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1.
Br J Anaesth ; 86(1): 68-76, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11575413

ABSTRACT

Elderly patients may be considered for 'fast-track' cardiac anaesthesia, but can suffer psychological complications and slow recovery of mental function after surgery, which can interfere with recovery. Reduced metabolism and changed distribution of anaesthetic and sedative agents can cause poor recovery. We made a prospective randomized comparison of mental function, haemodynamic stability and extubation and discharge times in elderly patients (65-79 yr) receiving two premedication, anaesthetic and sedative techniques. Patients received either propofol (n=39) (fentanyl 10-15 microg kg(-1) and propofol 2-6 mg kg(-1) intraoperatively and a propofol infusion for 3 h postoperatively) or premedication with lorazepam followed by midazolam for anaesthesia (n=39) (fentanyl 10-15 microg kg(-1) and midazolam 0.05-0.075 mg kg(-1) intraoperatively and a midazolam infusion for 3 h postoperatively). Impairment of mental function was noted in 41% of patients in the propofol group and 83% in the lorazepam and midazolam group (P=0.001) 18 h after extubation. Patients in the propofol group were extubated earlier [1.4 (SD 0.6) vs 1.9 (0.8) h, P=0.02]; and reached standard intensive care unit discharge criteria [7.6 (4.6) vs 14.2 (13) h, P=0.02] and hospital discharge criteria [4.3 (1.0) vs 4.9 (1.1) days, P=0.04) sooner than patients in the lorazepam and midazolam group, but actual discharge times did not differ between the groups. Haemodynamic values were stable in both groups.


Subject(s)
Anesthesia, General/adverse effects , Cognition Disorders/etiology , Coronary Artery Bypass/adverse effects , Aged , Anesthesia, General/methods , Anesthetics, Intravenous/adverse effects , Anti-Anxiety Agents/adverse effects , Consciousness/drug effects , Female , Hemodynamics/drug effects , Humans , Length of Stay , Lorazepam/adverse effects , Male , Midazolam/adverse effects , Postoperative Complications , Propofol/adverse effects , Prospective Studies , Psychometrics
2.
J Clin Invest ; 108(4): 585-90, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11518732

ABSTRACT

The clinical use of doxorubicin, an anthracycline chemotherapeutic agent, is limited by cardiotoxicity, particularly when combined with herceptin, an antibody that blocks the HER2 receptor. Doxorubicin induces cyclooxygenase-2 (COX-2) activity in rat neonatal cardiomyocytes. This expression of COX-2 limits doxorubicin-induced cardiac cell injury, raising the possibility that the administration of a prostaglandin may protect the heart during the in vivo administration of doxorubicin. Doxorubicin (15 mg/kg) administered to adult male Sprague Dawley rats induced COX-2 expression and activity in cardiac tissue. Prostacyclin generation measured as the excretion of 2,3-dinor-6-keto-PGF(1alpha) also increased, and this was blocked by a COX-2 inhibitor, SC236. In contrast, administration of a COX-1 inhibitor SC560 at a dose that reduced serum thromboxane B2 by more than 80% did not prevent the doxorubicin-induced increase in prostacyclin generation. Doxorubicin increased cardiac injury, detected as a rise in plasma cardiac troponin T, serum lactate dehydrogenase, and cardiomyocyte apoptosis; this was aggravated by coadministration of SC236 but not SC560. The degree of injury in animals treated with a combination of doxorubicin and SC236 was attenuated by prior administration of the prostacyclin analogue iloprost. These data raise the possibility of protecting the heart during the administration of doxorubicin by prior administration of prostacyclin.


Subject(s)
6-Ketoprostaglandin F1 alpha/analogs & derivatives , Aspirin/pharmacology , Cardiomyopathies/chemically induced , Cyclooxygenase Inhibitors/toxicity , Doxorubicin/toxicity , Heart/drug effects , Isoenzymes/antagonists & inhibitors , Myocardium/pathology , Nitrobenzenes/pharmacology , Pyrazoles/toxicity , Sulfonamides/pharmacology , Sulfonamides/toxicity , 6-Ketoprostaglandin F1 alpha/urine , Animals , Apoptosis/drug effects , Arachidonic Acid/pharmacology , Biomarkers , Cardiomyopathies/metabolism , Cardiomyopathies/prevention & control , Cyclooxygenase 1 , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Doxorubicin/pharmacology , Enzyme Induction/drug effects , Epoprostenol/biosynthesis , Epoprostenol/physiology , Iloprost/therapeutic use , Isoenzymes/biosynthesis , Isoenzymes/genetics , Isoenzymes/physiology , L-Lactate Dehydrogenase/blood , Male , Membrane Proteins , Myocardium/metabolism , Prostaglandin-Endoperoxide Synthases/biosynthesis , Prostaglandin-Endoperoxide Synthases/genetics , Prostaglandin-Endoperoxide Synthases/physiology , Pyrazoles/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Cytoplasmic and Nuclear/metabolism , Thromboxane B2/blood , Transcription Factors/metabolism , Troponin T/blood
3.
J Pain Symptom Manage ; 17(3): 175-80, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10098360

ABSTRACT

The effect of iontophoretic administration of vincristine in the treatment of postherpetic neuralgia (PHN) was investigated in a prospective, double-blind, placebo-controlled trial. Twenty patients with intercostal or lumbar PHN for more than 6 months that was unresponsive to conventional medical therapy were randomized to receive vincristine 0.01% (n = 11) or saline (n = 9), by iontophoresis over 1 hour daily for 20 days. Demographics and median duration of pain were similar in both groups. Pain scores decreased over the treatment period and were significantly lower on day 20 compared to baseline in both groups. Pain relief was described as moderate or greater in 40% of patients with vincristine and 55% of patients with placebo. There was no statistical difference an actual pain scores on day 20 between the two groups. Moderate or greater pain relief was maintained in 30% of patients with vincristine and 33% of patients with placebo at follow-up on day 90. We conclude that iontophoresed vincristine is no better than iontophoresed saline in the treatment of PHN. The maintained improvement in both groups at 3 months follow-up may reflect the natural history of PHN, or might possibly by related to a beneficial effect of iontophoresis.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Herpesviridae Infections/complications , Neuralgia/drug therapy , Neuralgia/etiology , Vincristine/therapeutic use , Aged , Double-Blind Method , Female , Humans , Iontophoresis , Male , Prospective Studies
4.
J Cardiothorac Vasc Anesth ; 12(6): 642-6, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9854660

ABSTRACT

OBJECTIVE: Prophylactic administration of tranexamic acid (TA), an antifibrinolytic agent, decreases bleeding after cardiac surgery with systemic hypothermia (25 degrees C to 29 degrees C). Warmer systemic temperatures during cardiopulmonary bypass (CPB) may reduce bleeding and thus alter the requirement for TA. The effect of three different doses of TA on bleeding after cardiac surgery with mild systemic hypothermia (32 degrees C) is evaluated. DESIGN: Double-blind, prospective, randomized study. SETTING: University hospital. PARTICIPANTS: One hundred fifty adult patients undergoing aortocoronary bypass or valvular cardiac surgery. INTERVENTIONS: Patients received TA, 50 (n = 50), 100 (n = 50), or 150 (n = 50) mg/kg intravenously before CPB with mild systemic hypothermia. MEASUREMENTS AND MAIN RESULTS: Blood loss through chest drains over 6, 12, and 24 hours after surgery and total hemoglobin loss were measured. Autotransfused blood, transfused banked blood and blood products, and coagulation profiles were measured. Analysis of variance on log-transformed data for blood loss and confidence intervals (CIs) of 0.95 were calculated and transformed to milliliters of blood. No patient was re-explored for bleeding. Blood loss at 6 hours was statistically greater in the 50-mg/kg group compared with the other two groups (p = 0.03; p = 0.02). Total hemoglobin loss was statistically greater in the 50-mg/kg group compared with the 150-mg/kg group (p = 0.04). There was no statistical difference in blood tranfusion rate or coagulation profiles among the three groups. However, preoperative hemoglobin level was statistically lower in the 150-mg/kg group compared with the other two groups (p = 0.01). CONCLUSION: Of the three doses of TA studied, the most efficacious and cost-effective dose to reduce bleeding after cardiac surgery with mild hypothermic systemic perfusion is 100 mg/kg.


Subject(s)
Antifibrinolytic Agents/administration & dosage , Blood Loss, Surgical/prevention & control , Cardiac Surgical Procedures , Hypothermia, Induced , Tranexamic Acid/administration & dosage , Adult , Aged , Aged, 80 and over , Blood Coagulation Tests , Blood Transfusion , Cardiopulmonary Bypass , Coronary Artery Bypass , Double-Blind Method , Female , Heart Valves/surgery , Humans , Male , Middle Aged , Prospective Studies
5.
Anesthesiology ; 89(5): 1068-73; discussion 9A, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9821994

ABSTRACT

BACKGROUND: Fast-track cardiac anesthesia, using low-dose narcotics combined with short-acting anesthetic and sedative agents, facilitates early tracheal extubation after cardiac surgery. The incidence of awareness with this anesthetic technique has not been investigated previously. The purpose of this study was to prospectively investigate the incidence of intraoperative awareness with explicit memory of events during fast-track cardiac anesthesia. METHODS: Data were collected prospectively over a 4-month period from 617 consecutive adult patients undergoing cardiac surgery at a university hospital. All patients received a fast-track cardiac anesthetic regimen. Patients underwent a structured interview by a research nurse 18 h after extubation. A standard set of questions was asked during this interview to determine if the patient had explicit memory of any event from induction of anesthesia to recovery of consciousness. RESULTS: Nine patients did not complete a postoperative interview because of death (n = 7) or postoperative confusion (n = 2). The last memory before surgery reported in 420 (69.1%) patients was waiting in the holding area at the operating suite, and in the remaining 188 (30.9%) patients it was lying on the operating table before induction of anesthesia. Two patients (0.3%) had explicit memory of intraoperative events. One of the two patients also had explicit memory of pain. Neither patient reported adverse psychological sequelae. CONCLUSIONS: The authors report an incidence of awareness in fast-track cardiac anesthesia of 0.3%. This is the lowest incidence of awareness currently reported during cardiac surgery. This low incidence of awareness may be related to the use of a balanced anesthetic technique involving the continuous administration of volatile (isoflurane) or intravenous (propofol) anesthetic agents before, during, and after cardiopulmonary bypass.


Subject(s)
Anesthesia , Anesthetics , Cardiac Surgical Procedures , Consciousness/drug effects , Hypnotics and Sedatives , Narcotics , Cardiopulmonary Bypass , Female , Humans , Hypertension/physiopathology , Intraoperative Period , Male , Middle Aged , Prospective Studies
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