J. Perttilä

Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting

Background Alpha2 ‐Adrenergic agonists decrease sympathetic tone with ensuing attenuation of neuroendocrine and hemodynamic responses to anesthesia and surgery. The effects of dexmedetomidine, a highly specific alpha2 ‐adrenergic agonist, on these responses have not been reported in patients undergoing coronary artery bypass grafting. Methods Eighty patients scheduled for elective coronary artery bypass grafting received, in a double‐blind manner, either a saline placebo or a dexmedetomidine infusion, initially 50 ng [center dot] kg‐1 [center dot] min‐1 for 30 min before induction of anesthesia with fentanyl, and then 7 ng [center dot] kg‐1 [center dot] min‐1 until the end of surgery. Filling pressures, blood pressure, and heart rate were controlled by intravenous fluid and by supplemental anesthetics and vasoactive drugs. Results Compared with placebo, dexmedetomidine decreased plasma norepinephrine concentrations by 90%, attenuated the increase of blood pressure during anesthesia (3 vs. 24 mmHg) and surgery (2 vs. 14 mmHg), but increased slightly the need for intravenous fluid challenge (29 vs. 20 patients) and induced more hypotension during cardiopulmonary bypass (9 vs. 0 patients). Dexmedetomidine decreased the incidence of intraoperative (2 vs. 13 patients) and postoperative (5 vs. 16 patients) tachycardia. Dexmedetomidine also decreased the need for additional doses of fentanyl (3.1 vs. 5.4), the increments of enflurane (4.4 vs. 5.6), the need for beta blockers (3 vs. 11 patients), and the incidence of fentanyl‐induced muscle rigidity (15 vs. 33 patients) and postoperative shivering (13 vs. 23 patients). Conclusions Intraoperative intravenous infusion of dexmedetomidine to patients undergoing coronary artery revascularization decreased intraoperative sympathetic tone and attenuated hyperdynamic responses to anesthesia and surgery but increased the propensity toward hypotension.

Effects of dexmedetomidine on coronary hemodynamics and myocardial oxygen balance

Objective: α2-Adrenergic agonists decrease central sympathetic outflow and maintain normal transmural myocardial blood flow distribution, but intravenous bolus doses of these agents can also induce excessive coronary vasoconstriction and myocardial ischemia. The hypothesis of the present study was that a rapid intravenous bolus of dexmedetomidine, a specific α2-adrenergic agonist, will cause coronary vasoconstriction and accompanying myocardial ischemia in young pigs. Design: Prospective, controlled study on experimental animals. Setting: Animal laboratory of a university cardiorespiratory research center. Participants: Twelve domestic 8-week-old open-chest pigs, anesthetized with high-dose fentanyl. Another six pigs served as controls. Interventions: Sequential intravenous dexmedetomidine boluses of 3, 10, and 30 mg/kg were administered, and responses were measured during peak changes (2 minutes after injection) and during recovery after each dose. Measurements and Main Results: Left anterior descending coronary artery blood flow, calculated regional coronary vascular resistance, myocardial extraction of oxygen and lactate, plasma catecholamine levels, and conventional central hemodynamic parameters were measured. The two higher doses of dexmedetomidine induced 21% and 29% immediate increases in left anterior descending coronary artery blood flow. At the same time mean systemic blood pressure and pulmonary capillary wedge pressure increased, and calculated regional coronary vascular resistance increased. Myocardial extraction of oxygen and lactate remained unchanged. Conclusions: Large intravenous doses of dexmedetomidine caused moderate regional coronary vasoconstriction without metabolic signs of myocardial ischemia in young domestic pigs at the same time as a marked vasoconstrictive response in the systemic circulation.

Blood Transfusion with Autologous and Leukocyte-depleted or Standard Allogeneic Red Blood Cells and the Immune Response to Open Heart Surgery

Allogeneic blood transfusions have been associated with impaired outcome in surgical patients. This effect may be mediated by leukocytes. Animal experiments have shown that at least some of the effect can be modified by removal of leukocytes from transfused blood. Therefore, we compared the effects of autologous + leukocyte-depleted against standard allogeneic red blood cell transfusion on postoperative immunosuppression in 24 men undergoing coronary artery bypass surgery. In the autologous + leukocyte-depleted red blood cell transfusion group, patients received 800 +/- 200 mL (mean +/- SD) autologous blood and 2.2 +/- 2.0 units (mean +/- SD) of leukocyte-depleted saline-adenine-glucose-mannitol (SAGM) red blood cells. In the standard red blood cell transfusion group, patients were transfused with 5.5 +/- 1.4 units (mean +/- SD) of SAGM red blood cells. Leukocyte and differential counts; percentages of lymphocyte subpopulations (CD3-, CD4-, CD8-, CD16-, CD20-, CD25-, and B5-positive lymphocytes) and monocytes (CD14); phytohemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and unstimulated proliferation of separated lymphocytes; unstimulated and pokeweed mitogen-stimulated production of IgG, IgM, or IgA; and serum interleukin-6, interleukin-1 beta, and serum C-reactive protein concentrations were measured preoperatively and on postoperative Days 1, 7, and 21. Significant changes were seen in these variables, but there were no differences between the groups. Three of the 12 patients in the allogeneic leukocyte-containing red blood transfusion group became human lymphocyte antigen (HLA) alloimmunized. No infections or other complications occurred in any patients. We conclude that HLA alloimmunization was the only effect that could be modified by use of autologous blood.

Effects of cardiopulmonary bypass on lymphocytes and their subset counts with or without use of autotransfusion devices.

Lymphocytes and their subset counts were determined in 30 cardiac surgery patients during cardiopulmonary bypass (CPB) with or without use of an autotransfusion device. In the autotransfusion group, centrifuged and washed autologous red blood cells (median 400 mL [range 200-770 mL]) and in the control group corresponding amounts of homologous packed red blood cells (median 500 mL [range 250-750 mL]) were transfused after declamping the aorta. The percentages of T lymphocytes (CD3) and T cytotoxic cells (CD8) increased in both groups (CD3 up to 5%, P < 0.05 and CD8 up to 35%, P < 0.01), but the percentage of T helper cells (CD4) did not change. The ratio of CD4/CD8 cells decreased (up to 34%, P < 0.01). The percentage of naive resting T cells (CD45RA) increased slightly (up to 8%, P < 0.05) whereas the percentages of memory T cells (CD45RO), T cells with IL-2 receptor (CD25), and natural killer cells (CD16) remained unaltered. The percentage of HLA-DR positive lymphocytes increased during CPB (up to 18%, P < 0.05), but it was decreased thereafter (up to 16%, P < 0.05). The percentage of monocytes (CD14) decreased first during CPB in both groups (up to 32%, P < 0.01), but it was higher in the autotransfusion device group (decreased 29% from initial value) than in the control group (decreased 65% from initial value) at the end of CPB (P < 0.05). This study shows that extracorporeal circulation has an effect on lymphocytes and their subset counts. The changes were slightly immunosuppressive. By contrast, use of autotransfusion devices had only minor effects.

Lack of modulation of postoperative immunosuppression by isotonic amino acid infusion.

Effects of an isotonic amino acid solution on the immune defence systems of surgical patients were studied. Twenty-two patients admitted for major abdominal operations were randomly allocated into two groups. Eleven of them received 1 liter of 3% amino acid solution daily for 5 days postoperatively, while 11 control patients received balanced 5% glucose-containing electrolyte solutions. Immune variables were studied preoperatively and at 1, 3 to 4, and 6 to 7 days postoperatively. These studies included leukocyte and differential counts, T (OKT3+), B (sIg+), T helper/inducer (OKT4+) and suppressor/cytotoxic (OKT8+) cell determinations, measurement of in vitro lymphocytic responses to phytohemagglutinin (PHA), pokeweed mitogen (PWM) and Staphylococcus aureus Cowan I (StaCw) in cultures of separated lymphocytes, and to PHA, concanavalin A (Con A), and PWM in whole blood cultures. B lymphocyte functions were studied by measuring synthesis of immunoglobulins IgG, IgM, and IgA in the cell culture medium when lymphocytes were stimulated with PWM alone and in the presence of Con A or hydrocortisone. Postoperative amino acid infusion slightly improved the capacity of lymphocytes to synthetize and secrete IgG and IgM. By contrast, no improvement was seen in cell counts or lymphocyte transformation patterns.

Effects of different plasma substitutes on plasma fibronectin concentrations in patients undergoing abdominal surgery

Plasma fibronectin is important for host defences as an opsonin of the mononuclear phagocyte system (MPS). The effects of three types of plasma substitutes, crystalloid, gelatin and dextran solutions, on plasma fibronectin levels were studied in patients undergoing abdominal surgery in relation to serum total protein and serum C‐reactive protein (CRP) levels. Plasma fibronectin levels decreased during induction of anaesthesia and infusion of an electrolyte solution before infusion of the plasma substitute, and they were further decreased during operation after infusion of plasma substitutes and remained depressed on the first postoperative day in all study groups (P<0.05–0.01). In the crystalloid and dextran groups, plasma fibronectin levels exceeded preoperative levels by the 4th‐5th postoperative day (P<0.05–0.01), but in the gelatin solution group they remained depressed (P<0.01). Serum total protein levels remained lower than preoperative values throughout the study period (P<0.05–0.01), whereas CRP levels were many times higher on days 1 and 4–5 postoperatively in all groups (P<0.01).

Phospholipases A2 in the serum of patients after coronary artery bypass surgery.

OBJECTIVE To study the catalytic activity of phospholipase A2 and the concentrations of group I and group II phospholipase A2 in the sera of patients during and after coronary artery bypass surgery. DESIGN Prospective study. SETTING University hospital and research laboratory. PATIENTS Fourteen consecutive patients operated on for ischemic heart disease. INTERVENTIONS The catalytic activity of phospholipase A2 and the serum concentrations of group I and group II phospholipases A2 were measured before, during, and after the operation until the seventh postoperative day. A total of 196 blood samples were taken from 14 patients. MEASUREMENTS AND MAIN RESULTS The catalytic activity of phospholipase A2 and the concentration of group II phospholipase A2 increased in the sera of patients after coronary artery bypass surgery. The concentration of Group I phospholipase A2 did not change. The catalytic activity of phospholipase A2 correlated significantly with group II but not with group I phospholipase A2 values. CONCLUSIONS The increase in the catalytic activity of phospholipase A2 in serum after coronary artery bypass surgery is due to group II phospholipase A2. The present results suggest that group II phospholipase A2 is responsible for the physiologic and pathophysiologic effects of catalytically active phospholipase A2 after coronary artery bypass surgery.

Splanchnic and peripheral tissue perfusion in experimental fat embolism

OBJECTIVE To investigate the acute effects of experimental fat embolism on splanchnic and peripheral perfusion and oxygenation in pigs. DESIGN Randomized, controlled trial. SETTING Animal laboratory. SUBJECTS Eighteen domestic pigs, weighing 25 to 31 kg. INTERVENTIONS The 18 pigs were randomized to either the fat embolism or control groups. Nine anesthetized and mechanically ventilated pigs were intracavally infused with a 10% allogeneic bone marrow suspension at a dose of 100 mg/kg over 5 mins (the fat embolism group); nine control pigs received normal saline in the same volume and speed (control group). MEASUREMENTS AND MAIN RESULTS Mean pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary shunt increased, and PaO2 decreased immediately after the bone marrow suspension infusion. In the fat embolism animals, oxygen delivery decreased, oxygen content difference widened, and total oxygen consumption remained high, indicating enhanced oxygen extraction. Further, superior mesenteric artery blood flow and mesenteric oxygen delivery decreased, while intramucosal pH in the small bowel was stable. Subcutaneous PO2 decreased in both groups, whereas transcutaneous PO2 decreased only in the animals receiving bone marrow suspension. Skin red cell flux showed no significant changes. CONCLUSIONS The present model of fat embolism results in significant impairment in systemic oxygenation. Despite this fact, the intestinal oxygenation remains unaffected probably due to sufficient compensatory mechanisms. Transcutaneous PO2 measurements may provide a useful index for early detection of fat embolism.

Effects of open heart surgery on oral mucous host defence systems

Background: The immune response is affected by anaesthesia and surgery. This study was carried out on the effects of open heart surgery on the oral mucous host defence system, which is part of the common mucosal immune system.

Activity of Natural Killer Cells after Postoperative Amino Acid Infusion

Effects of postoperative infusion of a 3% amino acid solution on natural killer (NK) cell activity were studied in 10 patients undergoing major abdominal surgery. Eight additional patients formed the control group. Preoperative NK cell activity against K562 target cells determined in a short-term 51Cr release assay was similar in patients of both groups. After the operation, in general the patients of both groups showed a decrease in NK cell activity (p less than 0.01) but without differences between the groups. There were no changes in the percentages of Leu-7 positive cells (NK cells) between or within the two groups. However, the number of Leu-7 positive cells in blood was lower in the amino acid than in the control group patients during the postoperative days 3-7 (p less than 0.05 and 0.01). In vitro, the amino acid solution proved to be nontoxic both for effector and target cells and no depression of NK cell activity was observed. A 16-hr preincubation of mononuclear cells with the amino acid solution did not affect NK cell activity. The results suggest that postoperative infusion of an isotonic amino acid solution does not routinely offer any advantages over glucose containing electrolyte solution as to its effects on NK cell activity.