous infusion of atracurium or vecuronium. The patients were randomized to three groups, with 15 patients in each group. Group 1 received atracurium block antagonized with neostigmine 35 μg/kg; group 2 received vecuronium block antagonized with neostigmine 35 μg/kg; and group 3 received atracurium block antagonized with neostigmine 70 μg/kg.

Measurements and Main Results: The degree of neuromuscular block at antagonism was similar in the three groups. Time to peak effect (mean ± SD) on TOF ratio was significantly longer in Group 1 (9.7 ± 3.0 minutes) versus Group 2 (6.6 ± 1.4 minutes; (p < 0.05). The time to peak effect on TOF ratio during atracurium-induced block was reduced from 9.7 ± 3.0 minutes to 6.3 ± 2.0 minutes when the dose of neostigmine was increased from 35 μg/kg to 70 μg/kg (p < 0.05). The peak effect on TOF ratio was significantly greater in Group 3 compared with Group 1 (p < 0.05), while it was similar in groups 1 and 2.

Conclusion: The time to peak effect of neostigmine 35 μg/kg is about 6 to 10 minutes when antagonizing a constant degree of atracurium- or vecuronium-induced neuromuscular block at a twitch height at a point between 4% and 11%. Even though the time to peak effect was longer with atracurium than with vecuronium, clinically significant differences between the antagonizing effect of atracurium versus vecuronium block were not demonstrated. The time to peak effect during atracurium-induced block decreased when the dose of neostigmine was increased from 35 μg/kg to 70 μg/kg.     

Pharmacodynamic effects of three doses of ORG 9426 used for endotracheal intubation in humans

Study Objective: To determine the pharmacodynamic characteristics of three incremental doses of ORG 9426 used for endotracheal intubation in patients.

Design: Double-blind, randomized administration of one of three doses of intravenous ORG 9426.

Setting: Inpatients requiring surgery at Georgetown University Medical Center.

Patients: Thirty-six patients, ages 18 to 65, ASA physical status I, II, and III, scheduled for general surgery.

Interventions: After Georgetown University Institutional Review Board approval and patient consent, patients were premeditated with midazolam or droperidol. Anesthesia was induced with thiopental sodium and fentanyl. Anesthesia was maintained with 60% nitrous oxide in oxygen. The ulnar nerve was stimulated supramaximally with a 2 Hz train-of four (TOF) every 20 seconds. Thumb contractions were measured with a force transducer. When TOF and anesthesia were stable, 2, 2.5, or 3 times the ED₉₅ of ORG 9426 (570 μg/kg 710 μg/kg or 850 μg/kg) was administered randomly. Tracheal intubation was attempted at maximal depression of the first TOF response (T₁).

Measurements and Main Results: The following parameters were measured: time interval from the injection of ORG 9426 to 90% depression of T₁ (T₁ 90% block), maximal T₁ depression (onset time), intubating conditions, clinical duration (time for return of T₁ to 25% of control), heart rate (HR), blood pressure (BP), and any adverse clinical experience. ORG 9426 provided adequate intubating conditions in all patients but two, independent of the dose used. Its onset time was rapid, but increasing the dose did not shorten the onset. T₁ 90% block was achieved rapidly (75 ± 25 seconds to 78 ± 18 seconds, means ± SD). The clinical duration of ORG 9426 was relatively short and lengthened with increasing doses (from 36 ± 18 minutes at 570 μg/kg to 42 ±10 minutes at 850 μg/kg. Spontaneous twitch recovery from 10% to 25% was similar in all dosage groups (5 ± 1 minutes to 6 ± 4 minutes). No clinically significant changes in HR and BP and no adverse clinical experiences were noted in any group.

Conclusion: These findings warrant further clinical evaluation of ORG 9426 for induction and maintenance of muscle relaxation in humans.     

Patient-controlled drug administration during local anesthesia: A comparison of midazolam, propofol, and alfentanil

Study Objective: To evaluate the perioperative effects of alfentanil, midazolam, and propofol when administered using a patient-controlled analgesia (PCA) device during local anesthesia.

Design: Randomized, single-blind comparative study.

Setting: Outpatient surgery center at a university teaching hospital.

Patients: Ninety outpatients undergoing minor elective surgical procedures with local anesthetic infiltration were assigned to one of three treatment groups.

Interventions: After premedication with midazolam 1 mg intravenously (IV) and fentanyl 50 μg IV, patients were allowed to self-administer 2 ml bolus doses of either alfentanil 250 μg/ml, midazolam 0.4 mg/ml, or propofol 10 mg/ml at minimal intervals of 3 minutes to supplement a basal infusion rate of 5 ml/hr.

Measurements and Main Results: The total intraoperative dosages of alfentanil, midazolam, and propofol were 2.7 ± 1.1 mg, 4.7 ± 2.7 mg, and 114 ± 42 mg, respectively, for procedures lasting 48 ± 28 minutes to 51 ± 19 minutes (means ± SD). Propofol produced more pain on injection (39% vs. 4% and 6% in the alfentanil and midazolam groups, respectively). Episodes of arterial oxygen saturation less than 90% were more frequent with alfentanil (28%) than with midazolam (3%) or propofol (13%). Using the visual analog scale, patients reported comparable levels of discomfort, anxiety, and sedation during the operation in all three treatment groups. Postoperative picture recall was significantly decreased with midazolam versus alfentanil and propofol. Finally, postoperative nausea was reported more frequently in the alfentanil group (29%) than in the midazolam (10%) or propofol (18%) groups, contributing to a significant prolongation of the discharge time in the alfentanil-treated patients.

Conclusions: When self-administered as adjuvants during local anesthesia using a PCA delivery system, alfentanil, midazolam, and propofol were equally acceptable to patients. However, propofol and midazolam were associated with fewer perioperative complications than was alfentanil.     

Clinical evaluation of leukocyte-depleted blood cardioplegia for pediatric open heart operation

Background. Blood cardioplegia (BCP) is widely used for myocardial protection during open heart operation. However, BCP may have a chance to induce neutrophil-mediated myocardial injury during aortic cross-clamping. We clinically evaluated the myocardial protective effect of leukocyte-depleted blood cardioplegia (LDBCP) for initial and intermittent BCP administration in pediatric patients.

Methods. Fifty patients undergoing open heart operation for congenital heart disease between January 1997 and March 1999 were reviewed. Twenty-five were administered LDBCP for myocardial protection during ischemic periods (LDBCP group), and the remaining 25 were given BCP without leukocyte depletion (BCP group).

Results. The difference in plasma concentrations of malondialdehyde between coronary sinus effluent blood and arterial blood just after reperfusion in the LDBCP group (1.68 ± 0.56 μmol/L) was significantly lower than that in the BCP group (2.35 ± 0.62 μmol/L; p < 0.01). The LDBCP group showed significantly lower plasma concentrations of human heart fatty acid-binding protein at 50 minutes after reperfusion (LDBCP group, 103.5 ± 38.7 IU/L; BCP group, 144.8 ± 48.8 IU/L; p < 0.01) and the peak value of creatine kinase-MB during the first 24 postoperative hours (LDBCP group, 17.0 ± 8.5 IU/L; BCP group, 26.0 ± 11.6 IU/L; p < 0.01) than did the BCP group. The maximum dose of catecholamine was significantly smaller in the LDBCP group (LDBCP group, 3.20 ± 2.18 μg · kg⁻¹ · min⁻¹; BCP group, 5.60 ± 2.83 μg · kg⁻¹· min⁻¹; p < 0.01).

Conclusions. These results suggest the usefulness of LDBCP for protection from the myocardial injury that can be induced by BCP administration during aortic cross-clamping.     

Bradykinin protects the rabbit heart after cardioplegic ischemia via NO-dependent pathways

Background. Depressed myocardial performance is an important clinical problem after open heart surgery. We hypothesized pretreating with bradykinin would pharmacologically precondition the heart and improve postischemic performance, and induce myocardial preconditioning by activating nitric oxide synthase.

Methods. Thirty-three rabbit hearts underwent retrograde perfusion with Krebs-Henseleit buffer (KHB) followed by 50 minutes of 37°C cardioplegic ischemia with St. Thomas’ cardioplegia solution (StTCP). Ten control hearts received no pretreatment. Ten bradykinin-pretreated hearts received a 10-minute infusion of 0.1 μMol/L bradykinin-enriched KHB and cardioplegic arrest with 0.1 μMol/L bradykinin-enriched StTCP. Six other hearts received 0.1 μMol/L HOE 140, a selective B2 receptor antagonist, added to both the 0.1 μMol/L bradykinin-enriched KHB and 0.1 μMol/L bradykinin-enriched StTCP solutions. Finally, six other hearts received 100 μMol/L of N-Ω-nitro- -arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, added to both the 0.1 μMol/L bradykinin-enriched KHB and 0.1 μMol/L bradykinin-enriched StTCP solutions.

Results. Bradykinin pretreatment significantly improved postischemic performance and coronary flow (CF) compared with control (LVDP: 53 ± 5* vs 27 ± 4 mm Hg; +dP/dt_max: 1,025 ± 93* vs 507 ± 85 mm Hg/s; CF: 31 ± 3* vs 22 ± 2 mL/min; *p < 0.05). Both HOE 140 and L-NAME abolished bradykinin-induced protection, resulting in recovery equivalent to untreated controls.

Conclusions. Bradykinin pretreatment improves recovery of ventricular and coronary vascular function via nitric oxide-dependent mechanisms. Pharmacologic preconditioning by bradykinin pretreatment may be an important new strategy for improving myocardial protection during heart surgery.     

Delayed impairment of cerebral oxygenation after deep hypothermic circulatory arrest in children

Background. Clinical studies of deep hypothermic circulatory arrest (DHCA) have focused only on the immediate postoperative period. However, experimental findings suggest impairment of cerebral oxygenation at 2 to 8 hours after reperfusion.

Methods. In 10 children who had DHCA for heart operations, transcerebral differences of hemoglobin oxygen saturation and plasma hypoxanthine, xanthine, and lactoferrin concentrations were measured in concurrently obtained cerebral venous, arterial, and mixed venous samples up to 10 hours postoperatively.

Results. Compared with preoperative levels (57% ± 7%), cerebral venous oxygen saturation was not significantly reduced until 2 hours (44% ± 6%) and 6 hours (42% ± 5%) after DHCA (p < 0.05). A statistically significant transcerebral (ie, cerebral vein versus artery) concentration difference of hypoxanthine was observed at 30 minutes (3.6 ± 0.9 μmol/L), 1 hour (3.4 ± 1.1 μmol/L), and 2 hours (3.1 ± 0.8 μmol/L) after DHCA but not preoperatively (0.4 ± 0.2 μmol/L). A transcerebral concentration difference of lactoferrin occurred 30 minutes after DHCA (196 ± 70 μg/mL) but not preoperatively (16 ± 20 μg/mL).

Conclusions. Cerebral venous oxygen saturation of hemoglobin decreased as late as 2 to 6 hours after DHCA, in association with impaired cerebral energy status. Neutrophil activation in the cerebral circulation occurred 30 minutes after reperfusion.     

Onset and recovery of neuromuscular blockade after two doses of rocuronium in children

Study Objective: To determine if 450 μg/kg (1.5 times the ED₉₅) of rocuronium would result in a comparable onset with a shorter duration of action when compared with 600 μg/kg (2 times the ED₉₅).

Design: Randomized, single-blind study.

Setting: Teaching hospital.

Patients: 85 ASA physical status I and II children ages 2 through 12, undergoing elective surgery with an inhalation induction using halothane.

Interventions: Group 1 received 600 μg/kg rocuronium, and Group 2 received 450 μg/kg rocuronium.

Measurements and Main Results: The two groups were compared using a Student’s t-test, with p < 0.05 significant. The time of onset, or time to 95% suppression of neuromuscular twitch with standard errors, was 140 ± 13 seconds (range 46 to 365 sec) in Group 1 and 148 ± 13 seconds (range 82 to 345 sec) in Group 2 (NS = not significant). The times to 25% return of twitch from baseline (T₂₅) in Groups 1 and 2 were 28 ± 1.5 minutes (range 14 to 45 min) and 26 ± 1.6 minutes (range 10 to 55 min), respectively (NS). The differences between these two doses in onset of, and recovery from, block were not found to be statistically significant. The results, however, excluded 5% of the higher dose group and 31% of the lower dose group who did not achieve 95% suppression of twitch. Time to maximal suppression of neuromuscular blockade, however, was not statistically significant for the 85 patients with a time of 270 ± 28 seconds (range 91 to 605 sec) with a mean maximal suppression of 98.7% in Group 1 and 313 ± 25 seconds (range 91 to 899 sec) with a mean maximal suppression of 93.1% in Group 2.

Conclusion: The two doses of rocuronium did not differ statistically in onset or duration. Rocuronium at 600 μg/kg offers more reliability than 450 μg/kg in achieving adequate muscle relaxation, and the lower dose may result in a significantly large number of patients who may have inadequate intubating conditions.     

Effect of Low-Dose Positive Inotropic Drugs on Human Internal Mammary Artery Flow

Background. Dobutamine (a β-receptor agonist), enoximone (a type III selective phosphodiesterase inhibitor), and epinephrine (an - and β-mimetic) frequently are used in the perioperative management of patients undergoing coronary artery bypass grafting.

Methods. We performed a double-blind clinical study to compare the effects on internal mammary artery free flow of low doses of these three positive inotropic drugs. Thirty patients in whom the left internal mammary artery was used for coronary artery bypass grafting were randomized into three groups. Internal mammary artery free flow and hemodynamic measurements were evaluated before and 10 minutes after the intravenous infusion of dobutamine (3 μg · kg⁻¹ · min⁻¹), enoximone (200 μg/kg), or epinephrine (0.05 μg · kg⁻¹ · min⁻¹).

Results. A significant increase in free flow occurred only in the dobutamine group (33 ± 7.5 and 42.2 ± 7.9 mL/min before and after drug infusion, respectively; p = 0.013). Comparison of the increase in flow between the groups, however, showed no difference. These drugs, at doses designed to produce a positive inotropic effect, caused little increase in the free flow of the internal mammary artery.

Conclusions. The use of dobutamine, enoximone, and epinephrine as low-dose positive inotropic treatments in the perioperative and postoperative periods of coronary artery bypass grafting should depend on their positive inotropic effects rather than their vasodilative effects on the arterial grafts.     

Combined popliteal and posterior cutaneous nerve of the thigh blocks for short saphenous vein stripping in outpatients: An alternative to spinal anesthesia

Study Objective: To compare a combination of peripheral nerve blocks with spinal anesthesia in ambulatory patients undergoing short saphenous vein stripping.

Design: Prospective, randomized study.

Setting: University hospital.

Patients: 28 ASA physical status I and II ambulatory surgery patients undergoing short saphenous vein stripping.

Interventions: 14 patients received a popliteal block (sciatic nerve block at the popliteal fossa) using 30 ml of alkalinized 3 % chloroprocaine and a posterior cutaneous nerve of the thigh block with 10 ml of 1% lidocaine. The 14 patients who were randomized to the spinal anesthesia group received 65 mg of 5% hyperbaric lidocaine.

Measurements and Main Results: There were no significant differences in age and gender between the two groups (mean age 53 ± 13 years, 8 men and 20 women). Patients in the peripheral nerve block group recovered significantly faster in phase 1 of the postanesthesia care unit (PACU) (67 ± 10 min vs. 122 ± 50 min, p < 0.01) and were discharged home sooner (222 ± 53 min vs. 294 ± 69 min, p < 0.01) than the patients in the spinal anesthesia group.

Conclusions: The combination of popliteal and posterior cutaneous nerve of the thigh blocks provided adequate anesthesia and a faster recovery profile with a similar subjective acceptance of both anesthetic techniques in ambulatory patients undergoing short saphenous vein stripping in the prone position.     

Genetic dissection of phosphate- and vitamin D-mediated regulation of circulating Fgf23 concentrations

Fibroblast growth factor-23 (FGF23) is a circulating factor that plays critical roles in phosphate and vitamin D metabolism. The goal of our studies was to dissect the pathways directing the vitamin D–phosphate–FGF23 homeostatic axis. To test the role of diet in the regulation of Fgf23, wild-type (WT) mice were fed either a standard (0.44% phosphorus) or a low-phosphate (0.02%) diet. WT mice on standard diet had a serum phosphate of 9.5 ± 0.3 mg/dl and an Fgf23 concentration of 99.0 ± 10.6 pg/ml; mice on the low-phosphate diet had a phosphate of 5.0 ± 0.2 mg/dl (P < 0.01) and an Fgf23 of 10.6 ± 3.7 pg/ml (P < 0.01). To genetically separate the effects of phosphate and vitamin D on Fgf23, we examined vitamin D receptor null (VDR^−/−) mice, which are hypocalcemic and hypophosphatemic secondary to hyperparathyroidism. On standard diets, WT and VDR^+/− mice had Fgf23 levels of 106.0 ± 30.7 and 90.6 ± 17.3 pg/ml, respectively, whereas Fgf23 was undetectable in the VDR^−/−. Animals were then placed on a diet that normalizes serum calcium and phosphorus. This ‘rescue’ increased Fgf23 in WT to 192.3 ± 32.5 pg/ml and in VDR^+/− to 388.2 ± 89.6pg/ml, and importantly, in VDR^−/− to 476.9 ± 60.1 pg/ml (P < 0.01 vs. WT). In addition, renal vitamin D 1-alpha hydroxylase (1-OHase) mRNA levels were corrected to WT levels in the VDR^−/− mice. In summary, Fgf23 is suppressed in diet-induced hypophosphatemia and in hypophosphatemia associated with secondary hyperparathyroidism. Normalization of serum phosphate by diet in VDR^−/− mice increases Fgf23. Thus, our results demonstrate that Fgf23 is independently regulated by phosphate and by vitamin D.     

Change of serum growth factors in infants with isolated ventricular defect undergoing surgical repair

Background. Despite increasing clinical use and recent evidence that insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and human growth hormone (hGH) target the heart, the clinical manifestations following the change in the serum growth factors in infants with isolated ventricular septal defect (VSD) undergoing surgical repair have not been clearly defined.

Methods. Twenty normal infants (group I) and 44 consecutive infants with echocardiography established isolated VSD (aged from 3 months to 1 year; body weight from 6.0 ± 1.8 kg to 8.2 ± 1.6 kg) were investigated. Among 44 infants with VSD, 20 with shunt fraction, Qp/Qs ≤1.5 were free of symptoms of congestive heart failure (group II); 24 with shunt fraction, Qp/Qs ≥2.0 were in congestive heart failure (group IIIa); and 20 of these 24 infants had undergone VSD repair 6 months before their second study (group IIIb). Serum IGF-1, IGFBP-3, and hGH factors were determined by enzyme-linked immunosorbent assay using a monoclonal antibody.

Results. The serum levels of IGF-1, IGFBP-3, and hGH factors were 111.9 ± 2.3 ng/mL, 22.0 ± 2.3 ng/mL, and 3.6 ± 0.7 μIU/mL for group I; 63.8 ± 8.2 ng/mL, 17.1 ± 1.6 ng/mL, and 4.1 ± 1.2 μIU/mL for group II; 24.0 ± 2.6 ng/mL, 9.4 ± 0.7 ng/mL, and 14.7 ± 3.5 μIU/mL for group IIIa; 79.4 ± 12 ng/mL, 20.3 ± 1.3 ng/mL, and 4.3 ± 0.7 μIU/mL for group IIIb. In comparison to group I, the decrease in serum levels of IGF-1 and IGFBP-3 in groups II and IIIa were statistically significant (in group II 43% and 32%, p < 0.05; in group IIIa 79% and 37%, p < 0.01). Also the increase in serum level of hGH concentration in group IIIa was significant (increased threefold, p < 0.01). Interestingly, the change in serum levels of IGF-1, IGFBP-3 (decrease), and hGH (increase), returned to the normal range of serum levels after VSD repair in group IIIb. All congestive heart failure symptoms subsided in group IIIb during follow-up.

Conclusions. Improvement in serum levels of IGF-1, IGFBP-3, and hGH were identified in infants with VSD after surgical repair.     

Intravenous Phenylephrine Preconditioning of Cardiac Grafts From Non–Heart-Beating Donors

Background. Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heart-beating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning.

Methods. Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 μg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia.

Results. Phenylephrine 25 μg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 ± 0.5 versus 7.7 ± 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 ± 5.3 versus 41.0 ± 3.4 mm Hg; p = 0.04). Phenylephrine 25 μg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09).

Conclusions. Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.     

Heparin-Bonded Circuits Decrease Myocardial Ischemic Damage: An Experimental Study

Background. Heparin-bonded cardiopulmonary bypass circuits reduce complement activation, but their effect on myocardial function is unknown. This study was undertaken to determine whether heparin-bonded circuits reduce myocardial damage during acute surgical revascularization.

Methods. In 16 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, all animals were placed on percutaneous bypass followed by standard cardiopulmonary bypass during the periods of cardioplegic arrest and reperfusion. In 8 pigs, heparin-bonded circuits were used, whereas 8 other pigs received nonbonded circuits.

Results. Animals treated with heparin-bonded circuits had the best preservation of wall motion scores (3.5 ± 0.3 versus 2.3 ± 0.2; 4 = normal to −1 = dyskinesis; p < 0.05), least tissue acidosis (change in pH = −0.31 ± 0.02 versus −0.64 ± 0.08; p < 0.05), smallest increase in lung H₂O (1.7% ± 0.7% versus 6.1% ± .5%; p < 0.05), and the lowest area of necrosis/area of risk (20.3% ± 2.2% versus 40.4% ± 1.6%; p < 0.05).

Conclusions. We conclude that heparin-bonded circuits significantly decrease myocardial ischemic damage during acute surgical revascularization.     

Pre- and postoperative exercise capacity associated with hemodynamics in adult patients with atrial septal defect: A retrospective study

Objective: This study evaluated the pre- and postoperative exercise capacity in adult patients with atrial septal defect (ASD) associated with hemodynamic variables. Methods: Adults (70) with ASD underwent symptom-limited exercise tests. Peak O₂ uptake (Peak VO₂) and % peak VO₂, that is the percentage of predicted value, were measured. These patients were divided into three groups according to pulmonary-to-systemic flow ratio (Qp/Qs) and systolic pulmonary arterial pressure (PAs); Group A: Qp/Qs3, PAs50 mm Hg, Group B: Qp/Qs>3, any PAs, Group C: Qp/Qs3, PAs>50 mm Hg. Exercise test was repeated in 22 patients after surgical closure of ASD (mean 4.6±2.0 months). Results: Peak VO₂ was significantly lower in group B (P<0.01) and group C (P<0.01) than in group A (19.3±5.7, 17.6±3.6, 27.6±6.3 ml/min/kg, respectively). In patients except those in group C, there were a weak negative correlation between PAs and % peak VO₂ (r=0.61) and a significant negative correlation between Qp/Qs and % peak VO₂ (r=0.86). Postoperative peak VO₂ increased significantly in group A (27.2±5.1–31.1±5.1 ml/min/kg, P<0.05) and group B (16.7±3.3–21.5±2.1 ml/min/kg, P<0.01). However, there was no significant difference between pre- and postoperafive peak VO₂ in group C (16.8±1.3–17.8±2.8 ml/min/kg, NS). Conclusions: In ASD patients except those with small or moderate left-to-right shunt and high pulmonary arterial pressure, there was a significant negative correlafion between Qp/Qs and peak VO₂ corrected by age and gender. Patients with large left-to-right shunt and/or high pulmonary arterial pressure had reduced exercise capacity. However, exercise capacity in patients with large left-to-right shunt increased after closure of ASD regardless of whether they had high pulmonary arterial pressure.     

Cytostatic Lung Perfusion by Use of an Endovascular Blood Flow Occlusion Technique

Background. Different modalities of cytostatic lung perfusion were compared regarding plasma and tissue drug concentrations to assess the efficacy of an endovascular blood flow occlusion technique.

Methods. A cytostatic lung perfusion study with doxorubicin hydrochloride was performed on large white pigs (n = 12). Plasma and tissue concentrations of doxorubicin were compared for isolated lung perfusion with open cannulation (ILP), blood flow occlusion perfusion with open cannulation of the pulmonary artery alone (BFO), and intravenous drug administration (IV). In a fourth group, thoracotomy-free BFO perfusion was performed by endovascular balloon catheterization of the pulmonary artery (endovascular BFO). The 3 animals in this group were used to compare the doxorubicin-perfused pulmonary tissue with the contralateral nonperfused lobes after 1 month.

Results. The mean lung tissue doxorubicin concentration at the end of perfusion was 19.8 ± 1.6 μg/g after ILP, 27.6 ± 2.2 μg/g after BFO (p = not significant), and 3.0 ± 0.8 μg/g after IV perfusion (p < 0.01). Whereas doxorubicin was not detectable in the plasma in the ILP group, concentrations ranged from not detectable to 0.44 μg/mL in the BFO group and from 0.31 to 0.84 μg/mL in the IV group (p < 0.05). Mean myocardial tissue concentration was not significantly different after BFO than IV perfusion (1.1 ± 0.5 μg/g and 1.8 ± 0.1 μg/g, respectively). In the endovascular BFO group, balloon-blocked pulmonary artery perfusion was successfully performed in all animals, and after 1 month, lung tissue showed no cytostatic-induced histologic changes.

Conclusions. Compared with ILP, BFO cytostatic lung perfusion produced an insignificantly higher lung-tissue concentration, corresponding to a sixfold to ninefold higher level than after IV perfusion. Plasma drug levels during BFO perfusion were lower than during IV perfusion. Endovascular BFO may be a promising technique for repeated cytostatic lung perfusion.     

Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia

Background. Therapeutic angiogenesis in ischemic myocardium has been shown to be a feasible and effective strategy to improve regional blood flow and myocardial function. However, the optimal mode of growth factor administration still needs to be established.

Methods. Using a pig model of chronic myocardial ischemia, we evaluated the efficacy of intravenous and intracoronary infusion of FGF-2 at 2 and 6 μg/kg compared with a vehicle control. Improvement in myocardial perfusion and function was assessed by angiography, colored microspheres, and function and perfusion magnetic resonance imaging.

Results. Intracoronary 6-μg/kg FGF-2 increased angiographic collaterals (p = 0.046) and increased regional blood flow to the ischemic area from 0.36 ± 0.07 to 0.59 ± 0.08 mL/min/g at stress (vs control, p = 0.032). Also, after 6 μg/kg intracoronary FGF-2, ejection fraction, regional wall motion, and thickening improved significantly by 9.9% ± 1.9%, 126% ± 39%, and 13.8% ± 3.6%, respectively. Intravenous FGF-2 and intracoronary 2 μg/kg FGF-2 were ineffective.

Conclusions. A single 6-μg/kg intracoronary treatment with FGF-2 resulted in significant improvement in collateralization and regional and global function of chronically ischemic myocardium. Single intravenous infusion of FGF-2 was not effective in this model.     

Recovery following outpatient anesthesia: Use of enflurane versus propofol

Study Objective: To compare the intraoperative conditions and postoperative recovery of patients following the use of either propofol-nitrous oxide (N₂O) or enfurane-N₂O for maintenance of outpatient anesthesia.

Design: Randomized, single-blind study.

Setting: University hospital outpatient surgery center.

Patients: 61 ASA physical status I and II, healthy female outpatients undergoing laparoscopic surgery.

Interventions: Patients were randomly assigned to one of three anesthetic regimes. Group 1 (control) received thiopental sodium 4 mg/kg intravenously (IV), followed by 0.5% to 1.5% enfurane and 67% N₂0 in oxygen (O₂). Group 2 received propofol 2 mg/kg IV, followed by 0.5% to 1.5% enfurane and 67% N₂O in O₂. Group 3 received propofol 2 mg/kg IV, followed by propofol 50 to 160 μg/kg/min IV and 67% N₂O in O₂. All patients received succinylcholine 1 mglkg IV to facilitate tracheal intubation and atracurium 10 to 20 mg IV to provide adequate relaxation during the maintenance period.

Measurements and Main Results: Recovery from anesthesia was assessed by a research nurse who was unaware of the anesthetic technique used. The mean ± SD time to eye opening was significantly longer in the thiopental-enflurane-N₂O group (Group 1) than in the propofol-propofol-N₂0 group (Group 3) (6.1 ± 2.5 minutes vs. 3.5 ± 2.8 minutes, respectively). In addition, the mean time to respond to verbal commands was significantly shorter in the propofol induction groups compared with the thiopental induction group. However, the use of enfurane versus propofol for maintenance of anesthesia did not significantly prolong the time from arrival in the recovery room to sitting, tolerating oral fluids, walking, or being judged “fit for discharge.” There were no differences among the three groups with respect to postoperative pain or analgesic requirements. Finally, patients who received enfurane for maintenance of anesthesia had a significantly higher frequency of nausea and vomiting than the propofol maintenance group.

Conclusion: Induction of anesthesia with propofol is associated with a more rapid emergence from anesthesia than induction with thiopental. Maintenance of anesthesia with enfurane did not prolong recovery compared with maintenance with propofol, but enfurane was associated with increased frequency of postoperative nausea and vomiting.     

The effects of preanesthetic oral clonidine on total requirement of propofol for general anesthesia

Study Objective: To investigate the effects of preanesthetic oral clonidine on total propofol requirement for uniform minor surgery (breast conservative surgery: breast cancer removal with axillary lymph node dissection), and to compare the action of clonidine with that of preanesthetic oral diazepam, a commonly used benzodiazepine.

Design: Randomized double-blinded study.

Setting: Operating room ASA physical status I and II room and recovery room of the cancer center.

Patients: 80 breast cancer patients scheduled for surgery.

Interventions: Patients were randomized to one of four treatment groups (placebo, clonidine 75 μg, or 150 μg of clonidine, or 10 mg of diazepam were orally administered 60 min before induction of anesthesia); n = 20 per group. After evaluating the sedation and anxiety levels of patients using a visual analog scale, anesthesia was induced with propofol (1.5 mg/kg), and maintained with oxygen (O₂): nitrous oxide (N₂O) (30:70) with a continuous infusion of propofol. The propofol infusion was started at 10 mg/kg/h for 10 minutes, then decreased to 8 mg/kg/h, and 6 mg/kg/h thereafter, and the rate of infusion was adjusted to obtain adequate anesthesia (maintaining hemodynamic parameters within 20% of that prior to premedication). Fentanyl 0.2 mg (each 0.1 mg was given for intubation and axillary lymph node dissection, respectively) was administered.

Measurements and Main Results: Preanesthetic oral clonidine (150 μg) and diazepam (10 mg) induced anxiolysis without sedation. The total requirement (the mean infusion rates) of propofol in placebo, clonidine 75 μg, clonidine 150 μg, and 10 mg of diazepam groups were 841 ± 70 (9.0 ± 0.3), 720 ± 63 (7.1 ± 0.4), 491 ± 39 (5.6 ± 0.2), and 829 ± 77 mg (7.9 ± 0.4 mg/kg/h), respectively. The cost of propofol in these groups was $51.0 ± 3.8, $45.5 ± 3.2, $33.5 ± 2.3, and $50.5 ± 4.4, respectively.

Conclusions: Preanesthetic oral clonidine (150 μg) but not diazepam (10 mg) reduced the total requirement of propofol while stabilizing hemodynamic parameters. In addition, 150 μg of oral clonidine attenuates the hemodynamic responses associated with tracheal intubation.     

Warm reperfusion and myocardial protection

Background. The aim of this study was to determine whether warm reperfusion improves myocardial protection with cardiac troponin I as the criteria for evaluating the adequacy of myocardial protection.

Methods. One hundred five patients undergoing first-time elective coronary bypass surgery were randomized to one of three cardioplegic strategies of either (1) cold crystalloid cardioplegia followed by warm reperfusion, (2) cold blood cardioplegia followed by warm reperfusion, or (3) cold blood cardioplegia with no reperfusion.

Results. The total amount of cardiac troponin I released tended to be higher in the cold blood cardioplegia with no reperfusion group (3.9 ± 5.7 μg) than in the cold blood cardioplegia followed by warm reperfusion group (2.8 ± 2.7 μg) or the cold crystalloid cardioplegia followed by warm reperfusion group (2.8 ± 2.2 μg), but not significantly so. Cardiac troponin I concentration did not differ for any sample in any of the three groups.

Conclusions. Our study showed that the addition of warm reperfusion to cold blood cardioplegia offers no advantage in a low-risk patient group.     

S100β after coronary artery surgery: release pattern, source of contamination, and relation to neuropsychological outcome

Background. S100β has been suggested as a marker of brain damage after cardiac operation. The aim of this study was to characterize the early S100β release in detail and relate it to neuropsychological outcome.

Methods. Three groups of patients were investigated. All patients underwent coronary artery bypass surgery (CABG) with extracorporeal circulation. In group A, 110 patients had sampling of S100β for the first 10 postoperative hours and also underwent neuropsychological testing. In group B, 14 patients were examined for the effect of autotransfusion on S100β levels. Eight patients in group C had their intraoperative bleeding processed with a cell-saving device.

Results. Group A had a heterogeneous release pattern with several rapid elevations in S100β concentration. In group B, high concentrations of S100β were found in the autotransfusion blood (range 0.2 to 210 μg/L) with a concurrent elevation of serum S100β levels after transfusion of shed blood. In group C, high levels of S100β were found in the blood from the surgical field (12.0 ± 6.0 μg/L) and decreased (1.1 ± 0.64 μg/L) after wash. Group C had significantly lower S100β values at the end of cardiopulmonary bypass compared to group A (0.53 ± 0.35 μg/L versus 2.40 ± 1.5 μg/L). S100β values were corrected for extracerebral contamination with a kinetic model. With this correction, an association was found between adverse neuropsychological outcome and S100β release in group A (r = 0.39, p < 0.02).

Conclusions. A significant amount of S100β is found both in the blood from the surgical field and in the shed mediastinal blood postoperatively. Infusion of this blood will result in infusion of S100β into the blood and interfere in the interpretation of early systemic S100β values.