Postoperative cognitive deficit after cardiopulmonary bypass with preserved cerebral oxygenation: a prospective observational pilot study.

BACKGROUND: Neurologic deficits after cardiac surgery are common complications. Aim of this prospective observational pilot study was to investigate the incidence of postoperative cognitive deficit (POCD) after cardiac surgery, provided that relevant decrease of cerebral oxygen saturation (cSO2) is avoided during cardiopulmonary bypass. METHODS: cSO2 was measured by near infrared spectroscopy in 35 patients during cardiopulmonary bypass. cSO2 was kept above 80% of baseline and above 55% during anesthesia including cardiopulmonary bypass. POCD was tested by trail making test, digit symbol substitution test, Ray's auditorial verbal learning test, digit span test and verbal fluency test the day before and 5 days after surgery. POCD was defined as a decline in test performance that exceeded - 20% from baseline in two tests or more. Correlation of POCD with lowest cSO2 and cSO2 - threshold were determined explorative. RESULTS: POCD was observed in 43% of patients. Lowest cSO2 during cardiopulmonary bypass was significantly correlated with POCD (p = 0.015, r2 = 0.44, without Bonferroni correction). A threshold of 65% for cSO2 was able to predict POCD with a sensitivity of 86.7% and a specificity of 65.0% (p = 0.03, without Bonferroni correction). CONCLUSIONS: Despite a relevant decrease of cerebral oxygen saturation was avoided in our pilot study during cardiopulmonary bypass, incidence of POCD was comparable to that reported in patients without monitoring. A higher threshold for cSO2 may be needed to reduce the incidence of POCD.

Postoperative neurocognitive dysfunction in elderly patients after xenon versus propofol anesthesia for major noncardiac surgery: a double-blinded randomized controlled pilot study.

BACKGROUND: Postoperative cognitive dysfunction (POCD) in elderly patients after noncardiac surgery is a common problem. The noble gas xenon has been demonstrated to exert substantial neuroprotective properties in animal studies. Therefore, this study was designed to assess POCD after xenon anesthesia in comparison to propofol in elderly patients undergoing major noncardiac surgery. METHODS: After approval of the local ethical committee was obtained, 101 patients (American Society of Anesthesiologists physical status I-III; age, 65-83 yr) undergoing elective abdominal or urologic surgery (duration, > 2 h) were enrolled into this randomized, double-blinded controlled pilot study. Patients received anesthesia with sufentanil and either propofol or xenon and were assessed before treatment and 1, 6, and 30 days after treatment using a neuropsychological test battery based on previous studies investigating POCD. RESULTS: There were no significant differences in terms of age, American Society of Anesthesiologists status, education, duration of surgery, administered analgetics, and preoperative neurocognitive status between study groups. POCD as classified was present in 22 patients (44%) of the xenon group versus 25 patients (50%) of the propofol group 1 day after treatment, in 6 xenon patients (12%) versus 9 propofol patients (18%) 6 days after treatment, and in 3 xenon patients (6%) versus 6 propofol patients (12%) 30 days after treatment. These differences were not statistically significant. CONCLUSION: Postoperative impairment of neurocognitive function was observed in a substantial proportion of elderly patients even 30 days after treatment. Xenon-based anesthesia was not associated with decreased incidence of POCD in comparison to propofol.

Dexmedetomidine does not reduce epileptiform discharges in adults with epilepsy.

There are limited data on the effect of dexmedetomidine on epileptiform electroencephalogram (EEG). The aim of this study was to investigate if dexmedetomidine will abolish epileptiform discharges in patients with medically refractory seizure disorders who were candidates for surgery to resect foci of epileptic activity. With approval from the Institutional Review Board and written informed consent, we enrolled 5 patients with medically intractable seizures who were undergoing continuous video/EEG monitoring. EEG and hemodynamic values were recorded from 15 minutes before, during, and for 60 minutes after a 60-minute dexmedetomidine infusion. Epileptiform discharges were counted for each 15-minute epoch during the study. Two of the 5 patients had a discrete spike focus in each hemisphere. Thus, we analyzed the activity of 7 distinct foci. Epileptiform activity did not decrease in any individual focus during dexmedetomidine infusion. Although dexmedetomidine did not have a statistically significant effect on interictal epileptiform activity for the group as a whole, the activity of 4 foci increased during dexmedetomidine infusion. Dexmedetomidine did not reduce seizure focus activity and thus may be a suitable anesthetic adjunct during seizure surgery.

Effect of peripheral vasoconstriction on pulse oximetry.

OBJECTIVE: We tested the hypothesis that peripheral vasodilation has an effect on arterial oxygen saturation measurements by pulse oximetry, independent of temperature. METHODS: Study 1 compared finger arterial oxygen saturation values (SpO(2)), before and after peripheral vasoconstriction while temperature was kept constant. This was achieved by administering dexmedetomidine (peripheral vasoconstrictor) to 16 volunteers given general anesthesia. Study 2 compared SpO(2) before and after peripheral vasodilation (brachial plexus block) in a neurally denervated left hand and a neurally innervated right hand in ten awake volunteers. In both studies measurements were also made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmission through a finger (LTF), finger temperature and of hemodynamic variables. RESULTS: In Study 1, systolic blood pressure, SpO(2) and LTF values increased (vasoconstriction) during dexmedetomidine infusion, (P<0.0001 for all) while there were no changes in finger temperature. In Study 2, in the left hand (axillary block), temperature increased by 1.9 +/- 1.6 degrees C (P=0.004), SpO(2) decreased by 2.5 +/- 1.0 % (P<0.0001) and LTF values decreased (vasodilation) by 42 +/- 8 % (P<0.0001) after axillary block. Simultaneously, the axillary block did not induce any changes in temperature, SpO(2) or LTF values in the neurally innervated right hand. CONCLUSIONS: Our results demonstrate that finger pulse oximeter SpO(2) measurements can be affected by peripheral vascular tone independent of temperature. The mechanism for this effect remains speculative and unproven.

Alpha-2B adrenoceptor polymorphism and peripheral vasoconstriction.

OBJECTIVES: Alpha-2B adrenoceptors (AR) mediate vasoconstriction in the mice. A human alpha-2B AR deletion (D) variant has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction upon alpha-2 AR activation. This study tested the hypothesis that alpha-2 AR activation will induce enhanced vasoconstriction in carriers of the alpha-2B AR DD genotype, compared to carriers of the II or the DI genotypes. METHODS: We administered 1 microg/kg dexmedetomidine (an alpha-2 agonist) intravenously to 80 surgical patients in whom sympatholytic effects of the drug were attenuated by general anesthesia. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmission through a finger (LTF) and of hemodynamic variables. RESULTS: Dexmedetomidine increased LTF (vasoconstriction), induced an initial increase in systolic blood pressure and decreased heart rate in all genotype groups (P<0.0001 for all). Three min after the start of dexmedetomidine infusion, the increase in LTF was more pronounced (P=0.014) in the DD group compared to the DI and II groups. There were no significant differences in LTF values between the groups at the end of or 5 min after dexmedetomidine infusion. There were no differences in systolic blood pressure or heart rate values between the groups during or after the dexmedetomidine infusion. CONCLUSIONS: The results of this study confirm that the alpha-2 agonist dexmedetomidine induced marked peripheral vasoconstriction. Subjects with the alpha 2B DD genotype had an enhanced vasoconstrictive response at the beginning of dexmedetomidine infusion. However, this enhanced vasoconstrictive response was not sustained throughout or after the 15-min dexmedetomidine infusion.

Effect of alpha2B-adrenoceptor polymorphism on peripheral vasoconstriction in healthy volunteers.

BACKGROUND: Alpha-2B adrenoceptor is the vasoconstrictive subtype in the mouse. Human alpha2B-AR deletion (D) allele has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction on alpha2 activation. The goal of this study was to test the hypothesis that alpha2B-adrenoceptor activation induces enhanced vasoconstriction in carriers of the DD genotype, compared with carriers of the insertion/insertion (II) genotype. METHODS: The authors administered increasing doses of dexmedetomidine (targeting plasma concentrations of 0.15, 0.3, 0.6, and 1.2 ng/ml) to 16 healthy young volunteers (8 carrying the alpha2B DD genotype, 8 carrying the II genotype) in whom sympatholytic effects of the drug were attenuated by general anesthesia. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmitted through a finger, finger blood flow by venous occlusion plethysmography, and hemodynamic variables. RESULTS: All concentration of dexmedetomidine increased light transmitted through the finger (vasoconstriction) and systolic blood pressure and decreased heart rate in both groups (P < 0.001 for all). Dexmedetomidine reduced finger arterial inflow only in the DD group (P < 0.001). Dexmedetomidine had no effect on finger venous outflow or venous capacitance. There were no significant differences between the II and DD groups in any of the variables. CONCLUSIONS: The results of this study confirm the alpha2 agonist induced vasomotor and hemodynamic effects in peripheral vasculature. However, the results do not support the hypothesis that alpha2B-adrenoceptor polymorphism has an effect on peripheral vasoconstriction in humans.

Intraoperative clonidine administration to neurosurgical patients.

The goals of this two-part study were to determine the dose of clonidine to prevent postoperative shivering after mild hypothermia and to evaluate the effect of clonidine on recovery from anesthesia in patients undergoing surgery for intracranial lesions. We enrolled 48 patients undergoing elective supratentorial neurosurgical procedures into one of two studies. In study 1 (n=14) we determined the ED50 of clonidine to prevent postoperative shivering after mild hypothermia (35 degrees C) using Dixon's up-and-down method. Clonidine dose for the first study patient was 3 microg/kg. The dose was then adjusted in 1-microg/kg increments for the following patients. Shivering was assessed for 1 h postoperatively. Study 2 (n=34) was a prospective, randomized, double-blind, placebo controlled study to evaluate the effect of 3 microg/kg clonidine on recovery from anesthesia. At the beginning of dural closure, patients randomly received a 15-min infusion of either clonidine or normal saline. Recovery variables were studied for 2 h after the end of anesthesia. The ED50 of clonidine to prevent shivering was 1.1 +/- 1.5 microg/kg in neurosurgical patients whose target core temperature was 35 degrees C at the end of surgery. Compared with saline, 3 microg/kg of clonidine administered to neurosurgical patients 1 h before the end of anesthesia did not delay emergence from anesthesia nor did it have clinically significant sedative or hemodynamic effects. Our results imply that clonidine may be used in neurosurgical patients to prevent postoperative shivering after mild hypothermia.