Lawrence L. Priano

Differentiation of the cardiovascular effects of CI-581.

1-581 (2(0-chlorophenyl) -2-methylC amino-cyclohexanone) (fig. 1) , which has recently been given the generic name, ketamine, was shown to elevate arterial pressure by McCarthy and associates1 in dogs, and later in man by Domino and cm workers.2 Recently, more complete cardiovascular studies in humans, published by Kreuscher and Gauch3 and Virtue and assoc ia te~ ,~ indicate that the pressor response observed was due to an increased cardiac output. Unfortunately, these authors used only a single dose level of ketamine in their studies. The following work, using three different dose levels of ketamine, was carried out to study cardiovascular parameters, and to gain some insight into the nature of these responses.

Generalized Cardiovascular and Regional Hemodynamic Effects of Meperidine in Conscious Dogs

Changes in both total cardiovascular function and regional hemodynamics associated with large doses of intravenous meperidine were studied in conscious dogs in the absence of other drugs or recent surgery. The animals had previously been surgically prepared by placement of aortic catheters and implantation of chronic indwelling electromagnetic and Doppler ultrasonic flow probes on the aorta and on mesenteric, renal, and iliac arteries. Meperidine, 2 mg/kg, produced mild renal vascular dilation (10% maximum decreases in resistance and 5% increases in blood flow), but did not alter the resistances and flows in the mesenteric or iliac vascular beds. Meperidine, 6 mg/kg, again resulted in renal dilation (maximum 22% decreases in resistance and 18% increase in blood flow). The iliac vasculature also dilated (maximum 39% decreases in resistance and 40% increases in blood flow). However, the mesenteric vasculature constricted (89% increases in resistance and 40% decreases in blood flow). Following 2 mg/kg of meperidine cardiac output and aortic pressure decreased significantly while total peripheral resistance increased significantly. Heart rate remained unchanged. Following 6 mg/kg of meperidine total peripheral resistance and aortic pressure decreased significantly while heart rate increased. Cardiac output increased during the first part of the observation period then subsequently decreased significantly. It is concluded that in unmedicated dogs meperidine has significant effects on total cardiovascular function and on regional blood flow.

Alteration of renal hemodynamics by thiopental, diazepam, and ketamine in conscious dogs.

Renal hemodynamic changes associated with thiopental, diazepam, and ketamine were studied in conscious dogs after previous surgical placement of an aortic catheter and a Doppler ultrasonic flow probe on the left renal artery. Thiopental, 10 mg/kg, changed blood pressure minimally whereas 20 mg/kg significantly decreased blood pressure by 5% to 10%. Renal blood flow initially increased significantly, then returned to control levels after both doses. Renal resistance was not significantly altered by 10 mg/kg of thiopental whereas 20 mg/kg significantly reduced resistance by 10%. Diazepam, 1 and 2 mg/kg, caused transient increases in arterial pressure of approximately 10%. Renal blood flow significantly decreased 5% to 10% from control levels with both doses. Renal resistance did not change with the 1-mg/kg dose of diazepam, but 2 mg/kg of diazepam increased it by 8% to 12%. Ketamine, 2.5 and 5 mg/ kg, elevated arterial pressure 20% to 40%. Renal blood flow increased significantly by 10% to 15% with both doses of ketamine. This effect lasted longer with the larger dose. Renal resistance was significantly elevated by the 2.5-mg/ kg dose of ketamine, whereas 5 mg/kg did not alter this variable. In conclusion, each of these drugs maintains renal blood flow reasonably well in an unanesthetized animal. However, ketamine appears to be more beneficial than thiopental, which in turn, is superior to diazepam in this regard. Little dose-response effect was evident for any of the drugs. Furthermore, it should be noted that changes in arterial pressure can be misleading when perfusion of this vascular bed is considered.

Bartter's syndrome: anesthetic implications based on pathophysiology and treatment.

We recently managed a patient for elective orthopedic surgery (hip fusion due to aseptic necrosis of the femoral head related to a motor vehicle accident) and who had a rare syndrome originally described by Bartter (1). This syndrome consists of renal juxtaglomerular apparatus hyperplasia; elevated plasma renin, angiotensin 11, and aldosterone; hypokalemic, hypochloremic metabolic alkalosis; and decreased vascular reactivity to the pressor actions of angiotensin I1 and norepinephrine (2-7). Characteristically, these patients are normotensive. We were unable to locate literature dealing with the anesthetic management of patients with this syndrome, and so we present this case report, which highlights the problems experienced in management of this case.

Effects of high-dose fentanyl on renal haemodynamics in conscious dogs

The renal haemodyrumic effects of high doses of fentanyl were examined in 17 unanaesthethed, chronically implanted dogs, in order to avoid the confusing effects of superimposed anaesthesia and acute surgical procedures. Ten to fourteen days prior to the study, a Doppler flow probe was positioned around the left renal artery and u Tygon catheter was placed into the lower abdominal aorta through a lumbar arterial side branch. During the experiments, the trained animals were lying quietly on their right side. Following steady-state awake baseline measurements, an intravenous fentanyl infusion, 25µg-kg (lower dose), or50µg.kg (higher dose) was administered over a ten-minute period. Arterial pressure, renal blood flow, calculated renal vascular resistance and arterial blood gases were measured for 20 minutes following the infusion. Observations were made during spontaneous and controlled ventilation, with FIO2 = 0.21 or 1.0. Fentanyl increased arterial pressure 10–40 per cent in all groups and did not, as a rule, significantly affect renal blood flow. Thus renal vascular resistance was increased. There were no significant differences between effects of the 25 µg.kg and the 50 µg- kg doses of fentanyl. It is concluded that these doses of fentanyl, given to the conscious, normovolaemic dog, result in renal vasoconstriction. Renal blood flow does not decrease, however, implying that autoregulation remains intact. These changes are a result of fentanyl, per se, rather than secondary to changes in oxygenation and carbon dioxide levels in the blood and do not appear to have a dose response relationship in the dosage range studied.RésuméOn a exploré les effets causés par de fortes doses de fentanyl chez 17 chiens non-anesthisiés, chroniquement préparés, afin d’Mter les effets incertains de I’anesthisie surajoutée et des opérations aigués. De dix à quatorze jours avant notre expérience, une sonde Doppler a été placée autour de I’artère gauche et un catheter Tygon a été inséré dans I’aorte du bas ventre à trovers la branche lombaire artérielle du cdté, Durant le cours de notre expérience, les animaux d’essais étaient couchés sans bouger sur le côté droit. Après avoir contrôles mesures de base des chiens éveillés, une infusion intraveineuse de fentanyl, 25 igkg (basse dose) et 50 µ-kg1 (dose plus forte) fut administrie pendant une periode de dix minutes. La tension arterielle, le débit san gain rénal, la résistance vasculaire rénale calculée et l’analyse artérielle des gaz du sang ont ’t’ mesurés pendant les vingt minutes suivant I’infusion. On a fait des observations pendant la ventilation spontanée et contrôlée avec le Flo2-0.21 ou 1.0. Le fentanyl augmenta lapression artirielle de 10 äa 40 pour cent chez tous les groupes, mais n’influença pas de manière significative, comme d’usage, le débit sanguin rénal. Done, la résistance vasculaire rénale augmenta. Il n’y a done pas de différences significatives entre la dose de 25 µg-kg’et celle de 50 µg kg’ de fentanyl. Nous concluons done que ces doses de fentanyl administrées aux chiens éveillés et normovolémiques infiuencent la vasoconstriction rénale. Le débit sanguin rénal ne baissa pas mais laisse cependant sous-entendre que l’autorégulation de la circulation rénale reste intacte. Ces changementsésont done produits par le fentanyl même, plutôt que les changements secondaires d’oxyg’nation et de gaz carbonique sanguins et n’apparaissent pas avoir de rapport avec la dose réponse des doses étudiées.

Cerebrospinal fluid levels of endotoxin during endotoxemia.

Summary Dogs were given E. coli endotoxin intravenously to produce the typical hemodynamic and respiratory shock state. Plasma and cerebrospinal fluid levels of endotoxin were measured by the Limulus in vitro endotoxin assay at predetermined intervals for two hours. During the period when the plasma concentration was at its highest, no endotoxin was detected in the cerebrospinal fluid. These results suggest that systemic endotoxin does not produce its effects by acting directly on the central nervous system during the early phase of endotoxemia. The authors appreciate the technical assistance of Nettie Biondo, Dorothy Dillard, and Barbara Turner, and the clerical assistance of Del Traverso. N. C. Trippodo and J. H. Jorgensen were James W. McLaughlin Pre-doctoral Fellows, University of Texas Medical Branch at the time of this research.

Effects of two new dissociative anesthetic agents, ketamine and CL-1848C, on the respiratory response to carbon dioxide.

ITH THE introduction of phencycliw dine, i , z a new concept in anesthetic management arose. Although phencyclidine was never marketed for use in humans, due to its many side-effects, it led to the development of similar drugs that produced fewer adverse effects. One such compound was 2( 0-chlorophenyl) -2(methylamino) cyclohexanone HCl,3 a phencyclidine derivative, which was given the generic name of ketamine (fig. l a ) . The term “dissociative anesthesia” was used to describe the anesthetic state characteristic of both drugs.4 Ketamine acts rapidly, on intravenous or intramuscular administration, to produce a state characterized by catalepsy, analgesia, and amnesia. It is devoid of sedative, hypnotic, or convulsive properties.3 Normal pharyngeal-laryngeal reflexes are maintained,5 skeletal muscle tone remains normal or is increased, and there is mild cardiac stimulation.G

An investigation of possible immunosuppression from ketamine and 100 percent oxygen in normal children.

HE recent advent of human organ alloT transplantation has emphasized to the anesthesiologist, as to most other groups in the United States, the significance of immuno1ogy.l-3 Those centers and anesthesiologists engaged in organ transplantation have been compelled to modify many standard anesthesia practices to accommodate the induced immunosuppression that is a vital part of organ transplantati0n.~-5 In 1970, Humphrey and associates6 suggested that at least in cancer patients an anesthesia-induced immunosuppression may o c m with the use of halothane or halothane-oxygen.

The Direct Effects of Endotoxin on the Heart

Summary The direct effects of gram-negative bacterial endotoxin on the heart were studied, using a Starling heart-lung preparation. The technique was modified so as to have a preparation that was anesthetic free and had a physiologic pH. The data show that endotoxin does not have a depressant action on the heart but that it did delay the onset of cardiac failure in this preparation. Such a phenomenon may be due to a weak supportive action of endotoxin on the heart which can only be detected in the absence of anesthetics, since anesthetics generally depress the heart. A possible explanation for such a phenomenon is offered.

An unusual catheter complication with continuous epidural anesthesia.

Many well-known complications are associated with the use of continuous epidural catheters, including epidural hematomas and abscesses, inadvertent catheter migration into veins or the subarachnoid space, and mechanical problems related to kinking or shearing of catheters. We wish to report an unusual complication that is not mentioned in major texts dealing with regional anesthesia (1-4). This occurred during our use of a Portex epidural catheter. After searching the literature we were able to find only two letters to the editor relating to this type of problem (5-6). Presented here is a report of the incident together with the results of an in vitro laboratory study performed in an attempt to determine why this problem might have occurred.