Judd K. Lunn

High dose fentanyl anesthesia for coronary artery surgery: plasma fentanyl concentrations and influence of nitrous oxide on cardiovascular responses.

Plasma concentrations of fentanyl achieved during high dose fentanyl (25 to 75 μg/kg)-oxygen anesthesia were measured during and after fentanyl infusion and during and after cardiopulmonary bypass in patients with coronary artery disease. In addition, the cardiovascular effects of addition of nitrous oxide during fentanyl-oxygen were evaluated at two different plasma concentrations of fentanyl. Intravenous fentanyl (18 ± 4 μg/kg) produced unconsciousness and resulted in a mean plasma fentanyl concentration of 34 ± 7 ng/ml. Plasma fentanyl increased to 48 ± 8 ng/ml after 25 μg/kg, remained relatively constant for the remainder of the fentanyl infusion, and decreased slowly after termination of infusion. Plasma fentanyl was further decreased (to approximately 40% of peak values) with initiation of cardiopulmonary bypass but underwent little further change throughout the remainder of bypass or for 1 hour after bypass. Fentanyl (25 μg/kg) produced small decreases in mean arterial, pulmonary artery, and pulmonary capillary wedge pressures, and systemic and pulmonary vascular resistances. Additional fentanyl produced no further change in these variables. Fentanyl did not significantly change heart rate, cardiac output, or right atrial pressure at any time during the study. Addition of nitrous oxide to the inspired mixture of gases produced significant but similar decreases in cardiac output and increases in heart rate and pulmonary and systemic vascular resistances both before operation and after bypass. These data indicate that anesthetic doses of fentanyl result in plasma fentanyl concentrations that decay more slowly than analgesic doses of the compound. In addition, they demonstrate that while high dose fentanyl-oxygen anesthesia does not appreciably alter cardiovascular dynamics, addition of nitrous oxide results in significant cardiovascular depression which is similar with both high (before operation) and low (after bypass) plasma concentrations of fentanyl.

Cardiovascular responses to clamping of the aorta during epidural and general anesthesia.

The cardiovascular responses of aortic cross-clamping and declamping with normal and high ventricular filling pressures were compared during epidural and nitrous oxide-morphine anesthesia in 32 male patients undergoing reconstructive aortic surgery. The patients were divided into four groups. Groups I and II had lumbar epidural blocks with bupivacaine and received nitrous oxide in oxygen to breathe; groups III and IV were anesthetized with morphine (2 mg/ kg) and nitrous oxide. During aortic occlusion groups I and III received Ringers lactate at a rate which maintained mean pulmonary capillary wedge pressure3 to 4 torr above pre-anesthetic values whereas groups II and IV were given Ringers lactate rates which keptsimilar to pre-anesthetic values. Prior to cross-clamping mean arterial blood pressure and systemic vascular resistance were lower in groups I and II than in groups III and IV but cardiac output,and pulmonary vascular resistance were similar in the four groups. Cross-clamping of the aorta produced no significant change in any cardiovascular variable measured in any group. Declamping did not significantly alter any variable in groups I and III but produced moderate hypotension in group IV and severe hypotension in group II as well as significant decreases inin both groups. Our data demonstrate that aortic cross-clamping and release result in little change in cardiovascular dynamics in patients anesthetized with epidural or morphine-nitrous oxide and given balanced salt solutions intravenously in amounts adequate to increase left ventricular filling pressures prior to release of the aortic cross-clamp. Our findings also indicate that hypotension can occur in patients in whom left ventricular filling pressures are maintained at normal levels prior to cross-clamp release, especially in patients given epidural anesthesia.

Cardiovascular responses to nitrous oxide during light, moderate, and deep halothane anesthesia in man

The cardiovascular effects of addition of 20, 40, and then BO percent N2O or nitrogen during controlled ventilation with light (0.8 percent), moderate (1.2 percent), and deep (1.6 percent) halothane-O2 anesthesia were determined in 39 volunteers and compared to results obtained in 18 additional volunteers who received similar concentrations of halothane-O2 anesthesia alone over the same time interval.Halothane resulted in significant and similar reductions in heart rate at all concentrations studied hut produced concentration-related decreases in mean arterial blood pressure, stroke volume, and cardiac output and increases in right atrial pressure. Halothane did not significantly change peripheral resistance at any concentration. Addition of N2O did not change arterial blood pressure or heart rate at any concentration of halothane but produced increases in right atrial pressure in all groups. Peripheral resistance was reduced and stroke volume and cardiac output increased when N2O was added to 0.8 percent halothane. Subjects anesthetized with 1.2 percent halothane showed no significant change in stroke volume or cardiac output with addition of any concentration of N2O, while those anesthetized with 1.6 per cent halothane sustained reductions in stroke volume and cardiac output with 60 percent N2O. Peripheral resistance remained unaltered during addition of N2O to 1.2 percent halothane but significantly increased with 1.6 percent halothane. Addition of nitrogen to halothane produced changes that were similar to those occurring during continued halothane-O2 administration. These data demonstrate that addition of N2O during halothane-O2 anesthesia produces significant changes in cardiovascular dynamics which are variable and dependent upon the concentrations of halothane and N2O employed. Our findings suggest that N2O blocks the reduction of peripheral vascular resistance and increases in cardiac output, stroke volume, and heart rate seen with continued halothane-O2 administration when added to moderate or deep levels of halothane.

Peripheral Vascular versus Direct Cardiac Effects of Calcium

Peripheral vascular and direct cardiac effects of calcium chloride were determined in a new animal model, the unanesthetized calf, before and after replacement of its natural heart (NH) with a pneumatically driven artificial heart (AH). Calcium (5 and 10 mg/kg) significantly increased cardiac output (Q1) and reduced systemic vascular resistance (SVR) before and after AH implantation. Increases in Q1 in AH calves and reductions in SVR in both NH and AH calves were, however, transient, being present 5 minutes but not 15 minutes after both doses of calcium. Increases in Q1 and reductions in SVR were significantly (P<.05) greater after 10 mg/kg than after 5 mg/kg calcium in NH and AH calves. Both doses of calcium produced greater (P<.05) increases of Q1 in NH than in AH animals but similar reductions in SVR. Pulmonary vascular resistance, heart rate and pulmonary arterial and right atrial pressures were not significantly altered by either dose of calcium in NH or AH calves. Mean aortic pressure was influenced by 10 mg/kg calcium only, being transiently reduced in AH calves and increased in NH animals. Pulmonary shunt (Qs/Qt) was increased by both doses of calcium in NH calves but only by 10 mg/kg in AH animals. Correlations of mean change in Qs/Qt with mean change in Qt were high both before (r = .99) and after (r = .97) AH implantation. These data demonstrate that calcium significantly reduces SVR in a dose-related manner as well as exerting a positive inotropic effect on the myocardium.

Neutrophil Chemotaxis During Halothane and Halothane-N2O Anesthesia in Man

Polymorphonuclear neutrophil (PMN) function was evaluated in 21 adult male volunteers anesthetized with 0.8, 1.2, or 1.6% halothane-O2, and halothane-O2 plus 20% N2O and 60% N2O. Variables measured included PMN chemotactic index (CI), PMN random migration (RM), and total leukocyte (WBC) and PMN counts. Halothane significantly (p<0.025) increased WBC and PMN counts and caused a concentration-dependent decrease in PMN CI and RM. Addition of 20% N2O did not change any variable; however, adding 60% N2O increased (p<0.05), PMN CI during 1.2 and 1.6% halothane and RM during 1.6% halothane. Termination of N2O reduced CI back to halothane-O2 levels in those receiving 1.2 and 1.6% of the anesthetic but did not significantly alter any other variable. PMN CI and RM remained decreased and WBC and PMN remained elevated during the first 2 postanesthetic hours. WBC and PMN counts were still significantly (p<0.01) elevated the day after anesthesia in the group receiving 1.6% halothane. All other variables returned to control levels 24 hours after anesthesia. These data demonstrate that halothane produces a concentration-dependent reduction in PMN CI which can be partially reversed with the addition of N2O, and suggest that halothane anesthesia may increase susceptibility to bacterial infection by reducing PMN migration toward invading organisms.

URINE CATECHOLAMINE EXCRETION AFTER LARGE DOSES OF FENTANYL, FENTANYL AND DIAZEPAM AND FENTANYL, DIAZEPAM AND PANCURONIUM

SummaryThe effects of fentanyl (0.5 mg/kg iv), fentanyl with diazepam (1 mg/kg iv) and fentanyl, diazepam and pancuronium (0.1 mg/kg iv) on heart rate (HR), mean arterial blood pressure (BP), cardiac output (Qt), urine flow rate and urine epinephrine and norepinephrine excretion were determined in nine dogs. Fentanyl did not significantly change Qt or BP but did reduce HR and urine flow rate ( P < 0.05). Urine epinephrine and norepinephrine excretion rates were significantly increased by fentanyl ( P < 0.05 ). Diazepam caused no significant further changes in Qt, BF or HR 30 minutes after administration, but urine epinephrine and norepinephrine excretion rates were reduced to control (pre-fentanyl ) levels. Addition of pancuronium after fentanyl and diazepam increased urine flow rate to prefentanyl levels and elevated Qt, BP and HR above controls but produced no significant change in urine epinephrine or norepinephrine excretion. These data suggest that fentanyl increases catecholamine blood levels and imply that the latter may be one mechanism by which cardiovascular dynamics are maintained stable during fentanyl anaesthesia. Our findings also demonstrate that cardiovascular stimulation after pancuronium is not associated with increased urinary catecholamine excretion.RésuméLe Fentanyl à forte dose, associé au Diazepam et au Pancuronium, affecte peu la dynamique cardio-vasculaire et, pour cette raison, cette association a été suggérée chez les grands malades. On ne connaît pas ľinfluence de cette technique sur les taux sanguin et urinaire de catécholamines.Nous avons donc étudié les effets du Fentanyl (0.5 mg/kilo i.v. ), du Fentanyl associé au Diazepam ( 1 mg/kilo i.v. ), et de ľaddition de Pancuronium ( 0.1 mg/kilo i.v. ) aux deux autres, ceci chez neuf chiens. Ľon a également déterminé les variations de la fréquence cardiaque, de la pression artérielle moyenne, et le débit cardiaque.Le Fentanyl n’a pas modifié significativement la pression moyenne, ni le débit cardiaque, mais il a diminué ( p < 0.5 ) la fréquence cardiaque et le débit urinaire. Les taux ďEpinéphrine et de Norépinéphrine urinaires ont été significativement élevés (p < 0.05) par le Fentanyl.Trente minutes après son administration, ľaddition de Diazepam n’avait pas modifié la fréquence, la pression moyenne et le débit cardiaque, mais les taux ďexcrétion urinaire ďEpinéphrine et de Norépinéphrine étaient redescendus aux niveaux observés avant ľadministration de Fentanyl. Enfin, ľaddition de Pancuronium à la suite du Fentanyl et du Diazepam augmentait le débit urinaire aux chiffres observés avant ľadministration de Fentanyl, élevait la pression moyenne, la fréquence et le débit cardiaques, mais n’amenait pas de modification dans ľexcrétion urinaire ďEpinéphrine et de Norépinéphrine.

Cardiovascular stability during carotid endarterectomy: Endotracheal intubation versus laryngeal mask airway

STUDY OBJECTIVE To compare cardiovascular stability during carotid endarterectomy in groups managed either with laryngeal mask airway (LMA) or endotracheal intubation. DESIGN Randomized, retrospective, blinded study. SETTING Teaching hospital. PATIENTS 61 ASA physical status II, III, and IV unpremedicated adult males scheduled for carotid endarterectomy. INTERVENTIONS Following standardized anesthetic technique, including intravenous (i.v.) induction with thiopental sodium 3 to 4 mg/kg, fentanyl 2 to 3 microg/kg), and isoflurane, standard intraoperative cardiovascular monitoring plus direct arterial blood pressure measurements were instituted. Patients were randomly assigned to an endotracheal intubation or LMA group. MEASUREMENTS AND MAIN RESULTS Distinct intraoperative episodes of +/- 25% increase or decrease of mean arterial blood pressure (MABP) and heart rate (HR) when compared with preinduction baseline values, and the number of such episodes requiring interventional therapy were recorded from a blinded anesthesia record retrospectively. Mean end-tidal isoflurane determination and total case duration enabled calculation of minimum alveolar concentration (MAC) hours of isoflurane administered. The LMA group had a significantly (p < 0.05) lower incidence of increased MABP and HR episodes and such episodes requiring drug therapy than did the endotracheal intubation group. No difference was found in the length of surgery, mean end-tidal isoflurane concentration, or the total number of MAC hours of isoflurane administered. CONCLUSIONS During carotid endarterectomy, a reduced incidence of hypertensive and tachycardic episodes, as well as such episodes requiring interventional drug therapy, was found in the group whose airway is managed by LMA when compared with endotracheal intubation.

Cardiovascular and respiratory effects of isoproterenol before and after artificial heart implantation.

Quantitation of peripheral vascular versus direct cardiac effects of isoproterenol (0.002 mg/kg) was attempted in a new pharmacologic animal model, the unanesthetized calf, before and after replacement of its natural heart with a pneumatically driven artificial heart (AH). Isoproterenol significantly increased (p< 0.01) cardiac output and pulmonary shunt and decreased aortic blood pressure before and after AH replacement. Elevation of cardiac output and pulmonary shunt was greater (p< 0.05) and depression of aortic pressure less (p< 0.05) before AH replacement than after. Isoproterenol did not change pulmonary artery (PA) or right atrial (RA) blood pressures before AH implantation but did reduce (p< 0.05) PA diastolic and mean pressures and increase mean RA pressures after. Systemic vascular resistance was significantly (p< 0.01) reduced by isoproterenol before and after AH implantation. Heart rate, O2 uptake, respiratory rate, tidal volume, and minute volume were all markedly increased before AH implantation but unchanged after. These findings demonstrate that approximately half the increase in output and pulmonary shunt and all changes in O2 uptake and respiratory dynamics after administration of isoproterenol are related to cardiac effects of the drug. Our data also suggest that the unanesthetized bovine before and after AH replacement is a unique model for study of the differential pharmacology of drugs with respiratory, cardiac, and peripheral vascular effects.

Cardiovascular Effects of Nitrous Oxide During Meperidine Infusion in the Dog

The cardiovascular effects of a large dose of meperidine (8 mg/kg IV) followed by continued slower infusion of the drug (4 mg/kg/hr) and then addition of increasing concentrations (10 to 70 percent) of N2O or nitrogen during continued meperidine infusion were determined in 18 dogs. Meperidine (8 mg/kg) produced a marked (p<0.01) decrease in stroke volume (SV), cardiac output (&OV0422;T), systemic vascular resistance (SVR), mean arterial blood pressuremean pulmonary artery pressureand also reduced (p<0.05) mean right atrial pressurebut did not significantly change heart rate (HR). During continued meperidine infusion, SV, &OV0422;T, andincreased until they became similar to premeperidine controls, while HR increased so that it was higher (p<0.05) than controls.and SVR also increased during continued meperidine infusion; however, they remained less than control values. Addition of N2O did not significantly change SV orbut produced reductions in HR and &OV0422;T and increases inand SVR when compared to similar concentrations of nitrogen.These data demonstrate that rapid infusions of large doses of meperidine produce marked depression in cardiovascular dynamics which recover when the meperidine infusion is slowed. Addition of Na2O during meperidine infusion results in significant reductions in HR and &OV0422;T and increases inand SVR. Our findings indicate that N2O-meperidine anesthesia tends to preserve systemic blood pressure but at the expense of a reduced &OV0422;T and increased SVR.

Peripheral vascular and direct cardiac effects of digoxin in the calf.

Peripheral vascular and direct cardiac effects of intravenous digoxin (5, 10, and 15 μg/kg) were determined in a pharmacologic animal model, the unanesthetized calf before and after replacement of its natural heart (NH) with a pneumatically driven artificial heart (AH). All doses of digoxin significantly increased cardiac output and stroke volume 30 and 60 minutes after administration before and after AH replacement. Increases in output and stroke volume were greater before AH replacement than after. Increases in output were similar with all doses of digoxin in AH calves but greater with increasing doses in NH calves. Digoxin produced significant and similar increases in systemic vascular resistance within 5 minutes and significant and similar decreases 25 and 55 minutes later in NH and AH calves. While increases in systemic vascular resistance were greater with 10 and 15 μg/kg than with 5 μg/kg of digoxin, decreases in resistance were similar at all doses of digoxin in NH and AH animals. Mean aortic blood pressure transiently increased 5 minutes after all doses of digoxin in NH calves. Heart rate was reduced by all doses of digoxin 5 minutes after administration in NH calves but was unchanged from control in subsequent measurements. Heart rate was fixed in calves with an AH. Mean right a trial pressure was increased similarly by all doses of digoxin in NH and AH calves 30 and 60 minutes following administration. These data indicate that digoxin had significant peripheral vascular (arterial and venous) effects in the healthy calf and suggest that elevations in cardiac output and stroke volume after its use are partially due to both increases in pre-load and to decreases in systemic vascular resistance (after-load).