Wen-Shin Liu

Cardiovascular responses to nitrous oxide exposure for two hours in man

Cardiovascular responses to increasing (20, 40, and 60%) concentrations of nitrous oxide or nitrogen in oxygen for 15 minutes as well as responses to 2 hours of exposure to 60% nitrous oxide or nitrogen in oxygen were determined and compared in 30 healthy, supine, untrained volunteers who received no other drugs or medications. No concentration of nitrogen produced a significant change in any cardiovascular variable measured, nor did 20 and 40% N2O. Sixty percent nitrous oxide for 15 minutes significantly increased Paco2. heart rate, stroke volume, cardiac output, mean arterial blood pressure, and central venous pressure. Inhalation of 60% nitrogen also produced no significant change in any cardiovascular variable. In contrast, inhalation of nitrous oxide for 2 hours transiently increased arterial blood pressure (at 15 minutes), heart rate (at 15 and 30 minutes), stroke volume (at 15, 30, and 45 minutes) and decreased systemic vascular resistance (at 15 minutes). Cardiac output significantly increased for the 1 st hour of exposure to 60% nitrous oxide but returned to values similar to control (room air) during the 2nd hour. Prolonged inhalation of nitrous oxide resulted in a constant increase in Paco2 and progressive but mild decreases in arterial pH and calculated base deficit but no change in dead space/tidal volume ratios. These findings demonstrate that nitrous oxide stimulates the cardiovascular system in supine, healthy, untrained volunteers but that the stimulation is transient. The data suggest that early stimulation of the cardiovascular system during nitrous oxide breathing may be related to central nervous system excitation secondary to incomplete anesthesia and/or an increase in Paco2.

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.

Cardiovascular dynamics after large doses of fentanyl and fentanyl plus N2O in the dog.

The effects of large doses of fentanyl (0.05 to 2 mg/kg) and fentanyl plus N2O on cardiovascular dynamics were determined in 10 unpremedicated dogs breathing 100% O2. Using computer analysis of the central aortic pulse-pressure curve, stroke volume (SV), cardiac output, heart rate (HR), peripheral vascular resistance (PVR), and systolic, diastolic, and mean arterial blood pressures (BP) were determined while fentanyl was being given at a rate of 0.3 to 0.44 mg/min. Fentanyl caused a dose-related decrease in HR, which was significant at 0.05 mg/kg. Cardiac output, PVR, and systolic, diastolic, and mean arterial BP were also decreased and SV increased. The latter changes became significant at 0.1 mg/kg for diastolic BP; 0.15 mg/kg for cardiac output and mean BP; 0.25 mg/kg for SV and systolic BP; and at 1.25 mg/kg for peripheral vascular resistance. Addition of N2O after fentanyl did not significantly change any parameter, although SV, cardiac output, and HR were usually increased and PVR decreased.These data demonstrate that, while large doses of fentanyl or fentanyl plus N2O do alter cardiovascular dynamics in dogs, the changes appear to be less profound than these produced by equianalgesic doses of morphine. Our findings suggest that large doses of fentanyl-O2 may be an attractive alternative to morphine-O2 anesthesia in critically ill patients.

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.

Comparison of Sufentanil–N2O and Fentanyl–N2O in Patients Without Cardiac Disease Undergoing General Surgery

Sufentanil (mean total dose 2 μ/kg) was compared with fentanyl (mean total dose 15 μ/kg) as a supplement to 60% N2O anesthesia in 30 adult patients undergoing general surgical procedures. Comparisons were made with respect to stability of hemodynamic variables (heart rate and systolic and diastolic blood pressure), changes in stress hormones (cortisol, antidiuretic hormone, epinephrine, norepinephrine, and dopamine), recovery of alertness and orientation, time to extubation, postoperative analgesia, and measures of respiratory depression (resting end-tidal carbon dioxide tension [PETCO2], CO2 response curve for minute ventilation [δVE/δPETCO2]). Hemodynamic variables remained stable and similar in both groups throughout the study. Plasma hormone levels remained similar to baseline in both groups until 1 h postoperatively when epinephrine levels were significantly elevated in both groups (P < 0.05). Recovery times, including time to extubation, were similar in both groups. Patients given sufentanil had less pain 30 min post-operatively than those given fentanyl, although at 60 min postoperatively pain levels were similar in both groups. Small but significant elevations in resting PETCO2 were seen in both groups postoperatively (P < 0.05), but postoperative δVE/δPETCO2 responses were significantly depressed only in patients receiving fentanyl (P < 0.05). The results of this study demonstrate that sufentanil–N2O anesthesia is as effective as fentanyl–N2O in attenuating the hemodynamic and hormonal responses to the stress of general surgery. Because continuous intraoperative PETCO2 monitoring was not employed in this study, intraoperative hypocapnea cannot be strictly excluded as a possible influence on the postoperative measures of ventilatory drive. However, the results of this study suggest that sufentanil–N2O results in less profound respiratory depression and greater analgesia in the immediate postoperative period after general surgery.

Effects of Ventilatory Techniques during Cardiopulmonary Bypass on Post-bypass and Postoperative Pulmonary Compliance and Shunt

Pulmonary compliance and shunt were evaluated preoperatively, 30 minutes after cardiopulmonary bypass, and two hours postoperatively in 132 calves undergoing open-heart surgery with halothane and oxygen anesthesia. The calves were divided into 11 groups with respect to maintenance of the lungs during bypass. In Group 1 the lungs were collapsed during bypass. In all other groups the lungs were mechanically ventilated, statically inflated, or both, with either pure oxygen or nitrous oxide, 50 per cent, in oxygen. All groups had similar compliance and shunt values before operation and sustained significant decreases in compliance and increases in shunt 30 minutes after bypass. Calves exposed to positive-pressure breathing during bypass had higher shunt and lower compliance values after bypass and postoperatively than those not exposed to mechanical ventilation, irrespective of the inflating gas or presence or absence of any amount of static airway pressure. Animals not ventilated during bypass had compliance and shunt values that were not significantly different from preoperative values, while calves that were ventilated had compliance and shunt values that were still significantly altered two hours postoperatively. These data demonstrate that positive-pressure breathing during bypass decreases pulmonary compliance after bypass and postoperatively and increases intrapulmonary shunt, but that the gas inflating the lungs during bypass does not influence either of these variables. The findings also suggest that static pulmonary inflation during bypass offers no advantage over allowing the lungs to remain collapsed.

Haemodynamic effects of intravenous methadone anaesthesia in dogs

The cardiovascular effects of intravenous anaesthetic doses of methadone were evaluated in 30 mongrel dogs breathing oxygen. One half of the dogs were unpremedicated (group B) and the other half (group A) received atropine 1.5 mg intramuscularly 20 minutes before infusion of methadone. After collection of control cardiovascular data dogs in both groups were given 0.3 mg · kg-1 of methadone intravenously over a ten-minute period and cardiovascular dynamics were again recorded immediately following infusion and 20 minutes later. Following this 0.5 mg · kg-1 of methadone was infused over ten minutes and measurements were obtained as with the 0.3 mg · kg-1 dose. Data were recorded in a similar fashion before and following intravenous infusion of methadone 1.0, 1.5 and 2.0 mg · kg-1 in the same animals, so that after the final infusion each animal had received a total accumulated dose of methadone 5.3 mg · kg-1. Group A dogs had significantly higher heart rates, mean aortic pressures and cardiac output than group B dogs during control conditions and throughout the study. Group A dogs showed no change in any cardiovascular variable measured during or after infusion of methadone 0.3 or 0.5 mg · kg-1. Methadone 1.0, 1.5 and 2.0 mg · kg-1 produced slight (but similar) decreases in mean aortic blood pressure but did not change heart rate, cardiac output, pulmonary capillary wedge pressure, right atrial pressure or pulmonary systemic vascular resistance. In group B dogs methadone 0.5 mg · kg-1 produced modest decreases in heart rate, cardiac output and aortic blood pressure. Infusion of methadone 1.0,1.5 and 2.0 mg · kg-1 (total doses of 1.8, 3.3 and 5.3 mg · kg-1) produced changes similar to those with 0.5 mg · kg-1 of the compound in group B animals with the exception of heart rate, which was further decreased, and pulmonary vascular resistance, which was increased with 1.5 and 2.0 mg · kg-1 infusions.These data demonstrate that intravenous anaesthetic doses of methadone produce only minimal changes in cardiovascular dynamics, most of which can be avoided by prior administration of atropine.RésuméLes effets cardiovasculaire de doses anesthésiques de méthadone (injection de 0.3 à 2 mg · kg-1 jusqu’ à des doses cumulatives de 5.3 mg · kg1-1) pendant ľinhalation ďoxygène ont été évalués chez trente chiens de race commune. La moitié des chiens (groupe B) n’a pas reçu de prémédication et ľautre moitié (groupe A) a reçu atropine (1.5 mg pas la voie intramusculaire) 20 minutes avant la perfusion de méthadone. Après le receuil des paramètres cardiovasculares, les chiens des deux groupes ont reçu méthadone 0.3 mg · kg1-1 par la voie veineuse sur une période de 10 minutes et les mêmes données cardiovasculaires enregistrées de nouveau après perfusion et 20 minutes plus tard. Par la suite, on a perfusé méthadone 0.5 mg · kg-1 sur une période de 10 minutes et les mesures reprises comme on ľavait fait auparavant avec la dose de 0.3 mg · kg-1. De façon identique, les mêmes données furent enregistrées de nouveau avant et après la perfusion veineuse de méthadone 1.0, 1.5 et 2.0 kg · mg-1 ’ chez les mêmes animaux, de sorte qu’après la perfusion finale chaque chien avait reçu une dose cumulative de 5.3 mg · kg-1. Les chiens du groupe A présentaient des fréquences cardiaques, des pressions aortiques et des débits cardiaques plus élevés de façon significative que les chiens du groupe B pendant les conditions de contrôle et pendant toute la durée de ľexpérience. Les chiens du groupe A n’ont pas accusé de changements de paramètres cardiovasculaires lorsqu’on faisait la mesure pendant et après la perfusion de methadone 0.3 à 0.5 mg · kg-1. La méthadone (1.0, 1.5 et 2.0mg · kg-1) a produit de légères baisses de la pression aortique moyenne, mais n’a pas changé la fréquence cardiaque, le débit, la pression capillaire bloquée ou auriculaqire droite ainsi que les résistances vasculaires pulmonaire ou systémique. Chez les chiens du groupe B, la méthadone (0.5 mg é kg-1) a produit de légères diminutions de fréquence, de débit cardiaque et de pression aortique moyenne. La perfusion de 1.0, 1.5 et 2.0 mg · kg-1 de méthadone (doses totales 1.8, 3.3 et 5.3 mg · kg-1) a produit les mêmes modifications que 0.5 mg · kg-1 du médicament chez les animaux du groupe B avec ľexception de la fréquence qui a été plus ralentie et de la résistance vasculaire pulmonaire qui a été augmentée avec des perfusions de 1.5 et 2.0 mg · kg-1. Ces données montrent que des doses anesthésiques de méthadone administrées par la voie veineuse produisent peu de changements de la dynamique cardio vasculaire, et que ces changements peuvent être prévenus pas ľadministration préalable ďatropine. Ces données autorisent à penser que la méthadone intra-veineuse peut être une alternative attrayante à la morphine chez les patients dont la réserve cardiaque est diminuée et mérite qu’on en débute ľévaluation clinique chez ľhomme.

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.

Hemodynamic Effects of Butorphanol-Oxygen Anesthesia in Dogs

The cardiovascular effects of two intravenous rates of butorphanol infusion (0.1 and 0.2 mg/kg/min) were measured in 32 dogs breathing oxygen and nitrous oxide in oxygen. Sixteen dogs were premedicated with atropine and the other 16 were unpremeditated. Of the dogs receiving the higher dose infusion rate, 25% moved with a tail-clamp stimulus whereas 75% moved with the lower doses. Butorphanol produced significant but similar cardiovascular depression with the two rates of infusion irrespective of the presence or absence of atropine medication. Addition of nitrous oxide resulted in further cardiac depression in all groups studied. The data suggest that butorphanol is not an attractive alternative to morphine or fentanyl as a narcotic anesthetic.