B.Hugh Dorman

Clonidine improves perioperative myocardial ischemia, reduces anesthetic requirement, and alters hemodynamic parameters in patients undergoing coronary artery bypass surgery

The purpose of this study was to determine if clonidine reduces myocardial ischemia or alters anesthetic requirement and perioperative hemodynamic parameters during coronary artery bypass grafting (CABG) surgery. Forty-three patients were randomized in a prospective, double-blind fashion to receive either clonidine (5 micrograms/kg) or placebo. Anesthetic induction and maintenance was accomplished with intravenous sufentanil-midazolam (S-M) in a 1:20 ratio; up to 1.0% enflurane was added during surgery when repeated boluses of S-M failed to maintain the blood pressure within 20% of preinduction values. Continuous ST segment analysis of leads II and V5 was performed throughout surgery with maximal ST segment deflection from baseline recorded every 5 minutes. Catecholamine levels were measured intermittently throughout the perioperative period and myocardial lactate use or excretion was determined just prior to cardiopulmonary bypass (CPB) and at 1, 5, 10, 30, and 60 minutes after release of the aortic cross-clamp. Patients who received clonidine required significantly less sufentanil for their surgical procedure (11.82 +/- 0.66 micrograms/kg v 14.55 +/- 0.90 micrograms/kg, P < 0.05) and also needed less enflurane for blood pressure control, particularly during CPB (P < 0.05). Baseline hemodynamic parameters were similar for both groups prior to induction. In the period between anesthetic induction and the initiation of CPB, patients treated with clonidine had a significantly slower heart rate (HR) (P < 0.01), a lower cardiac output (CO) (P < 0.05), and transiently higher systemic vascular resistance (SVR) (P < 0.05) than placebo-treated patients. Immediately after CPB, patients receiving clonidine continued to have a significantly lower CO (P < 0.01) and a higher SVR (P < 0.01) than placebo-treated patients. Clonidine treatment significantly increased the percentage of patients who required pacing after CPB (P < 0.05). In the intensive care unit, clonidine-treated patients displayed a persistently increased requirement for pacing (P < 0.01), decreased systolic blood pressures, and reduced sodium nitroprusside requirements relative to patients treated with placebo. Epinephrine and norepinephrine levels were lower in clonidine-treated patients throughout the perioperative procedure with significant differences noted immediately following sternotomy and release of the aortic cross-clamp (P < 0.05). Critical ST segment depression was significantly less in clonidine-treated patients for the period from sternotomy until application of the aortic cross-clamp (P < 0.01). Following CPB, absolute deviation of ST segments from isoelectric baseline was significantly less in the clonidine-treated group (P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Magnesium supplementation in the prevention of arrhythmias in pediatric patients undergoing surgery for congenital heart defects

Abstract Background The efficacy of magnesium in the prevention of arrhythmias in pediatric patients after heart surgery remains unknown. Therefore we prospectively examined the effect of magnesium treatment on the incidence of postoperative arrhythmias in pediatric patients undergoing surgical repair of congenital heart defects. Methods and Results Twenty-eight pediatric patients undergoing heart surgery with cardiopulmonary bypass were prospectively, randomly assigned in a double-blind fashion to receive intravenous magnesium (magnesium group, n=13; 30 mg/kg) or saline (placebo group, n=15) immediately after cessation of cardiopulmonary bypass. Magnesium, potassium, and calcium levels were measured at defined intervals during surgery and 24 hours after surgery. Continuous electrocardiographic documentation by Halter monitor was performed for 24 hours after surgery. Magnesium levels were significantly decreased below the normal reference range for patients in the placebo group compared with the magnesium group on arrival in the intensive care unit and for 20 hours after surgery. Magnesium levels remained in the normal range for patients in the magnesium group after magnesium supplementation. In 4 patients in the placebo group (27%), junctional ectopic tachycardia developed within the initial 20 hours in the intensive care unit. No junctional ectopic tachycardia was observed in the magnesium group ( P = .026). Conclusions Although this study was originally targeted to include 100 patients, the protocol was terminated because of the unacceptable incidence of hemodynamically significant junctional ectopic tachycardia that was present in the placebo group. Thus low magnesium levels in pediatric patients undergoing heart surgery are associated with an increased incidence of junctional ectopic tachycardia in the immediate postoperative period.

Cardiopulmonary bypass induces the synthesis and release of matrix metalloproteinases

BACKGROUND A number of cellular and molecular events can be induced after cardiac procedures requiring cardiopulmonary bypass (CPB). The matrix metalloproteinases (MMPs) are a recently discovered family of enzymes that degrade the extracellular matrix, but expression during and after CPB is unknown. METHODS Systemic plasma MMP levels were measured in patients (n = 28, 63 +/- 1 years) undergoing elective coronary revascularization requiring CPB at baseline, termination of CPB, and 30 minutes, 6 and 24 hours after CPB. Representative classes of MMP species known to degrade matrix and basement membrane components were selected for study. Specifically, the interstitial collagenases MMP-8 and MMP-13, and the gelatinases MMP-2 and MMP-9 were determined by internally validated enzyme-linked immunosorbent assay. RESULTS The MMP-8 levels increased by fourfold at separation from CPB, and returned to within normal values within 30 minutes after CPB. The proenzyme forms of MMP-13 and MMP-9 increased by more than twofold at cross-clamp release and returned within normal limits within 6 hours after CPB. The proform of MMP-2 increased from baseline values at 6 and 24 hours postoperatively; likely indicative of de novo synthesis. CONCLUSIONS A specific portfolio of MMPs are released and synthesized during and after CPB. Because MMPs can degrade extracellular proteins essential for maintaining normal cellular architecture and function, enhanced MMP release and activation may contribute to alterations in tissue homeostasis in the early postoperative period.

Mechanisms of right ventricular dysfunction after pulmonary resection

BACKGROUND Significant right ventricular (RV) dysfunction as measured by increased end-diastolic volume and reduced ejection fraction has been documented in the postoperative period after pulmonary resection. We hypothesized that changes in RV contractile state or afterload may contribute to this RV pump dysfunction. METHODS In part one of the study, RV preload was altered on postoperative day 2 (n = 6) by rapid infusion of Hespan to a total of 250, 500, and 1,000 mL. The relationship between RV stroke work and end-diastolic volume was plotted using linear regression. This preload recruitable stroke work relation had been previously validated as a load-insensitive index of RV contractility. The slopes of the preoperative relation (n = 35) and postoperative relation were compared. In part two of the study, RV afterload was reduced by continuous infusion of prostaglandin E1 (n = 6) through postoperative day 2 and RV pump function was assessed. RESULTS Comparison of the slopes of the preload recruitable stroke work relation plotted preoperatively and on postoperative day 2 revealed no significant difference, indicating no change in RV contractile state. Infusion of prostaglandin E1 in the postoperative period (n = 6) significantly reduced pulmonary vascular resistance (3.67 +/- 0.19 versus baseline 5.72 +/- 0.19 dyne . s . cm-5/ m2; p < 0.05). However, RV ejection fraction remained significantly reduced (0.34 +/- 0.01 versus baseline 0.42 +/- 0.01; p < 0.05) and end-diastolic volume significantly increased (105 +/- 5 versus baseline 93 +/- 2 mL/m2; p < 0.05). Heart rate was increased compared with baseline throughout the postoperative period. CONCLUSIONS The present study suggests that RV dysfunction after pulmonary resection is not caused by primary alterations in contractility or immediate changes in afterload. Better control of heart rate with minimal effect on inotropy may enhance RV pump function.

Complete brachial plexus palsy after total shoulder arthroplasty done with interscalene block anesthesia

Background and Objectives: This report illustrates that brachial plexus palsy can result from either interscalene block or total shoulder arthroplasty. It is often impossible to determine which procedure caused the deficit; therefore, we believe the focus should be placed on treatment of the neurologic deficit. This report provides a suggested algorithm for diagnosis and treatment of postprocedure brachial plexus palsy. Methods: Interscalene block was used as the operative anesthetic for our patients total shoulder arthroplasty. Complete brachial plexus palsy was diagnosed postoperatively. Results: The patients postoperative treatment and recovery are described. Conclusions: Proper diagnosis and treatment of postprocedure brachial plexus palsy may improve recovery of function. Several precautions may reduce the likelihood of brachial plexus palsy following interscalene block for total shoulder arthroplasty.

Differential effects of calcium channel antagonists in the amelioration of radial artery vasospasm

BACKGROUND Radial artery (RA) is being used for coronary artery bypass grafting (CABG) with greater frequency. However, RA is prone to post-CABG vasospasm, which may be neurohormonally mediated. Use of the calcium channel antagonist diltiazem has been advocated as a strategy to reduce post-CABG RA vasospasm. However, whether and to what degree different calcium channel antagonists influence neurohormonally induced RA vasoconstriction remains unknown. METHODS RA segments were collected from patients undergoing elective CABG (n = 13), and isometric tension was examined in the presence of endothelin (10 nM) or norepinephrine (1 microM). In matched RA, endothelin- or norepinephrine-induced contractions were measured in the presence of diltiazem (277 nM), amlodipine (73 nM), or nifedipine (145 nM). These concentrations of calcium channel antagonists were based upon clinical plasma profiles. RESULTS Endothelin and norepinephrine caused a significant increase in RA-developed tension (0.54+/-0.1 and 0.68+/-0.1 g/mg, respectively; p<0.05). Amlodipine or nifedipine significantly reduced RA vasoconstriction in the presence of endothelin (30+/-6% and 41+/-9%, respectively; p<0.05) or norepinephrine (27+/-8% and 53+/-9%, respectively; p<0.05), whereas diltiazem did not significantly reduce RA vasoconstriction. CONCLUSIONS These results demonstrate that neurohormonal factors released post-CABG can cause RA vasoconstriction, and that calcium channel antagonists are not equally effective in abrogating that response. Both amlodipine and nifedipine, which have a higher degree of vascular selectivity, appear to be the most effective in reducing RA vasoconstriction.

A comparison of wound instillation and caudal block for analgesia following pediatric inguinal herniorrhaphy

Regional analgesia, in a variety of forms, has been shown to afford effective postoperative pain relief after pediatric inguinal hernia repair. This study compares the efficacy of wound instillation with 0.25% bupivacaine (n = 20), caudal block with 0.25% bupivacaine (n = 35), and a control group (n = 15). Outcome parameters examined include total operating room time, time to extubation, postoperative objective pain scales, and requirement for supplemental analgesics. Patients who received caudal blocks had significantly decreased emergence times (P < .002), exhibited fewer pain-related behaviors postoperatively (P < .0025), and required less narcotic to maintain normal hemodynamics (P < .05). Operating room time was not statistically different between the three groups. The use of perioperative analgesic blocks resulted in quicker awakening, a more comfortable postoperative course, and potentially earlier discharge from same-day surgery.

Preservation of Myocyte Contractile Function After Hypothermic Cardioplegic Arrest by Activation of ATP-Sensitive Potassium Channels

BACKGROUND Left ventricular (LV) dysfunction can occur after hyperkalemic cardioplegic arrest and subsequent reperfusion and rewarming. Activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels within the myocyte sarcolemma has been shown to be cardioprotective for myocardial reperfusion injury and ischemia and may play a contributory role in preconditioning for cardioplegic arrest. Accordingly, the present study tested the hypothesis that cardioplegic arrest and activation of KATP channels by a potassium channel opener (PCO) would attenuate alterations in ionic homeostasis and improve myocyte contractile function. METHODS AND RESULTS Porcine LV myocytes were isolated and randomly assigned to the following treatment groups: normothermic control, incubation in cell culture media for 2 hours at 37 degrees C (n=60); hyperkalemic cardioplegia, incubation for 2 hours in hypothermic hyperkalemic cardioplegic solution (n=60); or PCO/cardioplegia, incubation in cardioplegic solution containing 100 micromol/L of the PCO aprikalim (n=60). Hyperkalemic cardioplegia and rewarming caused a significant reduction in myocyte velocity of shortening compared with normothermic control values (33+/-2 versus 66+/-2 microm/s, P<.05). Cardioplegic arrest with PCO supplementation significantly improved indices of myocyte contractile function when compared with hyperkalemic cardioplegia (58+/-4 microm/s, P<.05). Myocyte intracellular calcium increased during hyperkalemic cardioplegic arrest compared with baseline values (147+/-2 versus 85+/-2 nmol/L, P<.05). The increase in intracellular calcium was significantly reduced in myocytes exposed to the PCO-supplemented cardioplegic solution (109+/-4 nmol/L, P<.05). CONCLUSIONS Cardioplegic arrest with simultaneous activation of KATP channels preserves myocyte contractile processes and attenuates the accumulation of intracellular calcium. These findings suggest that changes in intracellular calcium play a role in myocyte contractile dysfunction associated with cardioplegic arrest. Moreover, alternative strategies may exist for preservation of myocyte contractile function during cardioplegic arrest.

Tranexamic Acid Reduces Bleeding After Cardiopulmonary Bypass When Compared to Epsilon Aminocaproic Acid and Placebo

Abstract Perioperative bleeding following coronary artery bypass grafting (CABG) is associated with increased blood product usage. Although aprotonin is effective in reducing perioperative blood loss, excessive cost prohibits routine utilization. Epsilon aminocaproic acid (EACA) and tranexamic acid (TA) are inexpensive antifibrinolytic agents, which, when give prophylactically, may reduce blood loss. The present study was undertaken to compare the efficacy of TA and EACA in reducing perioperative blood loss. Methods: The study population consisted of first‐time CABG patients. Patients were allocated in a prospective double‐blind fashion: (1) group EACA (loading dose 150 mg/kg, continuous infusion 10 mg/kg per hour for 6 hours, N = 20); (2) group TA (loading dose 15 mg/kg, continuous infusion 1 mg/kg per hour for 6 hours, N = 20); (3) control group (infusion of normal saline for 6 hours, N = 19). Results: Treatment groups were similar preoperatively. No significant difference in intraoperative blood loss or perioperative use of blood products was noted. D‐dimer concentration was elevated in the control group compared to the EACA and TA groups (p < 0.05). Group TA had less postoperative blood loss than the EACA and control groups at 6 and 12 hours postoperatively (p < 0.05). TA had reduced total blood loss (600 ± 49 mL) postoperatively compared to EACA (961 ± 148 mL) and control (1060 ± 127mL, p < 0.05). Conclusion: TA and EACA effectively inhibited fibrinolytic activity intraoperatively and throughout the first 24 hours postoperatively. TA was more effective in reducing blood loss postoperatively following CABG. This suggests that TA may be beneficial as an effective and inexpensive antifibrinolytic in first‐time CABG patients.

Protamine use during peripheral vascular surgery: A prospective randomized trial

PURPOSE One hundred twenty patients undergoing aortic reconstruction (40), infrainguinal bypass (49), and carotid endarterectomy (31) were prospectively enrolled into a double-blind randomized trial to investigate the utility of routine heparin reversal with protamine. METHODS All patients underwent systemic heparinization with 90 U/kg body weight during operation and after revascularization were randomized to receive either protamine or saline solution for heparin reversal. Blood loss was measured throughout the surgical procedure, and indexes of coagulation and the requirement for blood and blood products were documented during operation and the first 24 hours after operation. RESULTS Plasma heparin concentration, partial thromboplastin time, and activated clotting time were significantly higher (p < 0.05) in those receiving saline solution at 20 minutes and 1 hour after administration. Total surgical blood loss was not significantly different between study groups. No significant differences were found in blood product requirement, intravenous fluid administered, hematocrit, or wound hematomas between groups at 24 hours. In addition, no difference was seen in the surgeons subjective intraoperative assessment of hemostasis after administration of either study drug. Furthermore, after study drug administration protamine was associated with a deleterious effect on subsequent intraoperative blood loss (318 +/- 33 ml vs 195 +/- 18 ml, p < 0.05). CONCLUSIONS Although protamine effectively reverses heparin anticoagulation, its routine use after elective peripheral vascular surgical reconstruction does not appear to provide any clinical benefit.