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,
* From the Department of Anesthesiology, Advocate Illinois Masonic Medical Center; and
the Departments of Anesthesiology,
Physiology and Biophysics, University of Illinois College of Medicine, Chicago, Illinois, USA.
Address correspondence to: Dr. George J. Crystal, Department of Anesthesiology, Advocate Illinois Masonic Medical Center, 836 West Wellington Avenue, Chicago, Illinois 60657-5193, USA. Phone: 773-296-5375; Fax: 773-296-5362; E-mail: gcrystal{at}uic.edu
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Abstract |
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Methods: Twenty-four dogs were divided into three equal groups: Group I, anesthesia was maintained with ketamine (25 mg·kg–1·hr–1); Group II, with fentanyl and midazolam (F-M; 10 µg·kg–1·hr–1 and 0.5 mg·kg–1·hr–1, respectively); Group III with 1 minimum alveolar concentration (MAC; 1.4%) isoflurane. Radioactive microspheres were used to measure RBF in myocardium, brain, spinal cord, abdominal viscera, skeletal muscle and skin. Cardiac output (CO) was measured by thermodilution and arterial pressure with a catheter situated in the thoracic aorta. Catheters were introduced into the pericardial cavity to infuse isotonic saline and to measure intrapericardial pressure (IPP). Measurements were obtained under control conditions and during tamponade, as defined by an increase in IPP sufficient to reduce mean arterial pressure by 40%.
Results: Tamponade caused decreases in CO and RBF that were comparable under the three anesthetics, except that RBF in subcortical regions of the brain and in the spinal cord were maintained under isoflurane but decreased under ketamine or F-M.
Conclusions: In dogs, intraoperative cardiac tamponade caused comparable changes in RBF under the different anesthetic techniques except that autoregulation was effective in maintaining RBF within the central nervous system only under isoflurane anesthesia. Our findings provide no compelling reason to recommend one anesthetic over the others for maintenance of anesthesia in situations with increased risk for intraoperative cardiac tamponade. However, they cannot be extrapolated to anesthesia induction in the presence of cardiac tamponade.
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Introduction |
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Anesthetic drugs differ in their ability to influence the level of vascular smooth muscle tone and cardiac performance, and the responsiveness of cardiovascular reflex pathways.3,4 Moreover, they have been shown to differentially affect RBF changes during hemorrhagic hypotension.5 However, all previous studies of RBF during tamponade-induced hypotension were performed in conscious dogs or in dogs anesthetized with research drugs, such as pentobarbital.2,6
The most common clinical scenario for cardiac tamponade is its onset in the conscious state followed by surgical treatment under general anesthesia. Ketamine has been recommended for induction of anesthesia in this situation because of its unique cardiovascular stimulant properties.7,8 However, cardiac tamponade can also arise intraoperatively whenever manipulation of the heart or great vessels is involved. This can occur by perforation of the superior vena cava or the right heart by the tip of a central venous catheter9 or during laser-assisted extractions of implanted cardioverter-defibrillator and pacemaker leads, as highlighted in a recent case report.10 Whether one anesthetic technique vs another would afford an advantage in these latter situations is unknown. We tested the hypothesis that the anesthetic technique will influence the changes in RBF during intraoperative cardiac tamponade in a canine model. The findings during ketamine, fentanyl-midazolam, and isoflurane anesthesia were compared.
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Materials and methods |
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After tracheal intubation, the animals were mechanically ventilated with room air supplemented with oxygen. Tidal volume and respiratory rate were established to yield normal values for arterial PCO2 and pH. Arterial blood gases and pH were measured electrometrically (model 413, Instrumentation Laboratories, Lexington, MA, USA), and hematocrit was measured using a micro- centrifuge. Baseline values for arterial PO2, PCO2, pH, and hematocrit were 297 ± 108 mmHg, 35 ± 4 mmHg, 7.40 ± 0.06, and 40 ± 7% (mean ± SD), respectively. Once established, ventilatory parameters were not changed during the course of an experiment. Rectal temperature was monitored and maintained at 38°C with a heating pad. The electrocardiogram (limb lead III) was used for monitoring heart rate.
Polyethylene cannulas were inserted into: 1) the thoracic aorta via the right carotid and right femoral arteries for monitoring arterial blood pressure and to obtain arterial blood samples for gas analysis; and 2) the inferior vena cava via the right femoral vein for iv administration of drugs and fluids. A multiport catheter with a thermistor was introduced into the pulmonary artery using pressure guidance. This catheter was used to obtain measurements of pulmonary capillary wedge pressure and of CO by thermodilution.
After a left thoracotomy in the fourth intercostal space, two polyethylene cannulas were inserted into the pericardial cavity and secured by purse-string sutures. One cannula was connected to a pump so that body temperature isotonic saline could be infused into the pericardial cavity, while the other was connected to a pressure transducer to measure IPP. A thin polyethylene cannula was inserted into the left atrium via a pulmonary vein for injecting radioactive microspheres.
Pressures were measured with a Statham transducers (model P23ID, Gould, Cleveland, OH, USA) and averaged electronically. Blood pressures and heart rate were recorded with a Gould recorder (model 2800S, Gould, Cleveland, OH, USA).
Measurement of RBF
RBF was measured with 15 ± 3 µm microspheres, labelled with gamma-emitting radionuclides, 46Sc, 85Sr, 113Sn, as previously described.6 Approximately 1 x 106 microspheres were administered for each flow determination. The order of the radionuclides was randomized. The microspheres were flushed into the left atrium over 30 sec with 5-mL body temperature, isotonic saline. Administration of the microspheres had no detectable effect on arterial blood pressure or heart rate. Beginning simultaneously with each microsphere injection, arterial reference blood samples were collected at a rate of 6 mL x min–1 for three minutes.
After the final injection of microspheres, the heart was stopped by an iv injection of KCl, excised, trimmed of adipose tissue, valves, and great vessels, and then frozen to facilitate transmural sampling. Full thickness myocardial samples were obtained from the left ventricular and right ventricular free walls and the interventricular septum. The left ventricular and septal samples were cut into thirds transmurally, and the right ventricular samples were cut into halves transmurally to yield regional sections. Samples were also obtained from the brain (cerebral cortex, cerebellum, pons, and medulla), spinal cord, abdominal viscera (kidney cortex, liver, duodenum, pancreas, spleen), skeletal (temporalis) muscle, and skin. Each tissue sample was transferred to a tared counting tube. The tissue and the reference blood samples were weighed and analyzed for radioactivity with a gamma scintillation counter equipped with a multichannel analyzer (model 1282-002, LKB, Turku, Finland). Isotope separation was accomplished by standard techniques for gamma spectroscopy. Values for RBF (in mL x min–1 x 100 g–1) were calculated from the equation:
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where ABF is the rate of arterial reference sampling (mL·min–1), MC is microsphere radioactivity (counts x min–1 x g–1) in the tissue samples, and AC is the total microsphere radioactivity (counts·min–1) in the arterial reference samples. Sufficient counts were accumulated in all samples to maintain counting errors < 3%.
The values for RBF within the left and right ventricular free walls and interventricular septum were averaged to yield estimates for mean transmural myocardial blood flow in each of these structures.
Experimental protocol
The dog was permitted to stabilize for at least 30 min following surgical preparation before baseline measurements for RBF and systemic hemodynamic variables were obtained. This usually occurred at least two hours after the initial administration of the anesthetic. Then pericardial volume and pressure were increased sufficiently to cause a reduction in mean aortic pressure of 40%. This was accomplished by infusing body-temperature, isotonic saline into the pericardial cavity at a rate of 15 mL·min–1. The total volume of saline infused averaged 256 ± 75 mL, and did not differ among the treatment groups. Tamponade measurements were obtained after mean arterial pressure was stable at the reduced level for ten minutes. Then the saline was completely removed from the pericardial cavity, which returned pericardial pressure to zero. After sufficient time for recovery from effects of tamponade (at least 30 min), additional measurements of RBF and hemodynamic variables were obtained.
Statistical analyses
The Student’s t test was used for paired samples to compare control and tamponade conditions.14 Differences among the three treatment groups were assessed using an analysis of variance in conjunction with the Student-Newman-Keuls test.14 A P < 0.05 was considered statistically significant throughout the study.
Results
Control (pre-tamponade) values for systemic hemodynamic variables (Table I available as Additional Material at www.cja-jca.org) and RBF (Tables II and III available as Additional Material at www.cja-jca.org; Figure 1
) were similar for the three experimental groups, with two exceptions. First, heart rate was higher in the ketamine group compared to the fentanyl-midazolam and isoflurane groups. Second, RBF in the cerebral cortex and skeletal muscle was higher in the ketamine group compared to the fentanyl-midazolam and isoflurane groups. Although RBF in the cerebellum, pons, and medulla tended to be higher under ketamine, these differences did not achieve statistical significance.
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Tamponade caused pronounced decreases in myocardial blood flow that were comparable under the three anesthetics (Table II available as Additional Material at www.cja-jca.org; Figure 1
). These decreases in myocardial blood flow demonstrated regional (left and right ventricles and septum) and transmural uniformity; the latter was reflected by values for the endo/epi flow ratio that remained near unity.
On a percentage basis, the tamponade-induced decreases in RBF in the cerebral cortex were similar under the three anesthetics (Table III available as Additional Material at www.cja-jca.org; Figure 1). However, RBF was maintained in the subcortical regions of the brain and in the spinal cord only under isoflurane (Table III available as Additional Material at www.cja-jca.org; Figure 2); it declined in these regions of the central nervous system under ketamine or fentanyl-midazolam.
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). In many tissues, e.g., spleen, pancreas, skeletal muscle, and skin, the decreases in RBF were disproportionate to the decreases in aortic pressure, implying increases in vascular resistance. |
Discussion |
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Baseline effects of anesthetics
In a previous study, we evaluated the variation in RBF in conscious dogs using the microsphere technique.15 The measurements were obtained in the same tissues as in the present study, with the exception that none were obtained in skin or skeletal muscle. These data, presented in Table IV (available as Additional Material at www.cja-jca.org), provide a reference to assess how each anesthetic technique affected the control values for RBF.
A rigorous analysis of direct coronary vasomotor effects of a drug requires knowing the degree of mismatch between coronary blood flow (oxygen supply) and myocardial oxygen demand, as indicated from measurements of coronary venous PO2 or hemoglobin saturation.6 Since these measurements were not available in the present study, we can only speculate on the direct effects of the various anesthetics on the coronary circulation. Notwithstanding differences in myocardial oxygen consumption, the similar values for myocardial blood flow in the anesthetized and conscious animals (Table II vs IV available as Additional Material at www.cja-jca.org) suggest that all the anesthetics had small direct coronary vasomotor effects, if any. This is consistent with previous studies that assessed the direct coronary vasomotor effects of ketamine, fentanyl, and midazolam.16–18 Other studies demonstrated that isoflurane can have a potent, initial coronary vasodilating effect.19 However, this effect was shown to wane over time reflecting adaptation of vascular smooth muscle to the relaxing action of isoflurane.19 In the present study, the approximately two-hour interval between initiating administration of isoflurane and obtaining baseline measurements of RBF provided ample time for appreciable recovery of coronary vasomotor tone.
In keeping with previous reports,20 ketamine caused pronounced increases in blood flow in the cerebral cortex. These responses have been attributed to metabolic vasodilating mechanisms secondary to an increase in cerebral activity and oxygen consumption,20 combined with a direct vasodilating effect.21 Our findings are also consistent with previous studies demonstrating that fentanyl and midazolam can reduce cerebral blood flow, as well as cerebral oxygen consumption.22,23 However, they are in apparent conflict with those indicating that isoflurane can cause marked cerebral hyperemia.24 This may be explained by the ability of the cerebral circulation, like the coronary circulation, to adapt to the vasorelaxing effects of isoflurane.24
All three anesthetics caused decreases in blood flow to the duodenum and pancreas, probably due to a baroreceptor-mediated activation of the sympathetic vasoconstrictor nerves, secondary to reduced arterial pressure and CO.
Hepatic artery flow increased during either ketamine or isoflurane anesthesia, but not during fentanyl anesthesia. This could reflect a direct dilator effect of ketamine and isoflurane on the hepatic artery vascular bed and/or a more preserved ability of the liver to increase hepatic artery flow in the presence of reduced portal flow with these anesthetics. The lack of change in renal blood flow during general anesthesia is consistent with previous studies.5,15
Ketamine produced higher skeletal muscle blood flow values than did fentanyl-midazolam or isoflurane. In the absence of values for skeletal muscle flow in the conscious state, it is not possible to determine with certainty whether these results are because ketamine is a vasodilator or the other anesthetics are vasoconstrictors in the muscle circulation.
Responses during cardiac tamponade
The basic hemodynamic abnormality caused by cardiac tamponade is reduced CO leading to reduced arterial pressure. In the present study, the tamponade-induced reductions in arterial pressure required disproportionate reductions in CO, thus implying increases in systemic vascular resistance, i.e., vasoconstriction. The primary mechanism for this vasoconstriction was likely a baroreceptor-mediated release of norepinephrine from sympathetic nerve terminals, although the renin-angiotensin system may have also played a role.25 An activation of the sympathetic nervous system during tamponade is consistent with the increases in heart rate in all groups. The intrapericardial volume and pressure required to decrease aortic pressure to the predetermined level did not differ among the experimental groups. This implies that the cardiovascular compensatory mechanisms were equally preserved under the various anesthetics.
Decreases in regional myocardial blood flow are a well known consequence of cardiac tamponade.6 In the present study, these responses were comparable with ketamine, fentanyl-midazolam, and isoflurane anesthesia. Previous investigations have provided evidence suggesting that the tamponade-induced decreases in regional myocardial blood flow need not be the result of reduced coronary perfusion pressure and extravascular compression of coronary blood vessels, but can be an appropriate metabolic vascular adjustment to a decreased cardiac work demand due to reduced wall tension (secondary to reduced ventricular pressure and chamber radius).6 These findings include an unaltered myocardial oxygen extraction, continued and undiminished myocardial uptake of lactate (indicating no aerobic metabolism), and an existent coronary vasodilator reserve. In the present study, a uniform transmural myocardial blood flow during tamponade and a recovery of cardiac function, e.g., CO, following reversal of tamponade, were consistent with absence of tamponade-induced myocardial ischemia. The present study provides no evidence that coronary vasomotor control was differentially altered by the anesthetic drugs.
Autoregulation is an intrinsic mechanism by which vascular beds maintain constant blood flow (and oxygen delivery) in the face of changes in blood pressure. In the presence of hypotension, this is accomplished by reductions in vascular resistance secondary to vascular relaxation. Although autoregulation would be operative in most peripheral vascular beds during cardiac tamponade, its influence would be expected to be most prominent in the cerebral circulation, which is not under significant neural or humoral factor compared to the other regions of the body, e.g., abdominal viscera. Our findings indicated that autoregulation was incapable of maintaining RBF within the brain and spinal cord during tamponade-induced hypotension under all three anesthetics, with the exception that it maintained RBF in the subcortical regions under isoflurane. A mechanism to explain this superior regional cerebral autoregulatory capability under isoflurane is uncertain. It should be kept in mind that the tamponade-induced decreases in RBF within the central nervous system would likely not result in impaired function or metabolism given the favourable relationship between oxygen supply (blood flow) and oxygen consumption, i.e., the available oxygen extraction reserve, evident in cerebral tissue.26
Tamponade caused reductions in RBF in the abdominal viscera, skeletal muscle and skin, which did not differ substantively among the three groups. In most of these tissues, the decreases in RBF were disproportionate to the decreases in aortic pressure, implying increases in regional vascular resistance most likely due to baroreceptor-mediated sympathetic vasoconstriction.
Our canine model of experimental cardiac tamponade is well established and validated.6 Slow intrapericardial infusions of saline were used to provide opportunity for activation of compensatory reflex pathways. We found that the removal of saline from the pericardial space reversed the tamponade-induced changes in systemic hemodynamic variables and RBF. This ruled out the possibility that deterioration of the preparation contributed to the findings during tamponade.
Several limitations of these studies warrant address. First, the studies were carried out under positive pressure ventilation. This mode of artificial ventilation has been demonstrated to exacerbate the decreases in CO and arterial pressure during cardiac tamponade.27 The impact of this factor should be the same in all groups. Second, only one dose of each anesthetic was investigated. These doses were obtained from previous studies and they were demonstrated to be adequate based on standard hemodynamic end-points. Although the doses of each anesthetic could be considered moderate and clinically relevant, we cannot claim that the animals of all groups were anesthetized to an identical depth. Third, cardiac tamponade is a continuous variable, and the present results may only apply to the specific severity of this condition studied.
In conclusion, the present findings demonstrated no important differences in the regional hemodynamic effects of cardiac tamponade under the three anesthetic techniques. Thus, they provide no compelling reason to recommend one technique over the others for maintenance of anesthesia in situations with increased risk for cardiac tamponade, such as laser-assisted intracardiac lead extraction, complex electro-physiological procedures, or cardiac catherization.9,10
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Acknowledgments |
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Footnotes |
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This work was presented in part at the Annual Meeting of the American Society of Anesthesiologists, San Francisco, California, October 11–15, 2003.
Accepted for publication April 8, 2004. Revision accepted August 2, 2004.
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References |
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2 Bernath GA, Cogswell TL, Hoffman RG, Klopfenstein HS. Influences on the distribution of blood flow during cardiac tamponade in the conscious dog. Circ Res 1987; 60: 72–81.
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7 Brown DV, O’Connor CJ, Tuman KJ. Emergency situations. In: Estafanous FG, Barash PG, Reves JG (Eds). Cardiac Anesthesia. Principles and Clinical Practice, 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2001: 857–92.
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