Elizabeth Visco

Cerebral autoregulation in pediatric traumatic brain injury

Objective: The aims of this study were to document the incidence of impaired cerebral autoregulation in children with traumatic brain injury using transcranial Doppler ultrasonography and to examine the relationship between autoregulatory capacity and outcome in children following traumatic brain injury. Design: Prospective cohort study. Setting: Harborview Medical Center (level I pediatric trauma center) in Washington state. Patients: Thirty-six children <15 yrs old with traumatic brain injury: Glasgow Coma Scale score <9 (n = 12, group 1), Glasgow Coma Scale score 9–12 (n = 12, group 2), and Glasgow Coma Scale score 13–15 (n = 12, group 3). Interventions: Cerebral autoregulation testing was conducted during extracranial surgery. Mean middle cerebral artery flow velocities were measured using transcranial Doppler as mean arterial pressure was increased to whichever variable was greater: 20 above baseline or a set value (80 mm Hg for <9 yrs and 90 mm Hg for 9–14 yrs). Autoregulatory capacity was quantified by the Autoregulatory Index. Autoregulatory Index <0.4 was considered impaired cerebral autoregulation. Discharge outcome using the Glasgow Outcome Scale score was considered good if the Glasgow Outcome Scale score was ≥4. Measurements and Main Results: Twenty-four (67) of 36 children had an Autoregulatory Index ≥0.4. The incidence of impaired cerebral autoregulation was 42 (five of 12) in group 1, 42 (five of 12) in group 2, and 17 (two of 12) in group 3. Ten (42) of the 24 children with intact cerebral autoregulation had a good outcome compared with only one of 12 (8) children with impaired cerebral autoregulation (p = .04). Six of 12 (50) children with impaired cerebral autoregulation had hyperemia compared with one of 24 (4) children with intact cerebral autoregulation (p < .01). Hyperemia was associated with poor outcome (p = .01). Conclusions: The incidence of impaired cerebral autoregulation was greatest following moderate to severe traumatic brain injury. Impaired cerebral autoregulation was associated with poor outcome. Hyperemia was associated with impaired cerebral autoregulation and poor outcome.

Propofol: relation between brain concentrations, electroencephalogram, middle cerebral artery blood flow velocity, and cerebral oxygen extraction during induction of anesthesia.

Background The potential benefit of propofol dose regimens that use physiologic pharmacokinetic modeling to target the brain has been demonstrated in animals, but no data are available on the rate of propofol distribution to the brain in humans. This study measured the brain uptake of propofol in humans and the simultaneous effects on electroencephalography, cerebral blood flow velocity (Vmca), and cerebral oxygen extraction. Methods Seven subjects had arterial and jugular bulb catheters placed before induction. Electroencephalography and Vmca were recorded during induction with propofol while blood samples were taken from both catheters for later propofol analysis. Brain uptake of propofol was calculated using mass balance principles, with effect compartment modeling used to quantitate the rate of uptake. Results Bispectral index (electroencephalogram) values decreased to a minimum value of approximately 4 at around 7 min from the onset of propofol administration and then slowly recovered. This was accompanied by decreases in Vmca, reaching a minimum value of approximately 40% of baseline. Cerebral oxygen extraction did not change, suggesting parallel changes in cerebral metabolism. There was slow equilibrium of propofol between the blood and the brain (t1/2keo of 6.5 min), with a close relation between brain concentrations and bispectral index, although with considerable interpatient variability. The majority of the decreases in Vmca, and presumably cerebral metabolism, corresponded with bispectral index values reaching 40–50 and the onset of burst suppression. Conclusion Description of brain distribution of propofol will allow development of physiologic pharmacokinetic models for propofol and evaluation of dose regimens that target the brain.

Graded Hypercapnia and Cerebral Autoregulation during Sevoflurane or Propofol Anesthesia

BackgroundHypercapnia abolishes cerebral autoregulation, but little is known about the interaction between hypercapnia and autoregulation during general anesthesia. With normocapnia, sevoflurane (up to 1.5 minimum alveolar concentration) and propofol do not impair cerebral autoregulation. This study aimed to document the level of hypercapnia required to impair cerebral autoregulation during propofol or sevoflurane anesthesia. MethodsEight healthy subjects received a remifentanil infusion and were anesthetized with propofol (140 &mgr;g · kg−1 · min−1) and sevoflurane (1.0–1.1% end tidal) in a randomized crossover study. Ventilation was adjusted to achieve incremental increases in arterial carbon dioxide partial pressure (Paco2) until autoregulation was impaired. Cerebral autoregulation was tested by increasing the mean arterial pressure (MAP) from 80 to 100 mmHg with phenylephrine while measuring middle cerebral artery flow velocity by transcranial Doppler. The autoregulation index, which has a value ranging from 0 to 1, representing absent to perfect autoregulation, was calculated, and an autoregulation index of 0.4 or less represented significantly impaired autoregulation. ResultsThe threshold Paco2 to significantly impair cerebral autoregulation ranged from 50 to 66 mmHg. The threshold averaged 56 ± 4 mmHg (mean ± SD) during sevoflurane anesthesia and 61 ± 4 mmHg during propofol anesthesia (P = 0.03). Carbon dioxide reactivity measured at a MAP of 100 mmHg was 30% greater than that at a MAP of 80 mmHg. ConclusionsEven mild hypercapnia can significantly impair cerebral autoregulation during general anesthesia. There is a significant difference between propofol anesthesia and sevoflurane anesthesia with respect to the effect of hypercapnia on cerebral autoregulation. This difference occurs at clinically relevant levels of Paco2. When inducing hypercapnia, carbon dioxide reactivity is significantly affected by the MAP.

Cerebral Autoregulation and Co2 Reactivity in Anterior and Posterior Cerebral Circulation During Sevoflurane Anesthesia

The purpose of the study was to compare cerebral autoregulation (CA) and CO2 reactivity (CO2R) between the anterior and posterior circulation under sevoflurane anesthesia. We studied 9 adult ASA physical status I patients (22–47 yr) scheduled for elective orthopedic surgery. Blood flow velocity in the middle cerebral artery (Vmca) and in the basilar artery (Vba) were measured using transcranial Doppler ultrasonography. For CA testing, arterial blood pressure was increased using phenylephrine infusion. CA was quantified with the autoregulatory index (ARI). CO2R was investigated at Paco2 of 30 ± 2.8 mm Hg, 39.4 ± 2.6 mm Hg, and 48.7 ± 2.8 mm Hg. Linear regression analysis was used for CO2R. We found ARI was preserved in both arteries: ARImca (middle cerebral artery) = 0.72 ± 0.2; ARIba (basilar artery) = 0.66 ± 0.2; P = 0.5. With regard to CO2R, Vmca increased with slope of 1.7 cm/s/mm Hg Paco2, Vba increased with slope of 1.5 cm/s/mm Hg Paco2; P = 0.83. Absolute Vmca was higher compared with Vba; P < 0.05. We conclude that in healthy individuals under 0.5 MAC of sevoflurane and small-dose remifentanil: 1) mean flow velocities of BA are less than those of MCA; 2) autoregulation and CO2R are preserved in the basilar artery and are similar to those of MCA.

The variability of cerebrovascular reactivity with posture and time.

Transcranial Doppler (TCD) ultrasonography has been used in a variety of clinical contexts to assess cerebrovascular reserve by measuring carbon dioxide reactivity. Reproducibility with time and altered position of the patient is examined in the present study. Carbon dioxide reactivity was determined in 10 healthy volunteers using TCD. Hypocarbia was produced by voluntary hyperventilation, and hypercarbia was produced by rebreathing from a circuit primed with 7% carbon dioxide. Each patient was studied in the supine position twice (1 week apart) and once in the seated position. Carbon dioxide reactivity was determined from linear regression analysis of paired middle cerebral artery flow velocity and end-tidal carbon dioxide values. Analysis of covariance for repeated measures was used for statistical analysis. Both the absolute slope and the relative slope (absolute slope expressed as a percentage of flow velocity at 40 mm Hg) were compared. In the supine position, flow velocity, absolute and relative slopes, and mean arterial pressure were similar from one week to the next at all carbon dioxide levels. In contrast, flow velocity, mean arterial pressure (adjusted for hydrostatic gradient), and absolute slope were decreased in the seated position (p < 0.05). No difference was observed when the relative slope was used for comparison. We conclude that absolute carbon dioxide reactivity is reproducible over time but may be influenced by position. Relative reactivity (relative slope), however, was both time and position independent.

Rocuronium versus Succinylcholine-Atracurium for Tracheal Intubation and Maintenance Relaxation During Propofol Anesthesia

STUDY OBJECTIVES To compare the onset and offset time (clinical duration), and intubating conditions obtained with rocuronium bromide 0.6 mg/kg and succinylcholine 1.0 mg/kg after induction with propofol and fentanyl; and to compare rocuronium with atracurium for maintenance during propofol anesthesia. DESIGN Prospective, open-label, parallel group comparative, randomized study. SETTING Operating rooms of a university hospital. PATIENTS 30 ASA physical status I and II adult patients scheduled for elective surgeries with general anesthesia. INTERVENTIONS Patients premedicated with midazolam 2 mg were anesthetized with fentanyl 2 microg/kg followed by propofol 2.5 mg/kg and muscle relaxants. Group 1 (n = 15) received succinylcholine 1.5 mg/kg and Group 2 (n = 16) received rocuronium bromide 0.6 mg/kg. Intubation was performed 60 seconds after the administration of muscle relaxant. Patients in Group 1 received atracurium and patients in Group 2 received rocuronium for maintenance if required. MEASUREMENTS The ease of intubation was scored using a scale of 1 to 4. Onset and offset time monitored with evoked twitch response of the adductor pollicis were recorded. MAIN RESULTS Intubation was successful in all patients and there was no difference in scores between the two groups. Although onset time was shorter with succinylcholine than with rocuronium, neuromuscular blockade was successfully antagonized in both groups, and the recovery profile was not different between the two groups. CONCLUSIONS Rocuronium bromide at a dose of 0.6 mg/kg, when used with propofol and fentanyl for induction, provides intubating conditions similar to succinylcholine 1.0 mg/kg at 1 minute. The actual onset time and offset time, however, are significantly longer with rocuronium. There was no difference between atracurium and rocuronium as a maintenance drug. Rocuronium is suitable for surgical procedures greater than 30 minutes, eliminating the need for an additional relaxant to succinylcholine.

Chronic cocaine exposure alters carbon dioxide reactivity but does not affect cerebral blood flow autoregulation in anesthetized dogs

BACKGROUND Cocaine use is common in trauma victims. Consequently, understanding how cocaine alters normal physiology is important to providing appropriate medical care for these patients. This study was designed to identify how chronic cocaine exposure alters cerebrovascular physiology. METHODS Ten dogs (seven experimental, three control) were studied. Transcranial Doppler was used to measure CO2 reactivity and autoregulation of cerebral blood flow velocity (CBFvel). Measurements were made in anesthetized animals (0.6% or 1.8% isoflurane in oxygen and intravenous fentanyl) at baseline before cocaine exposure and then at weekly intervals for 4 weeks. During the 4-week study period, cocaine was administered intravenously four times per day. RESULTS Cocaine did not alter autoregulation of CBFvel in response to changes in mean arterial pressure. However, cocaine markedly impaired CO2 reactivity in three of the seven animals. In this subset of animals, increasing Paco2 decreased CBFvel, which is consistent with vasoconstriction rather than vasodilation. CONCLUSION Chronic cocaine exposure does not alter autoregulation of CBFvel but does alter CO2 reactivity in a subset of susceptible animals. If confirmed in humans, these findings have implications for traumatic brain injury patients who are chronic cocaine users. Specifically, the findings suggest that hyperventilation could exacerbate intracranial hypertension in a subset of these patients.

Cerebral Autoregulation and CO2 Reactivity in Anterior and Posterior Cerebral Circulation During Sevoflurane Anesthesia: Gender Differences

Posterior Cerebral Circulation During Sevoflurane Anesthesia: Gender Differences Irene Rozet, Elizabeth Visco, Monica S. Vavilala, Arthur M. Lam. Departments of Anesthesiology; Pediatric; and 5Neurological Surgery, University of Washington, Seattle, WA. The aim: To compare cerebral autoregulation (CA) and CO2 reactivity (CO2 R) in the anterior and posterior circulation under steady-state sevoflurane anesthesia between males and females. Methods: Six females (21-44 yo, ASA I-II), scheduled for elective orthopedic surgery were studied and compared to eight males (19-47 yo, ASA I-II). Blood flow velocity in the middle cerebral artery (Vmca) and in the basilar artery (Vba) were measured using Transcranial Doppler (TCD) ultrasonography. For CA testing, blood pressure was increased using phenylephrine infusion at normocapnia. The autoregulatory index (ARI) was used for assessment of CA. CO2 R was investigated at PaCO2 of 29±3, 39±2, and 46±5mm Hg. Linear regression analysis was used for CO2 R. Student t-test and one-way ANOVA with repeated measures were used for comparison, p<.05 was considered significant. Results: At normocapnia, Vmca and Vba were significantly higher in females, compared with males, p=0.02, and Vmca was higher than Vba in both genders, p<0.05. There was no gender difference in autoregulation, which was preserved in both MCA and BA (males vs. females: ARImca : 0.7±0.2 vs. 0.75±0.35, p=0.3; ARIba: 0.6±0.2 vs. 0.76±0.33, p=0.8). CO2 R slope of Vba in males did not significantly differ from that in females (1.5 vs. 1.8 cm/sec/mmHg, p=0.83). However, the CO2R slope of Vba in females was significantly higher than of Vmca in both genders (females Vba vs. females Vmca: 1.8 vs. 1.32, p=0.03; vs. males Vmca: 1.8 vs. 1.3 cm/sec/mmHg PaCO2, p=0.02). Conclusions: In healthy females 0.5MAC of sevoflurane and low-dose remifentanil: 1) Mean flow velocities of BA and MCA are higher than in males; 2) Autoregulation is preserved in BA and is similar to that of MCA in both genders; 3) CO2 R of BA in females is higher than that of MCA in females, but this difference was not observed in males.