British Journal of Anaesthesia

BJA Advance Access published online on January 4, 2008
British Journal of Anaesthesia, doi:10.1093/bja/aem343

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Comparative effects of propofol vs dexmedetomidine on cerebrovascular carbon dioxide reactivity in patients with septic shock

Y. Kadoi^1,*, S. Saito¹, C. Kawauchi², H. Hinohara² and F. Kunimoto²

¹ Department of Anesthesiology
² Division of Intensive Care, Gunma University Hospital, Gunma, Japan

^* Corresponding author: Department of Anesthesiology, Gunma University Hospital, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. E-mail: kadoi{at}med.gunma-u.ac.jp

Accepted for publication September 14, 2007.

	Abstract

Top Abstract Introduction Methods Results Discussion Funding Acknowledgement References

 
Background: The use of sedative drugs is reportedly related to altered cerebrovascular CO₂ reactivity. The present study examined the comparative effects of propofol vs dexmedetomidine on cerebrovascular CO₂ reactivity in patients with septic shock.

Methods: A total of 20 patients with septic shock who required mechanical ventilation were included in this study. Sedation during mechanical ventilation was maintained using either propofol or dexmedetomidine. A 2.5 MHz pulsed transcranial Doppler probe was attached to the head of the patient at the right temporal window for continuous measurement of mean blood flow velocity in the middle cerebral artery (V_mca). After establishing baseline values of V_mca and cardiovascular haemodynamics, end-tidal CO₂ was increased by decreasing ventilatory frequency by 5–8 bpm.

Results: The absolute and relative CO₂ reactivity values in patients with septic shock were lower for both propofol and dexmedetomidine than those for control groups, with significant differences between these values in the two septic shock groups (absolute CO₂ reactivity in septic shock under propofol: 2.6 (SD 0.3) cm s^–1 mm Hg^–1; absolute CO₂ reactivity in septic shock under dexmedetomidine: 2.0 (0.3) cm s^–1 mm Hg^–1; P<0.01).

Conclusions: This study showed that cerebrovascular CO₂ reactivity was lower under dexmedetomidine sedation than under propofol sedation during almost identical sedation in patients with septic shock.

Keywords: brain, blood flow; carbon dioxide, measurement; sedation

	Introduction

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Control of arterial CO₂ levels (Pa_CO2) is often used to control cerebral blood flow (CBF) and cerebral blood volume during surgery and in intensive care units (ICUs).^1–4 Altered CBF in response to changes in Pa_CO2 is defined as cerebrovascular CO₂ reactivity.⁵

The central nervous system (CNS) is one of the first organs to be affected by sepsis, although the mechanisms by which this occurs remain unresolved.^{6 7} One proposed mechanism that might account for CNS dysfunctions induced by sepsis is impaired cerebral autoregulation.^8–11 Whether cerebral autoregulation remains intact in patients with severe sepsis or septic shock remains controversial. Matta and Stow⁸ examined cerebral CO₂ reactivity in 10 patients during the early stages of sepsis, and found that cerebral CO₂ reactivity and pressure autoregulation remained intact. In contrast, Terborg and colleagues⁹ showed that severe sepsis and septic shock severely reduced the cerebrovascular CO₂ reactivity, independent of changes in mean arterial pressure (MAP).

Many different sedative drugs are administered to mechanically ventilated patients in the ICU.¹²¹³ Some published data have shown that sedative drugs used in the ICU, such as propofol or diazepam, and fentanyl or dexmedetomidine, can alter cerebrovascular CO₂ reactivity.¹³ Iida and colleagues¹⁴¹⁵ showed a constrictive effect of dexmedetomidine on cerebral arterioles in dogs. We have previously reported that propofol exerts differential vasoconstrictive effects in elderly subjects compared with young subjects.¹⁶ These findings indicate that different sedatives are likely to exert different effects on cerebrovascular CO₂ reactivity. We thus hypothesized that cerebrovascular CO₂ reactivity would differ between propofol and dexmedetomidine sedation in patients with septic shock. As no previous studies have provided such data, this study compared the effects of propofol and dexmedetomidine on cerebrovascular CO₂ reactivity in patients with septic shock.

	Methods

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After obtaining approval from the ethics committee of our institution, written, informed consent was obtained from all patients. Subjects comprised 20 patients with septic shock within 72 h of admission to the ICU. In addition, all studies were performed within 24 h after the diagnosis of septic shock.

Patients with septic shock were defined according to American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM) criteria.¹⁷ Routine monitoring, including electrocardiography, invasive arterial pressure, central venous pressure, end-tidal CO₂ (PE'_CO2) and pulse oximetry, was done for all patients.

The 20 septic shock patients were prospectively randomized into two groups: the propofol group (n=10), receiving 1.0 mg kg^–1 i.v. bolus of propofol over 10 min, followed by continuous infusion at a rate of 1–3 mg kg^–1 h^–1; and the dexmedetomidine group (n=10), receiving 0.01 µg kg^–1 i.v. bolus of dexmedetomidine over 10 min, followed by continuous infusion of 0.3–0.5 mg kg^–1 h^–1. As controls, 20 patients without sepsis were also monitored. These control patients were ICU patients who required mechanical ventilation for respiratory failure. Control patients were likewise randomized into propofol and dexmedetomidine groups (n=10 each). Sedation regimens for control patients were identical to those for septic shock patients. To maintain haemodynamic stability, all patients in control and septic shock groups received inotropic agents such as dopamine, dobutamine, or adrenaline. Target systolic arterial blood pressure for all patients was >80 mm Hg. All patients received mechanical ventilation using a Servo 300 ventilator (Siemens, Danvers, MA, USA) in volume-controlled ventilation mode with a PEEP of 5–10 cm H₂O. Target oxygenation variables were Pa_O2>60 mm Hg and arterial oxygen saturation was >90%. Measurement of cerebrovascular CO₂ reactivity was performed 1 h after haemodynamic and respiratory variables stabilized.

To assess the severity of disease and organ dysfunction, Acute Physiology and Chronic Health Evaluation (APACHE II) and multiple organ dysfunction syndrome (MODS) scores were registered.

Target sedation levels in all patients in both groups were Ramsay Score 4 sedation. A bispectral index (BIS) monitor (Aspect Medical Systems, Natic, MA, USA) was used to assess the effects of equipotent doses of propofol and dexmedetomidine in each group.

A 2.5 MHz pulsed transcranial Doppler probe was attached to the head of the patient at the right temporal window and mean blood flow velocity in the middle cerebral artery (V_mca) was measured continuously using a SONOS 5500 2.5 MHz transducer (Hewlett Packard, Andover, MA, USA). After signals were identified at a depth of 45–60 mm, the probe was fixed using a probe folder, to avoid changes to insonating angle. V_mca values at end-expiration were recorded.

After measurement of baseline V_mca and cardiovascular haemodynamic values, PE'_CO2 was increased by reducing ventilatory frequency by 5–8 bpm. This increased PE'_CO2 by 7–10 mm Hg from 34 (3) to 43 (4) mm Hg within several minutes. All measurements were repeated after PE'_CO2 increase and had remained stable for 5–10 min. To confirm alterations in Pa_CO2 by reducing ventilatory frequency, Pa_CO2 was also measured.

Cerebral vasodilatory response to hypercapnia in each patient was calculated as both the absolute change in V_mca and the percentage change from baseline V_mca per millimetre of mercury change in Pa_CO2 using the following formulae:^{18 19}

where V_mca is the difference between flow velocity after Pa_CO2 elevation and baseline flow velocity, and Pa_CO2 is the difference between final and baseline Pa_CO2. The generally accepted value for absolute CO₂ reactivity is a 2.0–5.0 cm change in flow velocity per second per millimetre of mercury under anaesthesia. In addition, the generally accepted value for relative CO₂ reactivity is a 2.5–6.0% change in flow velocity per millimetre of mercury.

Pulsatile index (PI) and V_mca were calculated for all study participants using the following formulae:^{18 19}

Examiners who measured V_mca were blinded to group assignment for each patient. Data obtained in this study were analysed later by an independent researcher who was likewise blinded to group assignment.

Statistical analysis
All data are expressed as mean (SD). A paired t-test or Fisher exact test was used for comparisons between propofol and dexmedetomidine groups. After confirmation of equal variance among groups using the Bartlett test, one-way factorial measure analysis of variance was performed with multiple comparisons. When the F-value was significant, the Bonferroni method was used for multiple comparisons. To eliminate type II errors, each individual P-value was adjusted. Sample size was evaluated after completion of the study, and was calculated based on the hypothesis that absolute CO₂ reactivity in propofol and dexmedetomidine patients would be decreased by 0.5 cm s^–1 mm Hg^–1 compared with that in control patients.¹⁸ The sample size provided 80% power to detect a 20% difference between propofol or dexmedetomidine and control groups with a 5% probability of type a error. P<0.05 was considered statistically significant. All calculations were performed on a Macintosh computer with SPSS (SPSS, Chicago, IL, USA) and StatView 5.0 software (Abacus Concepts, Berkeley, CA, USA).

	Results

Top Abstract Introduction Methods Results Discussion Funding Acknowledgement References

 
Table 1 shows patient characteristics for all groups. All patients in propofol and dexmedetomidine groups displayed readily detectable V_mca flow velocities. All groups were well matched for age, weight, and height. APACHE II and MODS scores were significantly higher in patients with septic shock than those in control patients, but no significant differences in these values were seen among septic shock patients in propofol and dexmedetomidine groups. No significant differences in MAP were identified among any groups.

View this table: [in this window] [in a new window]   Table 1 Patient characteristics for each group. Values are expressed as mean (SD). APACHE II, acute Physiology and Chronic Health Evaluation; MODS, multiple organ dysfunction syndrome; MAP, mean arterial pressure; HR, heart rate, CVP, central venous pressure. *P<0.05 compared with control

 
FI_O2 and PEEP were significantly higher in patients with septic shock than those in control patients. No significant differences in FI_O2 or PEEP were seen between propofol and dexmedetomidine groups with or without septic shock. Dosages of vasopressor drugs were higher in patients with septic shock than those in control patients, but were well matched between septic shock patients in propofol and dexmedetomidine groups.

Table 2 shows the cerebrovascular CO₂ reactivity data in all groups. PI, V_mca, BIS, baseline Pa_CO2 and Pa_CO2, under conditions of hypercapnia were essentially identical among groups.

View this table: [in this window] [in a new window]   Table 2 Comparative effects of propofol and dexmedetomidine on cerebrovascular CO2 reactivity in each group. Values are expressed as mean (SD). BIS, bispectral index; Vmca, mean blood flow velocity in the middle cerebral artery; BP, blood pressure; PI, pulsatile index. *P<0.05 compared with control; **P<0.05 compared with propofol group with sepsis

 
Values for absolute and relative CO₂ reactivity in patients with septic shock in both propofol and dexmedetomidine groups were lower than those in the respective control groups. No significant differences in absolute or relative CO₂ reactivity existed between control patients in propofol and dexmedetomidine groups. In contrast, absolute and relative CO₂ reactivity in patients with septic shock differed significantly between propofol and dexmedetomidine groups, with higher reactivity in the propofol group [absolute CO₂ reactivity in septic shock under propofol: 2.6 (0.3) cm s^–1 mm Hg^–1; absolute CO₂ reactivity in septic shock under dexmedetomidine: 2.0 (0.3) cm s^–1 mm Hg^–1, P<0.01].

	Discussion

Top Abstract Introduction Methods Results Discussion Funding Acknowledgement References

 
The present study showed that cerebrovascular CO₂ reactivity was lower under dexmedetomidine sedation than under propofol sedation in patients with septic shock. In contrast, no differences in cerebrovascular CO₂ reactivity were found in control patients under propofol or dexmedetomidine sedation.

The American College of Critical Care Medicine and the SCCM practice parameters for the optimal use of sedatives and analgesics, which were published in 1995 and revised in 2000, recommend a tiered approach to the use of sedatives and analgesics.¹³ These guidelines recommend that drugs of choice in patients >12 yr old requiring prolonged sedation and analgesia during mechanical ventilation include morphine and fentanyl for i.v. opiate analgesia and propofol for rapid awakening from sedation. The selective -2 agonist, dexmedetomidine, has recently been approved for use as a sedative with analgesic-sparing activity for short-term (<24 h) use in patients receiving mechanical ventilatory support. In addition to sedative effects, dexmedetomidine reduces concurrent analgesic and sedative requirements and produces anxiolytic effects comparable with benzodiazepines.¹³

Some controversial findings have been reported regarding cerebrovascular CO₂ reactivity in patients with septic shock.^8–11 Matta and Stow⁸ showed that cerebral CO₂ reactivity and pressure autoregulation remained intact in patients with sepsis syndrome, providing indirect evidence that at least in the early stages of the syndrome, widespread sepsis-induced vasoparalysis does not involve the cerebral vasculature. In contrast, Terborg and colleagues⁹ showed that severe sepsis and septic shock severely reduced CO₂-induced vasomotor reactivity, independent of changes in MAP. In addition, this impaired vasomotor reactivity was not observed in the absence of sepsis, leading to speculation that such impaired vasomotor reactivity might contribute to the pathogenesis of septic encephalopathy. Bowie and colleagues¹¹ studied 12 sedated and ventilated patients in whom sepsis had been established for >24 h, and found that established sepsis profoundly affects vascular tone and reactivity, not only of the systemic circulation, but also of the cerebral vasculature. They concluded that discrepancies regarding impaired cerebrovascular CO₂ reactivity were attributable to differences in the timing of measurements in relation to the onset of sepsis or disease severity. Brian and colleagues¹⁰ studied the probable mechanisms of impaired vasomotor reactivity during sepsis, and suggested that impaired mechanisms of vasomotor reactivity during sepsis are not accounted for by group B streptococcus-induced reductions in cardiac output or blood pressure, and are mediated by nitric oxide, not prostanoids. The present findings suggest that the degree of intactness of vasomotor reactivity during sepsis must be considered when attempting to control CBF by changing arterial CO₂ levels.

Several studies have evaluated the effects of propofol and dexmedetomidine on cerebrovascular circulation and CO₂ reactivity. Matta and colleagues²⁰ examined the cerebral CO₂ reactivity during propofol-induced electrical silence of the electroencephalography in 10 patients, and found that the cerebral CO₂ reactivity remained intact during propofol anaesthesia. In a study on sheep, Myburgh and colleagues²¹ reported that although constant propofol infusion at 15 mg min^–1 kg^–1 significantly decreased CBF compared with awake conditions, CO₂ reactivity remained intact. In regard to dexmedetomidine, few data are available for the effects of dexmedetomidine on cerebral autoregulation.^{22 23} Zornow and colleagues²³ showed in dogs that despite increased arterial pressure, dexmedetomidine caused marked reductions in CBF when dexmedetomidine has no effect on the cerebral metabolic rate for oxygen. Our study is the first to compare the effects of sedative doses of dexmedetomidine and propofol on CO₂ reactivity in patients with septic shock. The results show that cerebrovascular CO₂ reactivity is lower under dexmedetomidine sedation than under propofol sedation during almost identical levels of sedation in patients with septic shock. This suggests that propofol has a sparing effect on cerebrovascular CO₂ reactivity compared with dexmedetomidine when used as a sedative in patients with septic shock, and thus represents the preferred sedative agent in these patients. In contrast to the differential results between propofol and dexmedetomidine in patients with septic shock, no differential effects were found in controls. This finding has clinical implications in that hypercapnic lung-protective ventilation is currently widely accepted as a ventilatory strategy for acute respiratory distress syndrome. Hypercapnic ventilation has no adverse effect on intracranial pressure (ICP) in patients without septic shock under propofol or dexmedetomidine. In addition, neuroprotective ventilation is sometimes used for patients with raised ICP in patients with brain injury. In patients without septic shock, both propofol and dexmedetomidine would be effective to control ICP. Several mechanisms should be considered for our results. First, dexmedetomidine has a more profound cerebrovascular constrictor effect compared with propofol at our study dosage. Secondly, patient characteristics may have affected our results. In a previous study, we found that the cerebrovascular CO₂ reactivity was lower in elderly patients than in young patients.¹⁶ Hartl and colleagues²⁴ reported markedly lower absolute and relative mean CO₂ reactivities in elderly subjects compared with young subjects, suggesting that aging might have some effects on cerebrovascular CO₂ reactivity. Finally, the use of different dosages compared with those used in our study may have yielded differential effects. Indeed, we have previously shown that differential dosages of propofol exert differential effects on CO₂ reactivity.¹⁶ Altering the dose of dexmedetomidine used in septic shock patients in our study may thus have resulted in different effects on CO₂ reactivity. Therefore, further study is necessary to clarify the differential effects of propofol and dexmedetomidine on cerebrovascular CO₂ reactivity in patients with septic shock.

The cerebrovascular CO₂ reactivity under dexmedetomidine sedation in patients with septic shock was almost within the normal range according to results from our previous studies, even when more profound depression of cerebrovascular CO₂ reactivity occurred with dexmedetomidine than with propofol. However, for clinical situations in ICUs, CBF or volume is sometimes used to manipulate Pa_CO2. The change in Pa_CO2 has larger effects on CBF and volume under propofol sedation than under dexmedetomidine sedation. The clinical relevance of our findings is that maintaining adequate cerebral circulation is important in patients with septic shock, to avoid septic encephalopathy. Extra caution in the choice of sedatives is thus warranted, as these agents might alter cerebral autoregulation in patients with septic shock.

Study limitations
In patients with septic shock, large doses of catecholamines were used to maintain adequate haemodynamics. These large doses of catecholamines may have had some effects on our results.²⁵²⁶ Stephan and colleagues²⁵ showed that norepinephrine and phenylephrine infused to increase arterial pressure in anaesthetized patients failed to show any significant vasoconstrictor effects on cerebral circulation. Although catecholamine dosage was almost identical between propofol and dexmedetomidine groups in septic shock patients, the effects of catecholamines on vasoconstrictor effects in the cerebral circulation cannot be ignored. Further study is needed to clarify the effects of propofol and dexmedetomidine on cerebral circulation using high-dose catecholamines.

This study focused on the comparative effects of propofol and dexmedetomidine on CO₂ reactivity in patients with septic shock, without examining the direct effects of propofol or dexmedetomidine on vasomotor CO₂ reactivity in patients with and without septic shock.

The present study used BIS monitors to achieve identical sedation levels. Whether BIS monitors are suitable for monitoring sedation in the ICU remains controversial. Weatherburn and colleagues²⁷ assessed the effectiveness of a BIS monitor in supporting clinical sedation management decisions in mechanically ventilated ICU patients, and concluded that the use of BIS monitoring did not reduce the amount of sedation used, duration of mechanical ventilation, or duration of ICU stay. Frenzel and colleagues²⁸ examined the utility of BIS in assessing depth of sedation for sedated and mechanically ventilated ICU patients, compared with clinical sedation scores, and showed that BIS was unsuitable for monitoring sedation in a heterogeneous group of surgical ICU patients. However, Venn and colleagues²⁹ showed the efficacy of BIS monitors for defining sedation levels in comparisons between dexmedetomidine and propofol for sedation in the ICU.

Another problem is that the present study did not directly measure the cerebral metabolic rate of oxygen (CMRO₂), and so cannot rule out the possibility that CMRO₂ might have changed during the study period, although factors related to changing CMRO₂, such as anaesthetic depth as assessed by BIS and clinical sedation score or rectal temperature, may not have changed throughout the study period.

Hypocapnia-induced hyperventilation is commonly used to treat increased ICP in the operation theatre or ICU.¹ A recent review³⁰ raised questions about the efficacy of hyperventilation-induced hypocapnia. Laffey and Kavanagh³⁰ suggested that the reduction in ICP might be life-saving in patients with severely elevated ICP. However, hypocapnia-induced brain ischaemia may occur because of vasoconstriction (impaired cerebral perfusion), reduced oxygen release from haemoglobin, and increased neuronal excitability, with the possible release of excitotoxins such as glutamate. In contrast, hypercapnia has been proposed to be beneficial in cases of focal ischaemia by causing vasodilation and increasing blood flow in the ischaemic brain. Conversely, hypercapnia may also decrease blood flow to the ischaemic brain by causing vasodilation in the normal brain and diverting blood flow away from the ischaemic brain.⁵ According to the present findings, controlling CBF by altering Pa_CO2 can be more effectively achieved using propofol rather than dexmedetomidine sedation in the ICU.

In conclusion, we found that cerebrovascular CO₂ reactivity in patients with septic shock was impaired compared with that in patients without septic shock, and that cerebrovascular CO₂ reactivity was lower under dexmedetomidine sedation than under propofol sedation in patients with septic shock.

	Funding

Top Abstract Introduction Methods Results Discussion Funding Acknowledgement References

 
This study was supported in part by grants to Dr Kadoi (grant no. 18591688) from the Japanese Ministry of Education, Culture, Sports, Science and Technology and the Mitsubishi Pharma Research Foundation.

	Acknowledgement

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The authors wish to thank Forte (Tokyo, Japan) for assistance with the manuscript.

	References

Top Abstract Introduction Methods Results Discussion Funding Acknowledgement References

 
1 Kadoi Y, Ide M, Saito S, Shiga T, Ishizaki K, Goto F. Hyperventilation after tourniquet deflation prevents an increase in cerebral blood flow velocity. Can J Anaesth (1999) 46:259–64.[Web of Science][Medline]

2 Kadoi Y, Hinohara H, Kunimoto F, et al. Diabetic patients have an impaired cerebral vasodilatory response to hypercapnia under propofol anesthesia. Stroke (2003) 34:2399–403.[Abstract/Free Full Text]

3 Hinohara H, Kadoi Y, Takahashi K, Saito S, Goto F. Cerebrovascular carbon dioxide reactivity in patients with former stroke under propofol anesthesia. J Clin Anesth (2004) 16:483–7.[CrossRef][Web of Science][Medline]

4 Moppett IK, Mahajan RP. Transcranial Doppler ultrasonography in anaesthesia and intensive care. Br J Anaesth (2004) 93:710–24.[Free Full Text]

5 Brian JE. Carbon dioxide and the cerebral circulation. Anesthesiology (1998) 88:1365–86.[CrossRef][Web of Science][Medline]

6 Kadoi Y, Hinohara H, Kunimoto F, Saito S, Goto F. A cannabinoid antagonist, AM 281, reduces mortality rate and neurological dysfunction after cecal ligation and puncture in rats. Crit Care Med (2005) 33:2629–36.[CrossRef][Web of Science][Medline]

7 Kadoi Y, Saito S. An alteration in the -aminobutyric acid receptor system in experimentally induced septic shock in rats. Crit Care Med (1996) 24:298–305.[CrossRef][Web of Science][Medline]

8 Matta BF, Stow PJ. Sepsis-induced vasoparalysis does not involve the cerebral vasculature: indirect evidence from autoregulation and carbon dioxide reactivity studies. Br J Anaesth (1996) 76:790–4.[Abstract/Free Full Text]

9 Terborg C, Schummer W, Albrecht M, Reinhart K, Weiller C, Rother J. Dysfunction of vasomotor reactivity in severe sepsis and septic shock. Intensive Care Med (2001) 27:1231–4.[CrossRef][Web of Science][Medline]

10 Brian R, Marie L, Anthony B, Robert H, William M. Group B streptococcal sepsis impairs cerebral vascular reactivity to acute hypercarbia in piglets. Pediatr Res (1996) 39:55–63.[Web of Science][Medline]

11 Bowie EA, O'Connor PJ, Mahajan RP. Cerebrovascular reactivity to carbon dioxide in sepsis syndrome. Anaesthesia (2003) 58:261–5.[CrossRef][Web of Science][Medline]

12 Soliman HM, Melot C, Vincent JL. Sedative and analgesic practice in the intensive care unit: the results of a European survey. Br J Anaesth (2001) 87:186–92.[Abstract/Free Full Text]

13 Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med (2002) 30:119–41.[CrossRef][Web of Science][Medline]

14 Iida H, Ohata H, Iida M, Watanabe Y, Dohi S. Direct effects of alpha-1 and alpha-2 adrenergic agonists on spinal and cerebral pial vessels in dogs. Anesthesiology (1999) 91:479–85.[CrossRef][Web of Science][Medline]

15 Iida H, Iida M, Ohata H, Michino T, Dohi S. Effects of dexmedetomidine on cerebral circulation and systemic hemodynamics after cardiopulmonary resuscitation in dogs. J Anesthesia (2006) 20:202–7.[CrossRef]

16 Hinohara H, Kadoi Y, Takahashi K, Saito S, Goto F. Differential effects of propofol on cerebrovascular carbon dioxide reactivity in elderly versus young subjects. J Clin Anesth (2005) 17:85–90.[CrossRef][Web of Science][Medline]

17 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med (1992) 20:864–74.[Web of Science][Medline]

18 Kadoi Y, Takahashi K, Saito S, Goto F. The comparative effects of sevoflurane versus isoflurane on cerebrovascular carbon dioxide reactivity in patients with diabetes mellitus. Anesth Analg (2006) 103:168–72.[Abstract/Free Full Text]

19 Moppett IK, Mahajam RP. Transcranial Doppler ultrasonography in anaesthesia and intensive care. Br J Anaesth (2004) 93:710–24.[Free Full Text]

20 Matta BF, Lam AM, Strebel S, Mayberg TS. Cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced EEG suppression. Br J Anaesth (1995) 74:159–63.[Abstract/Free Full Text]

21 Myburgh JA, Upton RN, Ludbrook GL, Martinez A, Grant C. Cerebrovascular carbon dioxide reactivity in sheep: effect of propofol or isoflurane anaesthesia. Anaesth Intensive Care (2002) 30:413–21.[Web of Science][Medline]

22 Obata H, Iida H, Dohi S, Watanabe Y. Intravenous dexmedetomidine inhibits cerebrovascular dilation induced by isoflurane and sevoflurane in dogs. Anesth Analg (1999) 89:370–7.[Abstract/Free Full Text]

23 Zornow MH, Fleischer JE, Scheller MS, Nakakimura K, Drummond JC. Dexmedetomidine an alpha 2-adernergic agonist decreases cerebral blood flow in the isoflurane-anesthetized dog. Anesth Analg (1990) 70:624–30.[Abstract/Free Full Text]

24 Hartl WH, Furst H. Application of transcranial Doppler sonography to evaluate cerebral hemodynamics in carotid artery disease. Comparative analysis of different hemodynamic variables. Stroke (1995) 26:2293–7.[Abstract/Free Full Text]

25 Stephan PS, Christoph K, Bruno B, Gabriela T, Dubravka D. The impact of systemic vasoconstrictors on the cerebral circulation of anesthetized patients. Anesthesiology (1998) 89:67–72.[CrossRef][Web of Science][Medline]

26 Moppett IK, Wild MJ, Sherman RW, Laccer JA, Miller K, Mahajam RP. Effects of ephedrine, dobutamine and dopexamine on cerebral hemodynamics: transcranial Doppler studies in healthy volunteers. Br J Anaesth (2004) 92:39–44.[Abstract/Free Full Text]

27 Weatherburn C, Endacott R, Bailey M. The impact of bispectral index monitoring on sedation administration in mechanically ventilated patients. Anaesth Intensive Care (2007) 35:204–8.[Web of Science][Medline]

28 Frenzel D, Greim CA, Sommer C, Bauerle K, Roewer N. Is the bispectral index appropriate for monitoring the sedation level of mechanically ventilated surgical ICU patients? Anaesth Intensive Care (2002) 28:178–83.

29 Venn RM, Grounds RM. Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinical perceptions. Br J Anaesth (2001) 87:684–90.[Abstract/Free Full Text]

30 Laffey JG, Kavanagh BP. Hypocapnia. N Eng J Med (2002) 347:43–53.[Free Full Text]

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