Anesthesia for noncardiac surgery in infants with hypoplastic left heart syndrome following hemi-Fontan operation.
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Anastomosis, Surgical↗
Biomedical subjects
C D Kurth
Publications and source records attributed to C D Kurth.
Different cerebral hemodynamic responses following fluid percussion brain injury in the newborn and juvenile pig.
The present study was designed to characterize the influence of early developmental changes on the relationship among systemic arterial pressure, cerebral hemodynamics, and cerebral oxygenation during the first 3 h following percussion brain injury. Anesthetized newborn (1-5 days old) and juvenile (3-4 weeks old) pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Mean arterial blood pressure increased after brain injury in juveniles (68 +/- 4 to 93 +/- 2 mm Hg within 3 min, n = 6), whereas it decreased after injury in newborns (70 +/- 3 to 51 +/- 3 mm Hg within 3 min, n = 6). Fluid percussion brain injury decreased pial artery diameter more in newborns (132 +/- 5 to 110 +/- 5 microns within 10 min, n = 5) than in juveniles (141 +/- 3 to 133 +/- 3 microns within 10 min, n = 5). Pial arterioles constricted to a greater extent than small pial arteries following brain injury in both age groups. Within 30 sec, brain injury produced a transient increase in cerebral hemoglobin O2 saturation (27 +/- 4%, n = 5) that was reversed to a profound decrease in cerebral hemoglobin O2 saturation (45 +/- 2%, n = 5) in the newborn as measured by near infrared spectroscopy. In contrast, brain injury produced modest increases in hemoglobin O2 saturation (10 +/- 1%, n = 5), followed by mild desaturation (4 +/- 1%, n = 5) in juveniles. Additionally, regional cerebral blood flow was reduced within 10 min of injury in both newborn and juvenile pigs and remained depressed for 180 min in newborns. In contrast, cerebral blood flow returned to control values within 180 min in juveniles. These data show that the effects of comparable brain injury level were very different in newborn and juvenile pigs. Further, these data suggest that reductions in cerebral blood flow following brain injury are more dependent on changes in reactivity of arterioles. Finally, these data suggest that the decrease in cerebral oxygenation, an index of metabolism, coupled with reduced cerebral blood flow, could result in profound hypoperfusion after brain injury.
Age Factors↗
Oxygen metabolism during circulatory arrest.
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Adult↗
Cocaine constricts immature cerebral arterioles by a local anesthetic mechanism.
The effect of cocaine on cerebral arterioles was determined in newborn pigs and the mechanism of action was examined in terms of its local anesthetic and sympathomimetic properties. Forty-three newborn piglets were anesthetized, equipped with a closed cranial window, and the diameter of pial arterioles was measured by intravital microscopy. Increasing concentrations of cocaine (10(-7) M to 10(-3) M) applied onto the cortical surface resulted in a dose-dependent decrease in arteriolar diameter. Coadministration with phentolamine, an alpha-adrenoceptor antagonist, did not inhibit the contractile response to cocaine even though phentolamine blocked the constriction to topically applied norepinephrine. In contrast, coadministration of either tetrodotoxin (Na+ channel blocker), charybdotoxin (K+ channel blocker), or quinacrine (phospholipase A2 inhibitor), or pretreatment with indomethacin (cyclooxygenase inhibitor) attenuated vasoconstriction induced by cocaine. Topically applied lidocaine (10(-7) M to 10(-3) M), a local anesthetic without sympathomimetic properties, caused a dose-dependent constriction similar to cocaine, whereas topically applied nomifensine and desipramine (each 10(-7) M to 10(-3) M), inhibitors of dopamine and norepinephrine re-uptake, respectively, did not constrict cerebral arterioles. These results indicate that cocaine constricts cerebral arterioles by its local anesthetic properties rather than its sympathomimetic properties. The mechanism appears to involve an alteration in the flux of Na+ or K+ or prostanoid metabolism.
Anesthetics, Local↗
Near-infrared monitoring of the cerebral circulation.
Near-infrared spectroscopy is a noninvasive bedside technique for monitoring hemoglobin saturation (HbO2%) in brain vasculature. The method linearly relates the optical signal detected from the surface of the head to HbO2%. To do so, the method relies on constant transcranial optical pathlength and light scattering as well as minimal interference by tissues overlying the brain. This study examined these premises. Optical signals from a dual-wavelength, near-infrared spectrometer were correlated with sagittal sinus HbO2% in 7 anesthetized piglets subjected to 7 different physiological conditions: normoxia, moderate and severe hypoxia, hyperoxia, hypocapnia, hypercapnic hyperoxia, and hypotension. These conditions were induced by varying the inspired O2 concentration (7-100%), ventilatory rate (5-35 breaths/min), and blood pressure (phlebotomy 20 ml/kg) to force HbO2% over a wide range (5-93%). To evaluate interference by tissues overlying the brain, correlations were repeated after the scalp and skull were rendered ischemic. Transcranial optical pathlength was measured by phase-modulated spectroscopy. Linear relationships between optical signals and sagittal sinus HbO2% were found with correlation coefficients ranging from -0.89 to -0.99 (p < 0.05) among animals; however, slope and intercept had coefficients of variability of approximately 15 and 333%, respectively. Almost identical linear expressions were observed whether scalp and skull were ischemic or perfused. Transcranial optical pathlength was constant in each animal, but ranged from 10 to 18 cm among animals. The data indicate that the assumptions underlying near infrared spectroscopy are reasonably accurate in a given animal, but that the constants for transcranial optical pathlength and light scattering are not the same in all animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Response of the newborn cerebral circulation to cocaine.
Cocaine abuse by pregnant women is often associated with neurological injury in the newborn. To explore a vascular-related mechanism of injury, we investigated the effect of cocaine on the cerebral circulation in newborn pigs. During normoxic conditions, cocaine administration (1.5 mg/kg i.v.), resulting in peak plasma cocaine levels on the order of 10(-6) M, decreased cerebral blood flow (CBF) by 14%, as measured by the tracer microsphere method. To elicit the mechanisms by which cocaine decreased CBF, closed cranial windows were placed and the diameter of pial arterioles was measured by intravital microscopy while cocaine (10(-6) M) was applied onto the cortical surface. Topically applied cocaine decreased pial arteriolar diameter by 9%. Vasoconstriction induced by topically applied cocaine was blocked by tetrodotoxin (10(-7) M, Na+ channel blocker), whereas phentolamine (10(-5) M, noradrenergic receptor blocker) had no effect on the arteriolar response to cocaine, which suggested that cocaine effected constriction by an anesthetic and not a sympathomimetic mechanism. To evaluate this hypothesis further, cerebral vessels in the right hemibrain were sympathetically denervated while those in the left hemibrain remained innervated. During normoxia, cocaine (1.5 mg/kg i.v.) decreased CBF equally in both hemibrains, confirming the non-sympathomimetic mechanism. During asphyxia, cocaine administration attenuated cerebral hyperemia in both hemibrains, but in innervated more than in denervated, indicating that anesthetic and sympathomimetic vasoconstriction occurred during asphyxia. We conclude that cocaine constricts the immature cerebrovasculature and decreases CBF by an anesthetic mechanism during normoxic conditions and by both sympathomimetic and anesthetic mechanisms during asphyxia.
Animals↗
Pharmacokinetics and effect of cocaine on cerebral blood flow in the newborn.
The present study investigated the effect of cocaine (COC) on cerebral circulation (CBF) and oxidative metabolism (CMRO2) in the newborn piglet and aimed to relate pharmacokinetics of cocaine to cerebrovascular effects. COC decreased CBF and CMRO2 from 75 to 64 and 4.27 to 3.91 ml/min/100 g, respectively, at 4 min with reduced flow to all brain regions (p < 0.05) which returned to baseline by 10 min. COC was rapidly metabolized with a t1/2 of 43 min and peak plasma concentration of 1,172 ng/ml. Norcocaine (NOR) appeared in plasma and CSF within 3 min of cocaine administration and remained elevated for the duration of the study along with COC in the CSF. These data show that the timing of the peak plasma COC level is associated with maximal decreased CBF. Further, the stable elevated level of COC and NOR in the CSF suggests that biotransformation does not occur in the brain. As a result, accumulation of these drugs may occur in the brain with successive COC use and affect the developing CNS in a deleterious manner.
Animals↗
The effect of fentanyl, sufentanil, and alfentanil on cerebral arterioles in piglets.
The effect of fentanyl, sufentanil, and alfentanil on cerebral arterioles was determined in 17 halothane-anesthetized newborn piglets. A closed cranial window was inserted over the parietal cortex, and changes in the luminal diameter of pial arterioles were measured by intravital microscopy as increasing concentrations of opioid (10(-9)-10(-5) M) were suffused over the cortical surface. Each opioid caused a dose-dependent decrease in arteriolar diameter that was attenuated by coadministration of naloxone (10(-5) M). Fentanyl was more potent than either alfentanil or sufentanil. Naloxone alone had no effect at concentrations < or = 10(-5) M, suggesting that endogenous opioids contribute little to resting cerebrovascular tone. These results indicate that fentanyl, sufentanil, and alfentanil produce cerebral vasoconstriction by action at an opioid receptor and that their vasoconstrictive potency appears to differ from their analgesic potency.
Alfentanil↗
Cocaine and its metabolites constrict cerebral arterioles in newborn pigs.
We examined the effect of cocaine and several of its metabolites on cerebral arterioles in newborn pigs and evaluated the sympathomimetic properties of each of the compounds as a vasoactive mechanism. After piglets were equipped with closed cranial windows, compounds were suffused over the brain surface and pial arteriolar diameter (base line, approximately 100 microns) was recorded. Cocaine, cocaethylene, norcocaine, ecogonine, benzoylecgonine and ecgonine methylester each caused a dose-dependent (10(-8) M to 10(-4) M) decrease in pial arteriolar diameter: maximum percent reductions in diameter induced by each compound (10(-4) M) were, respectively, 12 +/- 1, 12 +/- 2, 11 +/- 1, 7 +/- 1, 7 +/- 2 and 5 +/- 1. In analyzing the dose-response curves, cocaethylene was the most potent vasoconstrictor, followed by cocaine, norcocaine and then ecogonine, benzoylecgonine and ecgonine methylester. Cerebral vasoconstriction induced by topically applied norepinephrine was enhanced by cocaine, norcocaine and cocaethylene, but not by the other three metabolites. Topical application of phentolamine failed to block vasoconstriction elicited by cocaine or its metabolites, although it did block vasoconstriction elicited by norepinephrine. These observations indicate that cocaine and its metabolites constrict the immature cerebrovasculature by a non-sympathomimetic mechanism.
Animals↗
Fluctuations in cerebral oxygenation and blood volume during endotracheal suctioning in premature infants.
To investigate the effect that suctioning of the endotracheal tube has on the cerebral circulation, we monitored brain intravascular hemoglobin saturation (tHbo2%), cerebral blood volume (CBV), and arterial hemoglobin saturation (Spo2) during suctioning in 12 infants (24 to 33 weeks of gestational age) with respiratory distress syndrome treated with mechanical ventilation. The tHbo2% and CBV values were monitored over the forebrain by dual-wavelength near-infrared spectroscopy, and Spo2 was monitored by pulse oximetry of a finger. The monitored variables were stable during the baseline period. With suctioning, Spo2 decreased from 94% +/- 1% to 84% +/- 1%, tHbo2% decreased, and CBV increased (p less than 0.05). Desaturation in the arterial and cerebral circulations began within 5 seconds of the onset of suctioning. Arterial reoxygenation began with the onset of reventilation, whereas reoxygenation in the brain was delayed by 15 seconds. The Spo2, tHbo2%, and CBV values returned to baseline within 1 minute of reventilation. Studies were repeated in six of the infants after the fraction of inspired oxygen was increased to attain a baseline Spo2 of 100%. In the preoxygenated infants, tHbo2%, CBV, and Spo2 remained constant during suctioning. These studies confirm that endotracheal suctioning results in transient hypoxemia, and demonstrate that this is reflected in the brain by vasodilation and deoxygenation. These effects are preventable by preoxygenation before suctioning.
Brain↗
Kinetics of cerebral deoxygenation during deep hypothermic circulatory arrest in neonates.
Brain injury associated with neonatal congenital heart operations performed during deep hypothermia and/or total circulatory arrest is often attributed to cerebral hypoxia. We studied the kinetic changes in cerebrovascular hemoglobin O2 saturation (HbO2%) and total hemoglobin concentration (Hbtotal) in 17 neonates undergoing cardiac surgery as they were cooled to 15 degrees C, underwent total circulatory arrest, and were rewarmed. HbO2% and Hbtotal in brain vasculature were monitored noninvasively by near-infrared spectroscopy. Neonates were cooled over 12 min and rewarmed over 15 min while being perfused using cardiopulmonary bypass (CPB). Total circulatory arrest lasted from 20 to 70 min. We found that HbO2% in brain vasculature increased during the initial 8 min of CPB as nasopharyngeal temperature decreased, and then remained constant until circulatory arrest. After the onset of circulatory arrest, cerebrovascular HbO2% decreased curvilinearly for 40 min; no further hemoglobin desaturation was observed from 40 to 70 min of arrest. The changes in cerebrovascular Hbtotal were quite different from those in HbO2%, as Hbtotal decreased during the initial minute of CPB and circulatory arrest and then remained constant until recirculation. Brain intravascular HbO2% and Hbtotal increased within 3 min after the onset of recirculation to prearrest levels, and during rewarming, HbO2% decreased to normothermic baseline values. The results demonstrate that cerebral oxygenation increased during CPB cooling; O2 was consumed by the neonatal brain during the initial 40 min of deep hypothermic circulatory arrest; and cerebral oxygenation was restored on recirculation. These observations may be important in identifying the etiologies of brain injury during neonatal congenital heart surgery.
Brain↗
Cerebrovascular reactivity to adenosine analogues in 0.6-0.7 gestation and near-term fetal sheep.
During acute hypoxia, fetal sheep less than 0.7 gestation increase cerebral blood flow (CBF) relatively less than fetal sheep near term. We hypothesized that cerebrovascular reactivity to a hypoxic vasodilator metabolite such as adenosine might be diminished in immature fetuses. This study examined cerebral vasoreactivity to adenosine analogues in nine sheep fetuses less than 0.7 gestation (90-103 days) and nine near term (129-143 days). Fetuses were equipped in utero with a closed cranial window, and pial arterioles were studied by intravital microscopy. 5'-(N-ethylcarboxamido)-adenosine (NECA; 10(-9)-10(-5) M) and N6-cyclopentyladenosine (CPA; 10(-9)-10(-4) M) each caused a dose-dependent increase in arteriolar diameter that was attenuated in the presence of the adenosine receptor antagonist 8-phenyltheophylline (8-PT; 5 x 10(-6) M). Dose-response curves to the agonists were similar for both age groups. NECA was a more potent vasodilator than CPA, in keeping with their affinity for the A2 receptor. Suffusion of 8-PT alone at less than 10(-5) M had no effect on arteriolar diameter. We conclude that adenosine is able to dilate fetal cerebral arterioles as young as 0.6 gestation by acting at an A2 receptor, although resting tone is not influenced by adenosine. The immature fetal sheep CBF response to hypoxia is not attributable to undeveloped vasoreactivity to adenosine.
Adenosine↗
Cholinergic reactivity of cerebral arteries in the developing fetal and newborn lamb.
Cerebral arteries of newborn pigs and baboons constrict to acetylcholine, suggesting that endothelium-dependent dilator mechanisms may be lacking in immature cerebral arteries. The present study tested this possibility in the immature sheep by examining the response of cerebral arterioles in fetal and newborn sheep to endothelium-dependent dilator, acetylcholine. Pial arteriolar diameter was measured in 9 anaesthetized foetuses in utero (4 preterm, 90-111 days gestation and 5 term, 128-143 days gestation) and in 5 anaesthetized, newborn lambs (14 days) using a closed cranial window with intravital microscopy. Application of acetylcholine to the pial surface induced dose-dependent increase in pial arteriolar diameter in all age groups; EC50 for acetylcholine was 0.10 +/- 0.03, 0.28 +/- 0.08 and 0.26 +/- 0.17 microM for preterm fetal, term fetal, and newborn lambs, respectively. The data demonstrate a sensitive dilator response to acetylcholine in immature fetuses as well as newborn lambs suggesting that cholinergic-mediated release of endothelium-dependent relaxing factor is functional early in gestation. The contractile response to acetylcholine observed in newborn pigs and premature baboons may reflect a species difference rather than maturational lack of endothelium-dependent dilator mechanisms.
Acetylcholine↗
Association of postoperative apnea, airway obstruction, and hypoxemia in former premature infants.
Airway obstruction plays an important role in the pathogenesis of apnea in premature infants who have not previously undergone anesthesia. To determine the role of airway obstruction in postoperative apnea, we studied 74 former premature infants by integrated recordings of nasal airflow, pneumocardiography, and pulse oximetry during the initial 2 h of recovery from inhalational anesthesia. Apnea (greater than 6 s) was classified as central, obstructive, or mixed, wherein mixed apnea consisted of central and obstructive apnea within the same apneic episode. Postoperative apnea was observed in 23 infants, ranging in age from 31-48 weeks postconception: 12 had inguinal herniorrhaphy (hernia group) and 11 had other procedures (other group). Of the 268 apneic episodes in the hernia group, 73% were central, 6% obstructive, and 21% mixed. Infants in the other group had 505 apneic episodes, with a distribution nearly identical to that in the hernia group. Central and mixed apnea occurred in all infants experiencing apnea, except in 1 infant, who had only central apnea, whereas obstructive apnea occurred in only one third of the apneic infants. Arterial hemoglobin desaturation was significantly more frequent at the end of mixed and obstructive apnea than after central apnea (P less than 0.01). In both groups, arterial hemoglobin O2 saturation (SpO2) decreased to less than 80% in approximately 35% of mixed and obstructive apneic episodes, compared to approximately 5% of central apneic episodes. SpO2 remained greater than or equal to 90% in over 80% of central apneic episodes, compared to 40% of mixed and obstructive apneic episodes.(ABSTRACT TRUNCATED AT 250 WORDS)
Airway Obstruction↗
Sympathetic reactivity of cerebral arteries in developing fetal lamb and adult sheep.
The response of cerebral arteries to norepinephrine was examined in vivo in six dated preterm fetal (94-121 days gestation), eight term fetal (127-141 days gestation), five newborn (7-14 days), and five adult sheep, anesthetized and equipped with a closed cranial window. Norepinephrine (10(-8)-10(-4) M in cerebrospinal fluid) caused a dose-dependent decrease in pial arteriolar diameter in fetal and newborn lambs; however, preterm fetuses were 7- and 14-fold more sensitive to norepinephrine than term fetuses and newborn lambs, respectively. The effective concentration of norepinephrine inducing a 15% decrease in diameter (EC15) was 4.6 +/- 1.8, 33 +/- 11, and 64 +/- 23 microM, for the respective ages. Adult cerebral arterioles did not contract to norepinephrine. In preterm and term fetuses, the contractile response to norepinephrine was blocked by alpha 1-antagonist, prazosin (3 mg iv), and was enhanced by cocaine (10(-5) M; EC15 = 0.086 +/- 0.04 and 1.84 +/- 1.20 microM, respectively) indicating that alpha 1-adrenoceptors mediate the response and that the decrease in sensitivity is not caused by development of neuronal uptake processes. In seven fetuses (111-141 days; mean 123 days gestation), electrical stimulation of the superior cervical sympathetic ganglion constricted pial arterioles by 21 +/- 5%; this contractile response was also blocked by prazosin. The cerebral arterioles of the fetus in utero possess a functional sympathetic innervation capable of influencing cerebrovascular resistance. There is a loss of responsiveness of cerebral arterioles to norepinephrine during fetal and postnatal development, suggesting that the contribution of neuroadrenergic mechanisms to cerebrovascular regulation may be relatively unique to the immature brain.
Aging↗
Maturational and anesthetic effects on apneic thresholds in lambs.
Periods of apnea are relatively common in newborns but rare in older infants. Postnatal changes in the response of the central neural respiratory circuits to afferent inputs may have a role in the age-related incidence of apnea. Therefore we determined the central neural apneic threshold to CO2 and superior laryngeal nerve (SLN) stimulation in halothane-anesthetized newborn (4- to 7-day-old) and older (45- to 56-day-old) lambs. The animals were vagotomized, paralyzed, and mechanically ventilated with hyperoxic gas. Phrenic nerve activity served as a monitor of central respiratory output. The CO2 and SLN apneic thresholds were defined as the arterial PCO2 when phrenic activity began after hyperventilation, and the quantity of current applied to the SLN that abolished phrenic activity, respectively. At equivalent concentrations of halothane, newborn lambs had higher CO2 apneic thresholds (P less than 0.05) and lower SLN apneic thresholds (P less than 0.05) than did older lambs. Increasing concentrations of halothane decreased (P less than 0.05) the SLN apneic threshold and increased (P less than 0.05) the CO2 apneic threshold. Equal incremental changes in halothane concentration induced similar changes in the apneic thresholds of both ages of lambs. The data suggest that with maturation, the central neural respiratory circuits become more responsive to CO2 and less responsive to SLN afferents. Halothane alters central neural responsiveness to these inputs in both ages similarly.
Aging↗
Sympathetic regulation of cerebral blood flow during seizures in newborn lambs.
We examined cerebral blood flow (CBF) regulation by the sympathetic nerves in 12 newborn lambs (3-11 days old) during seizures, a potent reflex stimulator of the sympathetic nervous system. CBF was measured with microspheres, and seizures were induced with bicuculline. In six of these lambs, one hemibrain was denervated (D) chronically by interrupting the ipsilateral cervical sympathetic trunk; the other hemibrain remained innervated (I). Before and after 10, 35, and 70 min of seizures, cerebral gray matter blood flow (mean +/- SE ml.min-1.100 g-1) was, respectively, 12 +/- 3 (9%), 71 +/- 12 (21%), 120 +/- 15 (38%), and 54 +/- 5 (14%) greater (P less than 0.05) in the D than in the I hemibrain. In the cerebral white matter, hippocampus, caudate, and thalamus blood flows to the D and I hemibrains were similar before seizures but during seizures they were 10-39% greater (P less than 0.05) in the D than in the I hemibrain. Midbrain, brainstem, and cerebellum D and I blood flows were always similar. In the other six lambs, acute denervation during seizures increased ipsilateral cerebral gray and hippocampus blood flow by 10-31%, but unilateral electrical stimulation decreased ipsilateral cerebral gray, cerebral white, hippocampus, thalamus, and caudate blood flow by 17-27%. The data demonstrate that, during seizures, sympathetic nerve activity modifies regional CBF and the effect is sustained, suggesting a role for the sympathetic nervous system in newborn CBF regulation.
Animals↗
Postoperative apnea in preterm infants.
Preterm infants may become apneic during the immediate post-operative period. To define this risk, the authors studied prospectively the breathing patterns of 47 preterm infants less than 60 weeks postconception with pneumocardiograms before and after general inhalational anesthesia. Eighteen infants (37%) had prolonged apnea (greater than 15 s) postoperatively, and an additional seven infants (14%) had short apnea (6-15 s) postoperatively. An infant's risk of prolonged and short postoperative apnea was related to a young postconceptional age (P less than 0.05) and to a history of necrotizing enterocolitis (P less than 0.01). Furthermore, as the postconceptional age of the infant increased, the risk of postoperative apnea decreased proportionately (P less than 0.025). Among the 18 infants with prolonged apnea, 83% experienced multiple apneic episodes. Manual stimulation was required in order for breathing to return in 13 (72%) of the infants. Breathing resumed spontaneously in four (22%) of the infants, and one infant required mechanical ventilation due to repeated prolonged apnea. The first apneic event occurred within 2 h postoperatively in 13 of the infants (72%); the remaining five infants (28%) had their initial apneic episode as late as 12 h after operation. The postoperative time to the last prolonged apneic event was inversely related to the postconceptional age (P less than 0.01, r = -0.70) and extended up to 48 h postoperatively. The preoperative pneumocardiogram was not a reliable test for predicting postoperative apnea (sensitivity 56%, specificity 83%).(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia, Inhalation↗