Raymond C. Roy

Response of cerebral blood flow to changes in carbon dioxide tension during hypothermic cardiopulmonary bypass

Changes in cerebral blood flow (CBF) in response to changes in Pa were measured by intraaortic injection of133Xe in 12 patients during hypothermic (23–30°C) cardiopulmonary bypass. In each patient, CBF was determined at two randomly ordered levels of Paco2 obtained by varying the rate of gas inflow into the pump oxygenator (Group I, n = 6) or by varying the percentage of CO2 added to the gas inflow (Group II, n = 6). Nasopharyngeal temperature, mean arterial pressure, pump-oxygenator flow, and hematocrit were maintained within a narrow range. In group I, a Paco2 (uncorrected for body temperature) of 36± 4 mmHg (mean ± SD) was associated with a CBF of 13 ± 5 ml.100 g−1·min−1, while a Paco2 of 42 ± 4 mmHg was associated with a CBF of 19± 10 ml · 100 g−1·min−1. In group II, a Paco2 of 47 ± 3 mmHg was associated with a CBF of 20± 8 ml. 100 g−1·min−1, and a Paco2 of 53± 3 mmHg was associated with a CBF of 26 ± 9 ml. 100 g−1·min−1. Within group I, the difference in CBF was significant (p < 0.05); within group II, the difference in CBF was significant at the P < 0.002 level. All CBF measurements were lower than those reported for normothermic, unanesthetized subjects of similar age. The response of the cerebral circulation to changes in CO2 tension was well-maintained during hypothermic cardiopulmonary bypass. CBF increased by an average of 1.07 ± 1.19 (SD) ml. 100 g−1·min−1·mmHg−1increase in temperature-uncorrected Paco2 in Group I, and by 1.05 ± 0.54 ml · 100 g−1·min−1· mmHg−1increase in group II.

Response of cerebral blood flow to phenylephrine infusion during hypothermic cardiopulmonary bypass: influence of PaCO2 management.

Twenty-eight adult patients anesthetized with fentanyl, then subjected to hypothermic cardiopulmonary bypass (CPU), were studied to determine the effect of phenylephrine-induced changes in mean arterial pressure (MAP) on cerebral blood flow (CBF). During CPB patients managed at 28° C with either alpha-stat (temperature-un-corrected PaCo2 = 41 ± 4 mmHg) or pH-stat (temperature-uncorrected PaCo2 = 54 ± 8 mmHg) PaCo2 for blood gas maintenance received phenylephrine to increase MAP ≥ 25% (group A, n = 10; group B, n = 6). To correct for a spontaneous, time-related decline in CBF observed during CPB, two additional groups of patients undergoing CPB were cither managed with the alpha-stat or pH-stat approach, but neither group received phenylephrine and MAP remained unchanged in both groups (group C, n = 6; group D, n = 6). For all patients controlled variables (nasopharyngcal temperature, PaCo2, pump flow, and hematocrit) remained unchanged between measurements. Phenylephrine data were corrected based on the data from groups C and D for the effect of diminishing CBF over time during CPB. In patients in group A CBF was unchanged as MAP rose from 56 ± 7 to 84 ± 8 mmHg. In patients in group B CBF increased 41% as MAP rose from 53 ± 8 to 77 ± 9 mmHg (P < 0.001). During hypothermic CPB normocarbia maintained via the alpha-stat approach at a temperature-uncorrected PaCo2, of ∼40 mmHg preserves cerebral autoregulation; pH-stat management (PaCo2 ∼57 mmHg uncorrected for temperature, or 40 mmHg when corrected to 28°C) causes cerebrovascular changes (i.e., impaired autoregulation) similar to those changes produced by hypercarbia in awake, normothermic patients.

Heparin management protocol for cardiopulmonary bypass influences postoperative heparin rebound but not bleeding

A group of 63 adult patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass (CPB) were studied to examine the relationship between heparin doses administered and postoperative bleeding. Patients were randomly assigned either to receive heparin 200 U/kg and additional heparin as needed to reach and maintain an activated clotting time (ACT) greater than 400 s for CPB (group A, n = 30), or to receive heparin 400 U/kg and additional heparin as needed to reach and maintain a whole blood heparin concentration greater than 4.0 U/ml for CPB (group H, n = 33). Groups were compared for the amount of postoperative bleeding, heparin rebound, homologous transfusion requirements, and standard laboratory coagulation tests. In the last 33 patients studied, additional tests of platelet aggregation and plasma levels of beta thromboglobulin (BTG), antithrombin III, and several markers of fibrinolysis were measured and compared by group. The mean heparin dose was 28,000 +/- 4,800 U for group A and 57,000 +/- 10,700 U for group H (P less than 0.05 for group A vs. group H). At 8 and 24 h postoperatively, mediastinal drainage did not differ significantly between groups (mean 24-h drainage +/- SD = 901 +/- 414 ml in group A, 1035 +/- 501 ml in group H), nor did the incidence of transfusion with homologous blood products.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid administration of a narcotic and neuromuscular blocker: a hemodynamic comparison of fentanyl, sufentanil, pancuronium, and vecuronium

High-dose narcotic anesthetic inductions usually avoid circulatory depression bettrthan do other techniques; however, the selection of a narcotic and neuromuscular blocker influences subsequent hemodynamic responses. One hundred-one patients having aortocoronary bypass graft (CABG) surgery were investigated using four combinations of a narcotic and neuromuscular blocker: group FP (fentanyl 50 μg/kg, pancuronium 100 μg/kg); group FV (fentanyl 50 μg/kg, vecuronium 80 μg/kg); group SP (sufentanil 10 μg/kg, pancuronium 100 μg/kg); and group SV (sufentanil 10 μg/kg, vecuronium 80 μg/kg), each combination being administered over 2 minutes. Hemodynamic functions were then monitored for 10 minutes before tracheal intubation. Significant changes included increases in heart rate in the groups receiving pancuronium and decreases in those receiving vecuronium. In all groups mean arterial pressure initially decreased; systemic vascular resistance index decreased significantly in all groups except SV. Cardiac index decreased significantly only in group SV. Circulatory depression requiring treatment with vasopressor or anticholinergic drugs was more common in patients given vecuronium. Cardiac arrhythmia occurred most often in group SP; only in group FP were there no arrhythmias, ischemic changes, or hemodynamic disturbances requiring intervention. Time to onset of neuromuscular blockade did not differ among the four groups, but transient chest wall rigidity occurred significantly more often with sufentanil than with fentanyl. Overall, the fentanyl/pancuronium combination afforded the greatest hemodynamic stability, whereas the sufentanil/vecuronium combination proved least satisfactory because of bradycardia and hypotension, requiring treatment in 35% of group SV patients. Differences in anesthetic premedication, social habits, preoperative medications, narcotic and muscle relaxant doses, and speed of anesthetic drug administration may also influence hemodynamicresponses and may explain differing results reported by others using the same drug combinations.

CHOOSING GENERAL VERSUS REGIONAL ANESTHESIA FOR THE ELDERLY

Although clinical perceptions and theoretic considerations suggest regional anesthesia should be safer than general anesthesia in elderly patients, current studies indicate no difference in outcomes. Regional anesthesia may still prove superior to general anesthesia if the right patient population or right endpoints are identified for comparison. A study of consequence of outcome, comparing the two approaches has created an expansion of the definition of anesthesia-related complications.

CEREBRAL BLOOD FLOW DECREASES WITH TIME WHEREAS CEREBRAL OXYGEN CONSUMPTION REMAINS STABLE DURING HYPOTHERMIC CARDIOPULMONARY BYPASS IN HUMANS

&NA; Recent investigations demonstrate that cerebral blood flow (CBF) progressively declines during hypothermic, nonpulsatile cardiopulmonary bypass (CPB). If CBF declines because of brain cooling, the cerebral metabolic rate for oxygen (CMRo2) should decline in parallel with the reduction in CBF. Therefore we studied the response of CBF, the cerebral arteriovenous oxygen content difference (A ‐ VDcereO2), and CMRo2 as a function of the duration of CPB in humans. To do this, we compared the cerebrovascular response to changes in the Paco2. Because sequential CBF measurements using xenon 133 (133Xe) clearance must be separated by 15‐25 min, we hypothesized that a time‐dependent decline in CBF would accentuate the CBF reduction caused by a decrease in Paco2, but would blunt the CBF increase associated with a rise in Paco2. We measured CBF in 25 patients and calculated the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. Patients were randomly assigned to management within either a lower (32‐48 mm Hg) or higher (50‐71 mm Hg) range of Paco2 uncorrected for temperature. Each patient underwent two randomly ordered sets of measurements, one at a lower Paco2 and the other at a higher Paco2 within the respective ranges. Cerebrovascular responsiveness to changes in Paco2 was calculated as specific reactivity (SR), the change in CBF divided by the change in Paco2, expressed in mL‐100 g−1·min−1·mm Hg−1. In the entire group of 25 subjects, SR was 0.69 ± 0.33 mL·100g−1·min−1·mm Hg−1 (SD) if Paco2 was reduced and 0.10 ± 0.30 mL·100g−1·min−1·mm Hg−1 if Paco2 was increased (P < 0.001). In patients managed within the lower range of Paco2, SR was 0.63 ± 0.31 and 0.21 ± 0.17, respectively, when Paco2 was reduced or increased (P < 0.05), In patients managed within the higher range of Paco2, SR was 0.76 ± 0.38 and −0.01 ± 0.36, respectively, when Paco2 was reduced or increased (P < 0.01). Estimated CMRo2 remained constant within groups from the initial to the repeat measurements. These results confirm a significant time‐dependent decline of CBF during CPB. Moreover, by demonstrating that CMRo2 did not change significantly as Paco2 was altered in either direction, they suggest that the CBF reduction cannot be attributed to progressive brain cooling during stable, hypothermic, nonpulsatile CPB, but must result from an alteration in cerebrovascular resistance.

Negative and Selective Effects of Propofol on Isolated Swine Myocyte Contractile Function in Pacing-induced Congestive Heart Failure

Background Although propofol (2–6 di‐isopropylphenol) is commonly used to induce and maintain anesthesia and sedation for surgery, systematic hypotension and reduced cardiac output can occur in patients with or without intrinsic cardiac disease. The effect of propofol on myocyte contractility after the development of congestive heart failure (CHF) remains unknown. This study tested the hypothesis that propofol would have direct effects on myocyte contractile function in both healthy and CHF cardiac myocyte preparations. Methods Isolated left ventricular (LV) myocyte contractile function (shortening velocity, micro meter/s) was examined in myocytes from five control pigs and in five pigs with pacing‐induced CHF (240 beats/min, for 3 weeks) in the presence of propofol concentrations ranging from 1–6 micro gram/ml. In addition, myocyte contractility in response to beta‐adrenergic receptor stimulation (isoproterenol, 10–50 nM) in the presence of propofol (3 micro gram/ml) was examined. Results Three weeks of pacing caused LV dysfunction consistent with CHF as evidenced by increased LV end‐diastolic diameter (control 3.3 +/‐ 0.1 cm vs. CHF 5.6 +/‐ 0.2 cm; P < 0.05) and reduced LV fractional shortening (control 34 +/‐ 3% vs. CHF 12 +/‐ 2%, P < 0.05). Propofol (6 micro gram/ml) caused a concentration‐dependent negative effect on velocity of shortening from baseline in both control (67 +/‐ 2 micro meter/s vs. 27 +/‐ 3 micro meter/s; P < 0.05) and CHF myocytes (29 +/‐ 1 micro meter/s vs. 15 +/‐ 1 micro meter/s; P < 0.05). Importantly, CHF myocytes were more sensitive than control myocytes to the negative effects of propofol on velocity of shortening at the lower concentration (1 micro gram/ml). beta‐adrenergic responsiveness was reduced by propofol (3 micro gram/ml) in control myocytes only. Conclusions Propofol has a direct and negative effect on basal myocyte contractile processes in the setting of CHF, which is more pronounced than that on healthy myocytes at reduced propofol concentrations.

Myocyte contractile responsiveness after hypothermic, hyperkalemic cardioplegic arrest : disparity between exogenous calcium and β-adrenergic stimulation

Background Acute left ventricular dysfunction is commonly encountered after hypothermic, hyperkalemic cardioplegic arrest (HHCA) and often requires inotropic intervention for successful separation from cardiopulmonary bypass. However, the basic mechanisms involved in depressed left ventricular function and the cellular basis for the differential effects of inotropic drugs after HHCA are unknown. Accordingly, the goal of this study was to determine the effects of calcium (Calcium2+) and beta-adrenergic receptor agonists (beta AR) stimulation on isolated myocyte contractile function after HHCA. Methods Myocytes were isolated from the left ventricle of nine pigs and randomly assigned to one of the following treatment groups: (1) normothermic, control: incubation in oxygenated cell culture media for 2 h at 37 degrees Celsius; and (2) cardioplegia; incubation in 4 degrees Celsius crystalloid cardioplegia for 2 h, followed by rewarming. Steady-state myocyte contractile function was measured after pulse stimulation at baseline, in the presence of extracellular Calcium2+ (3-10 mM), and in the presence of the beta AR agonist isoproterenol (2-100 nM). Myocyte profile surface area was measured for both normothermic myocytes and myocytes after HHCA. In a separate set of experiments, myocyte contractile function also was documented after 2 h of hypoxic conditions with both normothermic incubation and HHCA, in the presence and absence of beta AR stimulation. Results Baseline myocyte contractile function was significantly less in the cardioplegia group compared to control. Extracellular Calcium2+ produced a dose-dependent significant increase in myocyte contractile function in the normothermic control group, whereas increased extracellular Calcium2+ only minimally increased myocyte contractile function in the cardioplegia group. A dose-dependent, significant increase in myocyte contractile function was observed in both groups after beta AR stimulation by isoproterenol; however, myocyte contractile function in the cardioplegia group was decreased compared to the control group. Hypoxia under normothermic conditions significantly reduced myocyte contractile function, myocyte relaxation, and beta-adrenergic responsiveness. Hypoxia in combination with cardioplegic arrest compounded the negative effects on contractile processes but did not further impair beta-adrenergic responsiveness. Myocyte profile surface area was significantly increased after HHCA. Conclusions The minimal improvement in myocyte contractile function after HHCA with increased extracellular Calcium2+ suggests that Calcium2+ depletion is not the primary mechanism for depressed myocyte contractility after HHCA. On the other hand, because beta AR administration improved myocyte contractile function after HHCA, the cellular basis for the effects of beta AR stimulation after HHCA is probably not increased myocyte Calcium2+ but rather alternative mechanisms, such as changes in myofilament sensitivity to Calcium2+. These results also suggest that the abnormalities in left ventricular function after HHCA result from the direct effects of hyperkalemic induced electromechanical uncoupling as well as relative hypoxic conditions.

Electroencephalographic Evidence of Arousal in Dogs from Halothane after Doxapram, Physostigmine, or Naloxone

: The clinical impressions of enhanced arousal from halothane anesthesia and improvement of postanesthesia recovery scores after doxapram, physostigmine, or naloxone have not been verified in laboratory studies based on the effect of these drugs on MAC. With induction of anesthesia, a shift in the amplitude of the EEG from low to high occurs at anesthetic concentrations well below MAC and appears to coincide with the loss of consciousness. The authors examined the effect of arousal agents on the end-tidal halothane concentration required to produce this shifting EEG. In 24 unmedicated dogs, the end-tidal halothane concentration was elevated to 20 per cent above the shift point concentration (from 0.61 +/- 0.03 to 0.73 +/- 0.03 per cent) and maintained at this level for 30 min. Doxapram, 1 mg/kg, iv, and physostigmine, 0.03 mg/kg, iv, converted the EEG from a high amplitude to a low amplitude tracing in 22 +/- 3 s in eight of eight, and 225 +/- 37 s in seven of eight dogs, respectively. The end-tidal halothane concentration required to restore the shifting EEG was elevated above control for 50 +/- 7 min and 109 +/- 7 min, respectively. Naloxone, 0.06 mg/kg, iv, produced an awake EEG in two of eight dogs in 233 +/- 18 s which persisted for 22 +/- 4 min, and a transiently shifting EEG in three of eight dogs between 200 and 240 s. Naloxone 0.006, mg/kv, iv, produced an awake EEG in 80 +/- 8 s in four of four dogs who had previously received doxapram 3 h earlier. In this model doxapram and physostigmine paralleled the clinically observed onset and duration of arousal. The inconstant arousal from halothane anesthesia induced by naloxone was interpreted in terms of an opiate receptor independent action.

Cerebral blood flow does not change following sodium nitroprusside infusion during hypothermic cardiopulmonary bypass

&NA; Changes in cerebral blood flow (CBF) associated with decreases in mean arterial pressure (MAP) produced by sodium nitroprusside (SNP) infusion were measured by intra‐aortic injection of 133Xe in 17 patients during hypothermic cardiopulmonary bypass (CPB). In each patient, CBF was determined at baseline and then again following SNP‐induced reduction of MAP. Two groups were studied. In Group I (n = 9), PaCO2 was maintained near 42 mm Hg uncorrected for nasopharyngeal temperature (NPT). In Group II (n = 8), PaCO2 was maintained near 60 mm Hg, uncorrected for NPT. Nasopharyngeal temperature, MAP, pump oxygenator flow, PaO2, and hematocrit were maintained within a narrow range in each patient during both studies. Since the baseline CBF determinations were conducted at the higher MAP in all subjects, we corrected post‐SNP CBF data for the spontaneous decline that occurs over time during CPB. In Group I, a reduction in MAP from 76 ± 9 mm Hg (mean ± SD) to 50 ± 6 mm Hg was associated with a reduction in CBF from 17 ± 5 to 13 ± 3 ml‐100 g.min‐1 (P < 0.01), a decrease that became statistically insignificant once the time correction factor had been applied (16 ± 4 ml.100 g‐1.min‐1). In Group II, MAP declined from 75 ± 5 mm Hg to 54 ± 5 mm Hg, and CBF declined from 25 ± 10 to 17 ± 7 ml.100 g.min‐1 (P < 0.01), but, again, after time correction, the CBF decline was statistically insignificant (22 ± 8 ml.100g‐1.min‐1). We conclude that SNP infusion is associated with a decrease in CBF during hypothermic nonpulsatile CPB but that the decrease is not significant when corrected for the duration of cardiopulmonary bypass.