PubMed Health⌕ Search

Biomedical subjects

J M Murkin

Publications and source records attributed to J M Murkin.

At least 19 recordsLinked to original sources
PubMed1998

A risk-benefit assessment of aprotinin in cardiac surgical procedures.

Aprotinin, a naturally occurring serine protease inhibitor, has found widespread application during cardiac surgical procedures as a consequence of its ability to decrease blood loss and transfusion requirements. While its efficacy in a variety of clinical situations associated with increased risk of blood loss has been well established, at the same time, various complications including anaphylaxis, renal insufficiency, graft closure and arterial thromboses have been reported in association with aprotinin administration. In order to more fully evaluate the risks and benefits associated with aprotinin usage, this review first of all examines the hazards associated with transfusion of blood and blood products. Consideration is then given to various alternatives to allogeneic transfusion, including autologous predonation, acute normovolemic hemodilution, perioperative cell salvage and intraoperative plasma sequestration. A critique of other available pharmacological therapies, specifically desmopressin, aminocaproic acid and tranexamic acid, reviewing their modes of action, efficacy and associated complications, is then made. The role of aprotinin in cardiac surgery is then discussed and its pharmacology, including consideration of its antifibrinolytic, platelet preserving and anti-inflammatory effects is reviewed. Finally, an analysis of potential complications associated with aprotinin administration is undertaken. Issues involving its influence on specific measures of anticoagulation, namely partial thromboplastin time and activated clotting time, and issues relating to graft patency, hypothermic circulatory arrest, renal function, and allergic reactions are analysed and interpreted. In summary, this review concludes that most of the risks associated with aprotinin administration primarily involve inadequate anticoagulation and those of developing an allergic reaction, particularly upon aproptinin re-exposure. The benefits of aproptinin to decrease blood loss and transfusion requirements are confirmed, and there is evidence pointing to the intriguing possibility of a potential salutary effect on perioperative central nervous system complications.

Animals↗
PubMed1997

Cardiopulmonary bypass and the inflammatory response: a role for serine protease inhibitors?

Cardiopulmonary bypass has been shown to activate various inflammatory cascades in the body, resulting in pathophysiological changes that may affect patient outcome after cardiac surgery. Many of these inflammatory cascades are enzyme mediated, involving serine proteases. This report reviews the mechanisms of bypass-mediated activation of the inflammatory cascades and outlines the role of serine protease inhibitors in ameliorating the consequences of the inflammatory response. Experimental data are reviewed on the action of aprotinin in inhibiting the intrinsic coagulation system and in limiting the contact activation of blood platelets and leukocytes. Also reviewed is the role of aprotinin in impacting the incidence of perioperative myocardial ischemia and the central nervous system dysfunction and stroke that are not infrequent complications of surgery with cardiopulmonary bypass.

Aprotinin↗
PubMed1997

Neurologic findings in coronary artery bypass patients: perioperative or preexisting?

OBJECTIVES/DESIGN: This prospective study compares the incidence of preexisting neurologic findings in elective cardiac surgery patients presenting with and without coronary atherosclerosis. SETTING: This single-center study was conducted at a tertiary care hospital. PARTICIPANTS/INTERVENTIONS: After Review Board approval and obtaining written informed consent, 11 patients undergoing valvular heart surgery, 9 patients undergoing similar valvular procedures with concomitant coronary artery bypass surgery, and 4 patients undergoing coronary artery bypass surgery alone were enrolled. Preoperatively, all patients underwent a structured neurologic assessment, and the latter four additionally had preoperative magnetic resonance imaging. MEASUREMENTS AND MAIN RESULTS: The patients, 9 of 24 of whom were female, were aged 46 to 78 years and, other than ischemic heart disease, had medical histories that were similar between groups, with the exception of one patient having scleroderma. None of the patients had a clinical history of neurologic or cerebrovascular disease. Nine percent (1 of 11) of the valve-only patients showed subtle preoperative neurologic abnormalities, compared with 89% (eight of nine) of the valve patients having concomitant coronary surgery and 100% (four of four) of coronary artery bypass-only patients. Additionally, brain imaging scans of all four coronary bypass patients showed nonspecific changes reported as scattered punctate areas of high signal less than 3 to 4 mm in diameter. CONCLUSION: This survey shows that both subtle neurological abnormalities and magnetic resonance imaging lesions can be found in a high percentage of patients with coronary atherosclerosis. Furthermore, this study indicates that without a standardized preoperative neurological examination, postoperative neurologic dysfunction cannot necessarily be ascribed to perioperative events.

Aged↗
PubMed1997

Cognitive dysfunction after ventricular fibrillation during implantable cardiovertor/defibrillator procedures is related to duration of the reperfusion interval.

The insertion of implantable cardioverter/defibrillators (ICD) requires induction of repeated episodes of ventricular fibrillation (VF). The neuropsychological repercussions associated with repeated inducement of hypotension and cerebral ischemia are unknown. In this prospective clinical trial, 1 day prior to ICD assessment/implantation and 5 days postprocedure, 14 patients underwent neurological and cognitive screening. Cognitive dysfunction was defined as impaired performance in one of four cognitive domains. Neurological impairment was defined as a decrement of 2 or more points from baseline of a total possible score of 45 points. Intraoperative hemodynamics, including the reperfusion interval (RI; end of preceding fibrillation to beginning of the next), were recorded. Patients underwent an average of 12 +/- 6 episodes of VF with average duration of mean arterial pressure (MAP) <50 mm Hg for 17 +/- 9 s (range 6-39 s) and of MAP <30 mm Hg for 11 +/- 5 s (range 2-22 s). Nine patients, in none of whom the predetermined criteria for neurologic impairment was met, demonstrated a new subtle neurologic finding postoperatively. Ten of 14 patients met the criterion for cognitive dysfunction 5 days postoperatively. The mean RI between episodes of VF was significantly different between those patients demonstrating cognitive dysfunction and the unimpaired patients (3.1 +/- 0.5 min in the group with cognitive dysfunction vs 3.9 +/- 0.8 min in the unimpaired group, P = 0.027). Five patients without cognitive impairment had longer RI between episodes of circulatory arrest than those showing impaired cognition. We conclude that cognitive dysfunction can occur after insertion of ICD and is related to the duration of RI.

Adult↗
PubMed1996

The effect of temperature management during cardiopulmonary bypass on neurologic and neuropsychologic outcomes in patients undergoing coronary revascularization.

Several studies suggest that normothermic ("warm") bypass techniques may improve myocardial outcomes for patients undergoing cardiac operations. Normothermic temperatures during cardiopulmonary bypass may, however, decrease the brain's tolerance to the ischemic insults that accompany all cardiac procedures. To assess the effect of bypass temperature management strategy on central nervous system outcomes in patients undergoing coronary revascularization, 138 patients were randomly assigned to two treatment groups: (1) hypothermia (n = 70), patients cooled to a temperature less than 28 degrees C during cardiopulmonary bypass, or (2) normothermia (n = 68), patients actively warmed to a temperature of at least 35 degrees C. Patients underwent detailed neurologic examination before the operation, on postoperative days 1 to 3 and 7 to 10, and at approximately 1 month after operation. In addition, a battery of five neuropsychologic tests was administered before operation, on postoperative days 7 to 10, and at the 4- to 6-week follow-up visit. Patients in the normothermic treatment group were older (65 +/- 10 vs 61 +/- 11 years in the hypothermic group), had statistically less likelihood of preexisting cerebrovascular disease, and had higher bypass blood glucose values (276 +/- 100 mg/% vs. 152 +/- 66 mg/% in the hypothermic group). All other patient characteristics and intraoperative variables were similar in the two treatment groups. Seven of 68 patients in the normothermic group were found to have a central neurologic deficit, compared with none of the patients cooled to 28 degrees C (p = 0.006). Performance on at least one neuropsychologic test deteriorated in the immediate postoperative period in more than one half of all patients in both treatment groups but returned to preoperative levels approximately 1 month after the operation in most (85%). This pattern was not related to bypass temperature management strategy. We conclude that active warming during cardiopulmonary bypass to maintain systemic temperatures > or = 35 degrees C increases the risk of perioperative neurologic deficit in patients undergoing elective coronary revascularization.

Age Factors↗
PubMed1996

Neuropsychologic dysfunction after cardiac surgery: what is the problem?

Twenty years ago Aberg published his seminal studies on the neuropsychologic consequences of cardiopulmonary bypass (CPB). Twenty years later, what is the state of current research on the problem of post-CPB neurologic injury, and what different management techniques have been employed to influence this outcome? This article reviews the definition and assessment of postoperative neuropsychologic dysfunction; epidemiologic data and associated risk factors assessing post-CPB neuropsychologic dysfunction are critically appraised.

Brain Diseases↗
PubMed1995

High-dose vecuronium neuromuscular block: a comparison of arrhythmias and onset of block during sufentanil anaesthesia.

This study compared the heamodynamic effects of sufentanil with those observed following concomitant sufentanil and high-dose vecuronium administration to determine whether vecuronium induces bradyarrhythmias. Sixty coronary artery bypass patients were stratified into beta blocker (n = 30) or non-beta blocker (n = 30) groups and following induction with sufentanil (9 +/- 3 micrograms.kg-1) and midazolam (0.07 +/- 0.04 mg.kg-1), received either succinylcholine 1 mg.kg-1 (SxCh), vecuronium 0.3 mg.kg-1 (Vec 0.3), or vecuronium 0.5 mg.kg-1 (Vec 0.5). Using a Holter ECG monitor, bradyarrhythmias were classified as mild (HR 46-50), moderate (HR 40-45) or severe (HR < 40). In the pre-induction period, there were no differences in the incidence of mild, moderate or severe bradyarrhythmias among the SxCh, Vec 0.3 or Vec 0.5 groups, in either the beta blocker or non-beta blocker groups. Following induction, there were similar reductions in mean heart rate and mean arterial pressure in all three muscle relaxant groups in both the beta and the non-beta blocker groups; however, there was no difference in the incidence of mild, moderate or severe bradyarrhythmias among the SxCh, Vec 0.3 or Vec 0.5 groups. The Vec 0.5 beta blocker group had a higher incidence of mild bradyarrhythmias (32 +/- 36%) than the Vec 0.5 non-beta blocker group (2 +/- 3%, P = 0.017). Using EMG recording, the onset time of maximal neuromuscular block for the Vec 0.3 group (108 +/- 17 sec) was longer (P < 0.05) than the SxCh (76 +/- 21 sec) and Vec 0.5 (82 +/- 13 sec) groups, which were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1995

The role of CPB management in neurobehavioral outcomes after cardiac surgery.

Recent developments in techniques for managing cardiopulmonary bypass are outlined with a view toward interventions aimed at decreasing the incidence of perioperative central nervous system dysfunction and overt stroke. Recent reports assessing central nervous system dysfunction after hypothermic and normothermic cardiopulmonary bypass are reviewed and critiqued along with data assessing techniques for cerebral protection during hypothermic circulatory arrest. Controversy surrounding optimal pH management is explored along with a proposal that pH-stat may be most satisfactory to ensure better brain cooling where circulatory arrest is anticipated, whereas alpha-stat may avoid cerebral hyperemia and thus decrease the cerebral embolic load during moderate hypothermic cardiopulmonary bypass. Newer developments in cerebral monitoring techniques are also reviewed.

Cardiac Surgical Procedures↗
PubMed1995

A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery. I. Mortality and cardiovascular morbidity.

UNLABELLED: The impact of perfusion technique and mode of pH management during cardiopulmonary bypass has not been well characterized with respect to postoperative cardiovascular outcome. METHODS: This double-blind, randomized study comparing outcomes after alpha-stat or pH-stat management and pulsatile or nonpulsatile perfusion during moderate hypothermic cardiopulmonary bypass was undertaken in 316 patients undergoing coronary artery bypass operations. RESULTS: Cardiovascular morbidity and mortality were not affected by pH management, and the incidence of stroke (2.5%) did not differ between groups. Overall in-hospital mortality was 2.8%, eight of the nine deaths occurring in the nonpulsatile group (5.1% versus 0.6%; p = 0.018). The incidence of myocardial infarction was 5.7% in the nonpulsatile group and 0.6% in the pulsatile group (p = 0.010), and use of intraaortic balloon pulsation was significantly more common in the nonpulsatile group (7.0% versus 1.9%; p = 0.029). The overall percentage of patients having major complications was also significantly higher in the nonpulsatile group (15.2% versus 5.7%; p = 0.006). Duration of cardiopulmonary bypass, age, and use of nonpulsatile perfusion all correlated significantly with adverse outcome. CONCLUSIONS: Use of pulsatile perfusion during cardiopulmonary bypass was associated with decreased incidences of myocardial infarction, death, and major complications.

Aged↗
PubMed1995

A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery. II. Neurologic and cognitive outcomes.

UNLABELLED: This double-blind, randomized comparison of pulsatile or nonpulsatile perfusion and alpha-stat or pH-stat management during cardiopulmonary bypass was designed to assess postoperative central nervous system outcomes. METHODS: Neurologic and cognitive testing was conducted before the operation and 7 days and 2 months after the operation in 316 patients having coronary artery bypass and in a reference cohort of 40 patients having major vascular and thoracic operations. RESULTS: As detailed in part I of this study, mortality in patients having coronary bypass was 2.8%. The incidence of stroke was 2.5% and did not differ among bypass groups. Mortality was 2.5% for the major surgery cohort. The incidence of cognitive (p = 0.003) and either neurologic or cognitive dysfunction (p = 0.0002) was higher at 7 days for the coronary bypass group than for the major surgery cohort. The incidence of neurologic dysfunction remained higher (p = 0.050) at 2 months in the coronary bypass group. Cognitive dysfunction at 2 months was less prevalent after 90 minutes of cardiopulmonary bypass in patients managed with alpha-stat than with pH-stat strategy (27% versus 44%, p = 0.047). CONCLUSIONS: Postoperative central nervous system dysfunction is more prevalent in patients having coronary bypass than in those having major operations. Pulsatility has no effect on central nervous system outcomes, but alpha-stat management is associated with a decreased incidence of cognitive dysfunction in patients undergoing prolonged cardiopulmonary bypass.

Aged↗
PubMed1995

Aprotinin decreases blood loss in patients undergoing revision or bilateral total hip arthroplasty.

Two recent studies have shown decreased blood loss in patients given aprotinin undergoing primary hip replacement surgery. Because patients undergoing bilateral (bTHA) or revision total hip arthroplasty (rTHA) suffer more blood loss than those undergoing primary THA, we studied consecutive patients undergoing bTHA or rTHA who were randomized to receive either a blinded solution of 3.8 x 10(6) Kallikrein inactivation units (KIU) aprotinin (n = 29) or placebo (n = 24) throughout the surgical procedure. Total blood loss, measured as intraoperative suction losses, weight of sponges, and postoperative volumetric drainage, was compared between groups. Aprotinin patients had significantly less total blood loss 1498 +/- 110 mL (mean +/- SEM) versus 2096 +/- 223 (P = 0.022), and transfused patients in the aprotinin group received fewer packed red blood cells than placebo-treated patients (confidence interval for the difference -1.69, -0.07). In addition, assessment of biochemical markers of hepatic and renal function did not disclose any clinically important differences between groups. Patients were also assessed for development of deep venous thrombosis (DVT) by preoperative and predischarge bilateral lower limb compression ultrasound. None of the aprotinin-treated patients and three placebo-treated patients demonstrated DVT. Unless this trend for decreased DVT with aprotinin can be confirmed, it is questionable whether the slight reduction in blood loss justifies routine use of this expensive drug.

Aged↗
PubMed1995

Cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. CNS Subgroup of McSPI.

Central nervous system (CNS) complications are common after cardiac surgery. Death due to cardiac causes has decreased, but the number of deaths due to CNS injury has increased. As a first stage in the evaluation of its cerebral protection potential, we evaluated the cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. Thirty patients without history of cerebral vascular disease were randomized to two study groups: control group (n = 15) who received sufentanil and vecuronium, or propofol group (n = 15) who received the control anesthetic and propofol infused to maintain electroencephalogram (EEG) burst suppression. Catheters were placed in the radial artery and right jugular bulb for sampling of systemic arterial and jugular bulb venous blood. 133Xe clearance was used to determine cerebral blood flow (CBF) at the start of normothermic bypass, during stable hypothermia, and when rewarmed to 35-37 degrees C nasopharyngeal temperature. Pharmacologic burst suppression with propofol produced a statistically significant reduction in CBF, cerebral oxygen delivery (DO2), and cerebral metabolic rate (CMRO2) at each measurement interval (P < 0..05 vs control). Cerebral arterial venous oxygen difference (C(a-v)O2), and jugular bulb venous oxygen saturation (SJvO2) were not statistically different between groups, indicating maintenance of cerebral metabolic autoregulation (coupling). The reduction in CBF and CMRO2, prominent during the normothermic phases of cardiopulmonary bypass (CPB), indicates a potential for propofol to reduce cerebral exposure to the embolic load during CPB.

Aged↗