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Desflurane increases cerebral blood flow velocity when used for rapid emergence from propofol anesthesia in children

[Le desflurane augmente la vitesse circulatoire cérébrale quand il est utilisé pour un réveil rapide après l’anesthésie au propofol chez des enfants]

From the Department of Anaesthesia, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Address correspondence to: Dr. Ross Barlow, Department of Anaesthesia, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G IX8, Canada. Phone: 416-813-7445; Fax: 416-813-7543; E-mail: ross.barlow{at}sickkids.ca

	Abstract

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Purpose: Desflurane may be used to replace propofol at the end of anesthesia to facilitate rapid emergence. This study determined the effect of administering desflurane during emergence of anesthesia on middle cerebral artery blood flow velocity (Vmca) in children anesthetized with propofol.

Methods: Thirty healthy chilren aged one to six years scheduled for orchidopexy or hypospadias repair under general anesthesia were enrolled. Anesthesia was maintained with a propofol infusion targeting an estimated serum level of 3 µg·mL^–1, remifentanil 0.2 µg·kg^–1·min^–1 and a caudal epidural block. Transcranial Doppler sonography was used to measure Vmca at five-minute intervals. In half the patients, propofol was substituted with desflurane 1 MAC, 30 min prior to the end of the surgical procedure. Once steady-state had been achieved recordings of Vmca, heart rate, and mean arterial pressure were resumed. Upon termination of the surgical procedure, the maintenance agent was discontinued and recordings continued at one-minute intervals during emergence of anesthesia.

Results: There were no demographic differences between the two groups. Vmca increased from 37.2 ± 3.1 cm·sec^–1 to 57.7 ± 4.1 cm·sec^–1 when propofol was changed to desflurane (P < 0.01). Upon emergence of anesthesia, Vmca decreased from 57.8 ± 4.2 cm·sec^–1 to 37.8 ± 3.2 cm·sec^–1 in the desflurane group (P < 0.01) but remained unchanged in the propofol group.

Conclusion: Desflurane is associated with an increase in cerebral blood flow velocity when used to facilitate rapid emergence following a propofol infusion in children. This may be of clinical significance in patients with intracranial pathology.

	Introduction

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RAPID emergence from anesthesia may be desirable in the neurosurgical setting. Desflurane may be used to replace propofol at the end of anesthesia to facilitate rapid recovery. The effect of propofol and desflurane on cerebral blood flow velocity (CBFV) during general anesthesia has been studied.^1–4 However, to date no studies have reported the effect of these agents during emergence from anesthesia in infants and children. Propofol has cerebral vasoconstrictive properties and appears to be ideal for neurosurgical procedures where control of intracranial pressure (ICP) is indicated.¹ Desflurane is a potent cerebral vasodilator and may contribute to increases in cerebral blood flow and volume.^2–4 This study was designed to test the null hypothesis that when propofol is replaced with desflurane for emergence from anesthesia in children, there is no effect on middle cerebral artery blood flow velocity (Vmca).

	Methods

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With Research Ethics Board approval and written informed parental consent, 30 ASA I or II children aged one to six years scheduled for orchidopexy or hypospadias repair were enrolled. Patients with cardiovascular or neurological disease, a history of premature birth or contraindication to regional anesthesia were excluded. In each child, anesthesia was induced with sevoflurane in 100% oxygen. Standard anesthetic monitors were applied, an iv catheter was placed and propofol 2.5 mg·kg^–1 was given. Rocuronium 1.0 mg·kg^–1 was used to facilitate tracheal intubation. Intermittent positive pressure ventilation was instituted with 35% oxygen in air and sevoflurane was discontinued. Peak airway pressure was maintained constant at 15 cm H₂O with zero positive end-expiratory pressure and the ventilatory rate was adjusted to maintain an end-tidal CO₂ of 35 mmHg. Anesthesia was maintained with a propofol infusion regimen consisting of 15 mg·kg^–1·hr^–1 for the first 15 min, 13 mg·kg^–1·hr^–1 for the next 15 min, followed by 11 mg·kg^–1·hr^–1 for the next 30 min and 10 mg·kg^–1·hr^–1 thereafter. This was based on a pediatric pharmacokinetic model designed to target an estimated steady-state serum propofol concentration of 3 µg·mL^–1.5 Each patient also received a remifentanil 0.5 µg·kg^–1 bolus followed by a 0.2 µg·kg^–1·min^–1 infusion.⁶

Each child received a caudal epidural block with 1.0 mL·kg^–1 of 0.25% bupivicaine without epinephrine in order to eliminate the cerebrovascular response to surgical stimulation. Surgery was allowed to commence 20 min after the caudal block was performed and the analgesic effect was assumed to be successful if, upon skin incision, the heart rate (HR) and mean arterial pressure (MAP) did not vary more than 5% from baseline. Fluid deficits secondary to fasting and ongoing losses were replaced with an initial bolus of lactated Ringer’s solution 8 mL·kg^–1 followed by a maintenance infusion of 10 mL·kg^–1·hr^–1. Further fluids were given as necessary to maintain normotension. A convective air warmer (Bair Hugger 500/OR, USA) and conductive heating mattress (Gaymar, New York, NY, USA) were used to maintain normothermia.

A transcranial Doppler probe (TCD; Neuroguard, Medasonics, Fremont, CA, USA) was placed to measure Vmca at the M1 segment using a 2-MHz emitted ultrasonic frequency. Simultaneous recordings of Vmca, HR, and MAP were taken at five-minute intervals throughout the study period. Patients were randomized using a computer generated random number table. In half the patients, propofol was substituted with desflurane, age-adjusted to 1 MAC, 30 min before the end of the surgical procedure (desflurane-substituted group). In the other half, the propofol infusion was continued (propofol group). Fifteen minutes were allowed to achieve steady-state and recordings of Vmca, HR, and MAP were resumed at five-minute intervals. Upon termination of the surgical procedure, the maintenance agent was discontinued and recordings continued at one-minute intervals for five minutes, during anesthetic emergence in both groups under remifentanil alone.

Statistical analysis
Demographics and data with parametric values are presented as mean ± SD. The number of patients needed to demonstrate a direct effect on Vmca during changes in anesthetic agent was calculated with the assumption that a 20% change would be clinically relevant. Based on a statistical power of 0.8, an ₂ = 0.05 and a ß = 0.2, seven patients per group was suggested. The Student’s unpaired t test, repeated measure ANOVA and Tukey-Kramer tests were used where appropriate. P < 0.05 was accepted as significant.

	Results

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The mean age of propofol and desflurane-substituted patients was 2.4 ± 1.3 yr and 2.3 ± 1.2 yr, and the mean weight was 13.1 ± 3.6 kg and 13.2 ± 3.5 kg, respectively. All patients were male. The caudal block was successful in all patients and TCD measurements were completed in all children. Vmca increased from 37.2 ± 3.1 cm·sec^–1 to 57.7 ± 4.1 cm·sec^–1 when propofol was changed to desflurane (P < 0.01; Figure, events 4–6). Upon anesthetic emergence, Vmca decreased from 57.8 ± 4.2 cm·sec^–1 to 37.8 ± 3.2 cm·sec^–1 in the desflurane group (P < 0.01) but remained unchanged in the propofol group (Figure, events 7–11). MAP and HR did not change significantly during desflurane substitution or in either group during emergence (Table).

View larger version (24K): [in this window] [in a new window]   FIGURE Changes in middle cerebral artery blood flow velocity (Vmca) in the propofol (PPF) and the desflurane (DES)-substituted group intraoperatively and during emergence of anesthesia. Baseline measurements of Vmca during propofol maintenance for both groups are represented by events 1–3. Events 4, 5 and 6 correspond to the switch from propofol to desflurane in the DES-substituted group. Discontinuation of the anesthetic agent and emergence from anesthesia are represented by events 7–11. *P < 0.01 compared to the PPF group.

	Discussion

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Propofol has been shown to decrease both cerebral metabolism and blood flow in adults.⁷ Cerebrovascular reactivity to carbon dioxide is highly preserved under propofol anesthesia in children.⁸ These properties make it an ideal anesthetic agent for children undergoing neurosurgical procedures. Due to significant pharmacokinetic and pharmacodynamic differences between children and adults however, propofol doses and infusion rates required to achieve a certain target blood concentration are higher for pediatric patients.^9,10 In addition, the context-sensitive half-life of propofol is longer in children than in adults, presumably due to altered compartment volumes of distribution.⁹ This implies that recovery from a propofol infusion may be slower in children than in adults, which may limit its usefulness in prolonged neurosurgical procedures.

Desflurane has pharmacokinetic properties that allow for rapid emergence which is often desirable in the neurosurgical setting. Infants anesthetized with desflurane demonstrated a faster recovery when compared to those anesthetized with isoflurane.¹¹ However, some of the potentially undesirable cerebrovascular properties of desflurane deserve mention. Cerebral blood pressure autoregulation is impaired at 1.0 MAC, and almost completely abolished at 1.5 MAC desflurane in adults.² Desflurane has been shown to cause a dose-dependent increase in Vmca and HR in children,³ an effect which appears to be enhanced with the addition of nitrous oxide.¹² CBFV increases when propofol is replaced with desflurane for maintenance of anesthesia in pediatric patients.¹³

Factors known to alter CBFV include surgical stimulation, arterial carbon dioxide partial pressure, cardiac output, body temperature, and intrathoracic pressure. End-tidal CO₂ and body temperature remained constant throughout the study period and the caudal epidural block seemed to eliminate the cerebrovascular response to surgical stimulation.

The absence of any significant change in HR or MAP at the time of desflurane substitution or during emergence of anesthesia in either group is likely due to the fact that remifentanil was used as part of a balanced anesthetic technique. Remifentanil has been shown to attenuate the somatic and hemodynamic responses in children at doses used in the current study.⁶ A recent pediatric study has demonstrated that remifentanil 0.2 µg·kg^–1·min^–1 does not alter CBFV.¹⁴ The iv crystalloid administration regimen likely also contributed to the overall hemodynamic stability noted in the current study.

The transient sympathetic hyperactivity observed with desflurane in children is known to persist for up to nine minutes.¹⁵ As such, physiologic variables were recorded no earlier than 15 min after desflurane substitution in order to eliminate this source of error and achieve steady-state concentrations.

The increase in variability of Vmca in the desflurane-substituted group needs to be addressed. Desflurane is known to cause cerebral vasodilatation, perhaps even more so than other volatile agents.^4,16 Physiologically, measurements of flow during vasodilatation would be expected to exhibit greater variability as compared to vasoconstriction, which has a more finite endpoint.

TCD sonography is a non-invasive and reproducible technique that has been validated as a surrogate measure of cerebral blood flow.¹⁷ To reduce inter-patient variability in Vmca measurements, the TCD examination was performed by one of three experienced researchers. Fixing the TCD probe in place using an established frame reduced intra-patient variability.¹⁸

In conclusion, the current study demonstrates that desflurane is associated with an increase in CBFV when used to facilitate rapid emergence following a propofol infusion for maintenance of general anesthesia in children. However, this transient increase in CBFV returns to control levels once desflurane is reduced to subanesthetic concentrations during emergence. This should be taken into consideration when contemplating the administration of desflurane in the pediatric neurosurgical setting, particularly in those patients with decreased intracranial compliance.

	Acknowledgments

 
The authors would like to thank their colleagues from the Department of Urology and Operating Room nurses for their assistance with this study.

	Footnotes

 
Presented in part at the American Society of Anesthesiologists Annual Meeting, San Francisco, USA, October, 2003.

Accepted for publication March 11, 2004. Revision accepted May 18, 2004.

	References

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This Article Abstract Résumé de cet Article Full Text (PDF) Submit a scholarly reply Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Barlow, R. Articles by Bissonnette, B. Search for Related Content PubMed PubMed Citation Articles by Barlow, R. Articles by Bissonnette, B.