1540 SECTION XIV Pediatric Critical Care Anesthesia Principles in the Pediatric Intensive Care Unit C B F (m L/ 10 0 g/ m in ) Pressure (torr) 25 75 125 175 125 PaO2 PaCO2 BP 75 25 • Fig 128 7 Change[.]
1540 S E C T I O N X I V Pediatric Critical Care: Anesthesia Principles in the Pediatric Intensive Care Unit 125 PaCO2 CBF (mL/100 g/min) PaO2 75 25 BP 25 75 125 175 Pressure (torr) • Fig 128.7 Changes in cerebral blood flow (CBF) relative to alterations in arterial partial pressure of car- bon dioxide (Paco2), arterial partial pressure of oxygen (Pao2), and blood pressure (From Shapiro HM Intracranial hypertension: therapeutic and anesthetic considerations Anesthesiology 1975;43[4]: 445–471.) High dose CBF (mL/100 g/min) Moderate dose Low dose Conscious 50 150 BP (torr) • Fig 128.8 Effect of volatile anesthetic on cerebral autoregulation and cerebral blood flow. Both upper and lower limits are shifted leftward relative to conscious autoregulation BP, Blood pressure; CBF, cerebral blood flow (From Drummond K, Shapiro HM, Cerebral physiology In: Miller R, ed Anesthesia 3rd ed Churchill Livingstone: New York; 1990.) velocity, and regional brain oxygenation.46 In contrast to the uncoupling of CBF and metabolic rate demonstrated by volatile agents, dexmedetomidine was found to preserve CBF-CMR coupling due to a more significant decrease in cerebral metabolism compared with blood flow velocity.47 The effects of multiple anesthetic agents on CBF and CMRO2 are depicted in Fig 128.9 Anesthetic agents have variable effects on other neurologic effects, such as emergence delirium Sevoflurane is associated with a high incidence of emergence delirium.10 Significant differences were found in frontal lobe functional connectivity between children with and without emergence delirium after discontinuation of sevoflurane Furthermore, electroencephalographic (EEG) patterns in children without emergence delirium transitioned from an indeterminate state to classifiable sleep before peaceful awakening, whereas patients with emergence delirium demonstrated EEG changes during that indeterminate state.48 Sevoflurane has also been associated with epileptiform activity in pediatric patients with or without preexisting seizure disorders.34,49 Concerns have also been raised regarding anesthetic agents and their toxic neurocognitive effects on the developing brain Animal studies have demonstrated objective findings with respect to an increase in apoptosis in cortical and subcortical tissue, decreases in dendritic spine formation, decreases in synapses, and alterations in neurogenesis with respect to proliferation of neuronal precursor cells, their differentiation into neuron glia, and their migration and functional integration into the neuronal circuitry.50–65 Various anesthetic agents have been demonstrated to produce these findings when used either as single agents or in combination Animal studies have shown an age window of vulnerability that appears to be species specific Dose and duration of exposure have also been associated with these neurocognitive impairments Of note, in some animal studies, the neurotoxic effect can be reversed when the animals are placed in an enriched environment, suggesting that this neurocognitive impairment can be attenuated Recent animal studies have alluded to the possible neuroprotective effects of dexmedetomidine.61,66–68 In a study examining the brains of sheep that underwent surgery at 118 to 120 days’ gestational age with 1.5% to 2.0% isoflurane for to hours and a subsequent 6-hour procedure weeks later, concurrent dexmedetomidine administration revealed decreased hippocampal neuroapoptosis compared with the isoflurane-only group.69 Furthermore, dexmedetomidine mitigated sevoflurane-induced cell cycle arrest and inhibitory factors in neonatal rat hippocampal cells.70 A systematic review of 20 animal studies evaluating neuroprotective and neurobehavioral effects of dexmedetomidine 1541 CHAPTER 128 Anesthesia Effects on Organ Systems CMR CBF CMR CBF –100 –50 50 100 150 –80 –60 –40 –20 Dexmedetomidine 200 20 40 1.2 ng*mL–1 0.15 mg*kg–1*min–1 Ketamine Xenon Desflurane Midazolam 0.15 mg*kg–1 Diazepam 0.20 mg*kg–1 Remifentanil Sevoflurane 0.20 µg*kg–1*min–1 Sufentanil 10 µg*kg–1 Fentanyl 17 µg*kg–1 50% N2O Morphine mg*kg–1 70% N2O Isoflurane Enflurane Halothane 0.20 mg*kg–1 + continuous infusion Propofol mg*kg–1 + continuous infusion 10–55 mg*kg–1 Thiopental –100 A Etomidate –50 50 100 150 Percent change in CBF – CMR –80 200 B –60 –40 –20 20 40 Percent change from baseline • Fig 128.9 Effects of anesthetic agents on cerebral blood flow (CBF) and cerebral metabolic rate (CMR). Volatile agent data regarding CBF for halothane, enflurane, and isoflurane obtained at 1.1 minimal alveolar concentration (MAC) in humans compared with unanesthetized controls and CMR data for the same agents determined in cats compared with nitrous-sedated controls Sevoflurane data on CBF obtained in rabbits compared with morphine-nitrous-sedated controls and CMR data obtained at MAC (A) Desflurane data obtained at MAC (B) Intravenous agent data from human studies compared with unanesthetized controls confirmed histologic injury in of 11 studies but revealed decreased injury after a previous anesthetic in 13 of 16 studies.71 Additionally, neurobehavioral tests were performed in of the 20 studies, of which tested the effects of dexmedetomidine alone and following a prior anesthetic Dexmedetomidine had no negative effect on neurobehavioral testing when used alone and was found to lessen the negative effects induced by a previous anesthetic Though animal studies have been quite suggestive of anesthetic neurotoxicity, human data are less definitive Wilder et al at the Mayo Clinic in Rochester, Minnesota, compared the incidence of learning disabilities in children anesthetized before the age of years to children who had not undergone anesthesia.72 In this article, the incidence of learning disabilities in children with a single exposure was the same as those who did not have an anesthetic exposure However, in patients with greater than one anesthetic exposure, the incidence of learning disabilities was almost two times greater In more recent studies of children with a single anesthetic exposure, Sun et al conducted a bidirectional study of children undergoing inguinal hernia repair before age years and reported no difference in intelligence quotient (IQ) when these patients were compared with their siblings who had not been exposed to anesthesia.73 In a multi-international center study (GAS) of children undergoing hernia repair in infancy anesthetized with either general anesthesia or administered an awake-regional anesthetic, McCann noted no difference between the groups with respect to a full-scale IQ on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III), at years of age.74 In the Mayo Anesthesia Safety in Kids (MASK) study, Warner used propensity matching from a population-based cohort of children undergoing a variety of surgical procedures and reported no effect on full-scale IQ.75 A few studies have reported on the effects of multiple anesthetic exposures before years of age as well as age of exposure with regard to neurotoxicity vulnerability The end points used in these studies were different; consequently, comparison of results is difficult Glatz, in a large-scale study of children in Sweden, noted a small, insignificant difference in school grades and IQ test scores 75a The magnitude of the difference was the same after multiple exposures, and age of exposure did not appear to be a factor However, differences in outcome were more affected by sex, maternal educational level, or month of birth during the same year O’Leary conducted a large-scale study of Canadian schoolchildren and noted that children years old or older at the time of their first surgery had increased odds of an early developmental vulnerability compared with unexposed children (odds ratio, 1.05; 95% confidence interval, 1.01–1.10) There was no increase in odds of early developmental vulnerability with increasing frequency of exposure.75b 1542 S E C T I O N X I V Pediatric Critical Care: Anesthesia Principles in the Pediatric Intensive Care Unit Currently, much remains to be determined with respect to specific anesthetic agents, threshold values for toxicity with regard to dose, number of exposures, patient age vulnerability, and patient risk factors Cardiovascular Effects Historically, inhalational anesthesia was associated with a higher rate of cardiac arrest, bradycardia, and hypotension in infants and children than in adults; these effects were noted to be dose dependent.73–76 Many of these effects can be attributed to the use of halothane, which is no longer commonly used.77 While isoflurane was associated with reduction in systemic vascular resistance, contractility, and blood pressure, cardiac index was better preserved in comparison with halothane.78 At equipotent concentrations (1 MAC), desflurane and isoflurane attenuate the baroresponse in children.79 The hemodynamic profile of sevoflurane in children is similar to isoflurane In a retrospective study of 3548 congenital heart disease (CHD) patients undergoing cardiac MRI under general anesthesia (GA), cardiac index (CI) and left ventricular ejection fraction (LVEF) were measured and compared with a subset of patients within the CHD group who were sedated as well as healthy controls Mean CI was significantly lower in the GA group without significant change in LVEF.80 Compared with awake values, anesthetized children had a 30% decrease in arterial blood pressure at MAC of desflurane with a minimal change in heart rate Rapid increases in desflurane resulted in transient increases in arterial blood pressure and heart rate attributed to both increased sympathetic and renin angiotensin system activity.79 Cardiovascular adverse effects related to mechanical ventilation strategies were demonstrated in rats using biomarkers such as Btype natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), and endothelin-1 (ET-1) BNP increased with both high and low positive end-expiratory pressure (PEEP) compared with ventilated controls VEGF was influenced by high PEEP, hyperoxemia, hypoxemia, and hypocapnia, whereas a change in ET-1 was found only in the setting of hypoxemia This indicates that various mechanical ventilation strategies may adversely influence both the cardiovascular and respiratory systems.81 Intravenous anesthetic agents have frequently been employed for maintenance of hemodynamic stability, specifically opioids A more variable response is noted with dexmedetomidine and a typically negative effect with propofol administration A study of premature infants undergoing patent ductus arteriosus ligation reported the safety and efficacy of fentanyl anesthesia.82 Similarly, high-dose fentanyl (50–75 mg/kg) and sufentanil (5–10 mg/kg) in children with CHD decreased heart rate by only 7% and MAP by 9% Furthermore, pulmonary vascular resistance decreased as well.13 Dexmedetomidine produces a biphasic blood pressure response, an initial increase in blood pressure followed by a decrease, which returns to baseline within minutes Heart rate, however, remains low with bolus dexmedetomidine This response is attributed to the initial stimulation of a2b-receptors, resulting in vasoconstriction and, subsequently, a more powerful response at the a2a-receptors, which causes sympatholysis A bolus dose of 0.5 mg/kg dexmedetomidine administered to patients undergoing endomyocardial biopsy caused an increase within minute in systolic and diastolic blood pressure, systolic and diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and systemic vascular resistance but returned to baseline by minutes after injection Only heart rate decreased following injection and remained lower after minutes No significant changes were noted in central venous pressure or pulmonary vascular resistance.83 The heart rate and blood pressure of 17 pediatric patients on a continuous infusion of dexmedetomidine were analyzed at various points No cardiac conduction abnormalities were found However, a 20% decrease in heart rate from baseline occurred in 35% of patients, but this was not statistically significant over time Only a single patient required discontinuation of infusion due to low heart rate Blood pressure changes were variable, with a statistically significant increase in systolic blood pressure by 0.4 mm Hg/h of infusion.84 The most common adverse effects of dexmedetomidine are hypotension and bradycardia, which are more significant in the setting of underlying cardiac disease or use in conjunction with other negative chronotropic agents (propofol, succinylcholine, digoxin).85–87 Bloor et al noted no hemodynamic response to a 0.7 mg/kg per hour infusion of dexmedetomidine, but a mg/kg bolus dosing resulted in an increase in MAP and a decrease in heart rate.88 Bolus doses of 0.25, 0.5, 1.0, and 2.0 mg/kg were administered to healthy males; MAP decreased 14%, 16%, 23%, and 27%, respectively Following a mg/kg bolus dose, cardiac output decreased by 20% within the first minute but returned to 90% of baseline by 60 minutes A mg/kg bolus dose resulted in a 60% decrease in cardiac output that returned to 85% of baseline within 60 minutes In 30 infants and children undergoing cardiopulmonary bypass randomized to receive dexmedetomidine (1 mg/kg load, 0.5 mg/kg per hour infusion) or placebo, plasma cortisol, norepinephrine, epinephrine, and glucose levels were significantly lower in the dexmedetomidine group.89 Additionally, dexmedetomidine has been reported to have antiarrhythmic effects in the perioperative period and may be useful for terminating reentrant supraventricular tachycardia.90,91 In contrast, propofol has a well-described cardiac depressant effect Induction doses of propofol (2–3 mg/kg) can result in a 10% to 15% decrease in MAP as well as bradycardia There is a modest negative inotropic effect due to antagonism of b-adrenergic receptors and calcium channels.92 Prolonged infusions of greater than 48 hours and rates of mg/kg per hour have been associated with propofol-related infusion syndrome (PRIS) The syndrome is characterized by severe bradycardia resulting in heart failure, metabolic acidosis, hyperlipidemia, rhabdomyolysis, and subsequent hyperkalemia and renal failure.93–95 Pediatric patients appear to be more susceptible than adults to PRIS due to low glycogen stores and need for fat metabolism.96 Risk factors for PRIS include respiratory failure, traumatic brain injury, or other critical illness Triggering agents such as catecholamine and steroid infusion have also been associated with the syndrome.97 This reaction has been attributed to mitochondrial electron transport inhibition and impaired oxygen utilization with subsequently decreased ATP production, mitochondrial lipid metabolism, and accumulation of arrhythmogenic and toxic long fatty acid chains.92,98–100 PRIS management requires prompt recognition and discontinuation of the infusion with aggressive supportive care, including inotropes, fluids, pacing, hemodialysis, and even extracorporeal membrane oxygenation.40,101,102 Respiratory, Gastrointestinal, and Renal Effects While evidence of neurologic and cardiovascular effects is certainly more vast, anesthetic agents are able to modify other organ systems as well As previously mentioned, potential adverse respiratory effects related to mechanical ventilation technique were CHAPTER 128 Anesthesia Effects on Organ Systems demonstrated by altered levels of BNP, VEGF, and ET-1.81 Furthermore, significant increases in airway resistance have been reported in children with known reactive airway disease when anesthetized with desflurane.103 In a study comparing desflurane and sevoflurane with laryngeal mask airway, respiratory events were similar However, more children experienced laryngospasm and mild desaturation in the desflurane group.104 Children undergoing MRI experienced significantly less frequent adverse airway events with a propofol anesthetic versus isoflurane.105 Dexmedetomidine appears to have minimal effect on respiration and may be useful in the setting of upper airway obstruction.106 In a systematic review of randomized controlled trials comparing general anesthesia with volatile anesthetic agents or intravenous agents, the occurrence of postoperative nausea and vomiting was significantly less with intravenous agents.107 A study of 150 children demonstrated that pH parameters (number of reflux episodes minutes, duration of longest reflux episode, time pH ,4 and fraction of time pH ,4) significantly increased in the first hour after anesthesia.108 Furthermore, epidural lidocaine was compared with epidural saline in rats in the setting of intestinal ischemia and subsequent ileus This study found that rats who received epidural lidocaine resolved their ileus much more rapidly than those that did not, indicating that epidural lidocaine not only aids in the treatment of ischemic pain but also in recovery of function.109 In a review of 32 published reports of surgical patients, the evidence based on basic measures of renal function, BUN, and creatinine indicated an absence of renal toxicity during sevoflurane anesthesia.110 Sevoflurane-induced renal toxicity due to its fluoride metabolite was unlikely in a study in which fluoride levels were measured in children after sevoflurane anesthesia.111 Sevoflurane anesthesia over a period of hours in pediatric patients with normal renal function produced compound A, a known renal toxin, in concentrations of 15 ppm or less These patients showed no evidence of abnormal renal function up to 24 hours.112 In a meta-analysis of postoperative pediatric cardiac patients, dexmedetomidine was associated with a significantly lower incidence of acute kidney injury (AKI).113 Intraoperative infusion of dexmedetomidine was also associated with less AKI, measured by estimated glomerular filtration rate and serum creatinine, than in control groups who did not receive dexmedetomidine during pediatric cardiac surgery.114 Finally, dexmedetomidine decreases 1543 renin and vasopressin levels, promotes diuresis, and reduces sympathetic tone.115 In summary, the anesthetic care of ICU patients requires that both intensivists and anesthesiologists have an intimate knowledge of intensive care and anesthetic principles and methods employed throughout the perioperative setting Specific therapeutic goals can only be achieved with these principles in mind and an understanding of a critically ill patient’s ongoing pathology and preexisting conditions Anesthetic agents have a multitude of effects on several organ systems ranging from benign or fatal cardiovascular changes to potential neurotoxic or neuroprotective impacts This chapter reviewed several of the most commonly used anesthetic agents throughout the perioperative period and the expansive impact that they may have on the critically ill patient Key References Drummond JC, Dao AV, Roth DM, et al Effect of dexmedetomidine on cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans Anesthesiology 2008;108(2):225-232 Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits J Neurosci 2003;23(3):876-882 McCann ME, de Graaff JC, Dorris L, et al Neurodevelopmental outcome at years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): An international, multicentre, randomised, controlled equivalence trial Lancet 2019;393:664-77 Rackow H, Salanitre E, Green LT Frequency of cardiac arrest associated with anesthesia in infants and children Pediatrics 1961;28:697-704 Ross AK, Davis PJ, Dear Gd GL et al Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures Anesth Analg 2001;93(6):1393-1401 Stollings LM, Jia LJ, Tang P, Dou H, Lu B, Xu Y Immune modulation by volatile anesthetics Anesthesiology 2016;125(2):399-411 Warner DO, Zaccariello MJ, Katusic SK, et al Neuropsychological and behavioral outcomes after exposure of young children to procedures requiring general anesthesia: The Mayo Anesthesia Safety in Kids (MASK) Study Anesthesiology 2018;129:89-105 Weinberg GL Treatment of local anesthetic systemic toxicity (LAST) Reg Anesth Pain Med 2010;35(2):188-193 The full reference list for this chapter is available at ExpertConsult.com e1 References Rappaport BA, Suresh S, Hertz S, Evers AS, Orser BA Anesthetic neurotoxicity—clinical implications of animal models N Engl J Med 2015;372(9):796-797 Stollings LM, Jia LJ, Tang P, Dou H, Lu B, Xu Y Immune modulation by volatile anesthetics Anesthesiology 2016;125(2):399-411 Suleiman MS, Zacharowski K, Angelini GD Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics Br J Pharmacol 2008;153(1):21-33 Zwass MS, Fisher DM, Welborn LG, et al Induction and maintenance characteristics of anesthesia with desflurane and nitrous oxide in infants and children Anesthesiology 1992;76(3):373-378 Chrysostomou C, Di Filippo S, Manrique AM, et al Use of dexmedetomidine in children after cardiac and thoracic surgery Pediatr Crit Care Med 2006;7(2):126-131 Chrysostomou C, Sanchez De Toledo J, Avolio T, et al Dexmedetomidine use in a pediatric cardiac intensive care unit: can we use it in infants after cardiac surgery? Pediatr Crit Care Med 2009;10(6): 654-660 Dyck JB, Maze M, Haack C, Azarnoff DL, Vuorilehto L, Shafer SL Computer-controlled infusion of intravenous dexmedetomidine hydrochloride in adult human volunteers Anesthesiology 1993;78(5): 821-828 Dyck JB, Maze M, Haack C, Vuorilehto L, Shafer SL The pharmacokinetics and hemodynamic effects of intravenous and intramuscular dexmedetomidine hydrochloride in adult human volunteers Anesthesiology 1993;78(5):813-820 Diaz SM, Rodarte A, Foley J, Capparelli EV Pharmacokinetics of dexmedetomidine in postsurgical pediatric intensive care unit patients: preliminary study Pediatr Crit Care Med 2007;8(5):419-424 10 Kuratani N, Oi Y Greater incidence of emergence agitation in children after sevoflurane anesthesia as compared with halothane: a meta-analysis of randomized controlled trials Anesthesiology 2008;109(2):225-232 11 Kharasch ED, Hankins DC, Thummel KE Human kidney methoxyflurane and sevoflurane metabolism Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity Anesthesiology 1995;82(3):689-699 12 Davis PJ, Cook DR, Stiller RL, Davin-Robinson KA Pharmacodynamics and pharmacokinetics of high-dose sufentanil in infants and children undergoing cardiac surgery Anesth Analg 1987;66(3):203-208 13 Hickey PR, Hansen DD Fentanyl- and sufentanil-oxygen-pancuronium anesthesia for cardiac surgery in infants Anesth Analg 1984; 63(2):117-124 14 Moore RA, Yang SS, McNicholas KW, Gallagher JD, Clark DL Hemodynamic and anesthetic effects of sufentanil as the sole anesthetic for pediatric cardiovascular surgery Anesthesiology 1985;62(6): 725-731 15 Ross AK, Davis PJ, Dear Gd GL et al Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures Anesth Analg 2001;93(6):1393-1401 16 Ivani G, Ferrante FM The American Society Of Regional Anesthesia and Pain Medicine and the European Society Of Regional Anaesthesia and Pain Therapy Joint Committee recommendations for education and training in ultrasound guided regional anesthesia: why we need these guidelines? Reg Anesth Pain Med 2009;34(1):8-9 17 Ivani G, Mosseti V Pediatric regional anesthesia Minerva Anestesiol 2009;75(10):577-583 18 Sites BD, Chan VW, Neal JM, et al The American Society of Regional Anesthesia and Pain Medicine and the European Society Of Regional Anaesthesia and Pain Therapy Joint Committee recommendations for education and training in ultrasound-guided regional anesthesia Reg Anesth Pain Med 2009;34(1):40-46 19 Willschke H, Bösenberg A, Marhofer P, et al Ultrasonographicguided ilioinguinal/iliohypogastric nerve block in pediatric anesthesia: what is the optimal volume? Anesth Analg 2006;102(6): 1680-1684 20 De Negri P, Ivani G, Tirri T, Favullo L, Nardelli A New drugs, new techniques, new indications in pediatric regional anesthesia Minerva Anestesiol 2002;68(5):420-427 21 Ecoffey C Local anesthetics in pediatric anesthesia: an update Minerva Anestesiol 2005;71(6):357-360 22 Shah RD, Suresh S Applications of regional anaesthesia in paediatrics Br J Anaesth 2013;111(suppl 1):i114-i124 23 Weinberg GL Treatment of local anesthetic systemic toxicity (LAST) Reg Anesth Pain Med 2010;35(2):188-193 24 Hoyert DL, Heron MP, Murphy SL, Kung HC Deaths: final data for 2003 Natl Vital Stat Rep 2006;54(13):1-120 25 Ward JD Pediatric issues in head trauma New Horiz 1995;3(3): 539-545 26 Muzzi DA, Losasso TJ, Dietz NM, Faust RJ, Cucchiara RF, Milde LN The effect of desflurane and isoflurane on cerebrospinal fluid pressure in humans with supratentorial mass lesions Anesthesiology 1992;76(5):720-724 27 Matta BF, Heath KJ, Tipping K, Summors AC Direct cerebral vasodilatory effects of sevoflurane and isoflurane Anesthesiology 1999; 91(3):677-680 28 Karsli C, Luginbuehl I, Farrar M, Bissonnette B Cerebrovascular carbon dioxide reactivity in children anaesthetized with propofol Paediatr Anaesth 2003;13(1):26-31 29 Kennedy C, Sokoloff L An adaptation of the nitrous oxide method to the study of the cerebral circulation in children; normal values for cerebral blood flow and cerebral metabolic rate in childhood J Clin Invest 1957;36(7):1130-1137 30 Bedforth NM, Girling KJ, Skinner HJ, Mahajan RP Effects of desflurane on cerebral autoregulation Br J Anaesth 2001;87(2):193-197 31 Wong GT, Luginbuehl I, Karsli C, Bissonnette B The effect of sevoflurane on cerebral autoregulation in young children as assessed by the transient hyperemic response Anesth Analg 2006;102(4):1051-1055 32 Gupta S, Heath K, Matta BF Effect of incremental doses of sevoflurane on cerebral pressure autoregulation in humans Br J Anaesth 1997;79(4):469-472 33 Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell DW Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia Anesthesiology 1995;83(1):66-76 34 Nishiyama T, Matsukawa T, Yokoyama T, Hanaoka K Cerebrovascular carbon dioxide reactivity during general anesthesia: a comparison between sevoflurane and isoflurane Anesth Analg 1999;89(6):1437-1441 35 Hendrich KS, Kochanek PM, Melick JA, et al Cerebral perfusion during anesthesia with fentanyl, isoflurane, or pentobarbital in normal rats studied by arterial spin-labeled MRI Magn Reson Med 2001;46(1):202-206 36 Engelhard K, Werner C, Möllenberg O, Kochs E Effects of remifentanil/ propofol in comparison with isoflurane on dynamic cerebrovascular autoregulation in humans Acta Anaesthesiol Scand 2001;45(8):971-976 37 Scheller MS, Todd MM, Drummond JC Isoflurane, halothane, and regional cerebral blood flow at various levels of PaCO2 in rabbits Anesthesiology 1986;64(5):598-604 38 Scheller MS, Tateishi A, Drummond JC, Zornow MH The effects of sevoflurane on cerebral blood flow, cerebral metabolic rate for oxygen, intracranial pressure, and the electroencephalogram are similar to those of isoflurane in the rabbit Anesthesiology 1988;68(4):548-551 39 Rampil IJ, Lockhart SH, Eger EI II, Yasuda N, Weiskopf RB, Cahalan MK The electroencephalographic effects of desflurane in humans Anesthesiology 1991;74(3):434-439 40 Abrahams JM, Reiter GT, Acker MA, Sinson GP Propofol J Neurosurg 2002;96(6):1160-1161; author reply 1161 41 Alkire MT, Haier RJ, Barker SJ, Shah NK, Wu JC, Kao YJ Cerebral metabolism during propofol anesthesia in humans studied with positron emission tomography Anesthesiology 1995;82(2):393-403; discussion 27A 42 Dam M, Ori C, Pizzolato G, et al The effects of propofol anesthesia on local cerebral glucose utilization in the rat Anesthesiology 1990;73(3):499-505 ... pressure followed by a decrease, which returns to baseline within minutes Heart rate, however, remains low with bolus dexmedetomidine This response is attributed to the initial stimulation of a2b-receptors,... decreased by 20% within the first minute but returned to 90% of baseline by 60 minutes A mg/kg bolus dose resulted in a 60% decrease in cardiac output that returned to 85% of baseline within 60 minutes... groups with respect to a full-scale IQ on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III), at years of age.74 In the Mayo Anesthesia Safety in Kids (MASK) study,