Yuji Kadoi

Diabetic Patients Have an Impaired Cerebral Vasodilatory Response to Hypercapnia Under Propofol Anesthesia

Background and Purpose— The purpose of this study was to examine the effects of diabetes mellitus and its severity on the cerebral vasodilatory response to hypercapnia. Methods— Thirty diabetic patients consecutively scheduled for elective major surgery were studied. After induction of anesthesia, a 2.5-MHz pulsed transcranial Doppler probe was attached to the patient’s head at the right temporal window, and mean blood flow velocity of the middle cerebral artery (Vmca) was measured continuously. After the baseline Vmca, arterial blood gases, and cardiovascular hemodynamic values were measured, end-tidal CO2 was increased by reducing ventilatory frequency by 2 to 5 breaths per minute. Measurements were repeated when end-tidal CO2 increased and remained stable for 5 to 10 minutes. Results— Significant differences were observed in absolute and relative CO2 reactivity between the diabetes and control groups (absolute CO2 reactivity: control, 2.8±0.7; diabetes mellitus, 2.1±1.3; P <0.01; relative CO2 reactivity: control, 6.3±1.4; diabetes mellitus, 4.5±2.7; P <0.01, Mann-Whitney U test). Significant differences were also found between diabetic patients with retinopathy and those without retinopathy in absolute (P =0.002) and relative (P =0.002) CO2 reactivity, glycosylated hemoglobin (P =0.0034), and fasting blood sugar (P =0.01) (Scheffé’s test, Mann-Whitney U test). There was an inverse correlation between absolute CO2 reactivity and glycosylated hemoglobin (r =0.69, P <0.001). Conclusions— Insulin-dependent diabetic patients have an impaired vasodilatory response to hypercapnia compared with that of the control group, and the present findings suggest that their degree of impairment is related to the severity of diabetes mellitus.

The comparative effects of propofol versus thiopental on middle cerebral artery blood flow velocity during electroconvulsive therapy.

Electroconvulsive therapy provokes abrupt changes in both systemic and cerebral hemodynamics. An anesthetic that has a minor effect on cerebral hemodynamics might be more suitable for patients with intracranial complications, such as cerebral aneurysm. The purpose of our present study was to compare the effects of thiopental and propofol on cerebral blood flow velocity. We continuously compared cerebral blood flow velocity at the middle cerebral artery (MCA) during electroconvulsive therapy, using propofol (1 mg/kg, n = 20) versus thiopental (2 mg/kg, n = 20) anesthesia. Systemic hemodynamic variables and flow velocity at the MCA were measured until 10 min after the electrical shock. Heart rate and arterial blood pressure increased in the thiopental group until 5 min after the electrical shock. In the propofol group, an increase in mean blood pressure was observed to 1 min after the electrical shock. Mean flow velocity at the MCA decreased after anesthesia in both groups, and increased at 0.5–3 min after the electrical shock in the thiopental group and at 0.5 and 1 min after the shock in the propofol group. The flow velocities at 0.5–5 min after the electrical shock were significantly more rapid in the thiopental group compared with the propofol group. {abs} Implications Cerebral blood flow velocity change, measured by transcranial Doppler sonography during electroconvulsive therapy, was minor using propofol anesthesia compared with barbiturate anesthesia. Propofol anesthesia may be suitable for patients who cannot tolerate abrupt cerebral hemodynamic change.

An alteration in the gamma-aminobutyric acid receptor system in experimentally induced septic shock in rats.

OBJECTIVE To investigate the role of the brain gamma-aminobutyric acid receptor system in septic shock. DESIGN Prospective, controlled study. SETTING Animal laboratory. SUBJECTS Twenty-one male Wistar rats (7 wks old) were randomized to three groups: group 1 (n = 7, control); group 2 (n = 7, sham-operated); group 3 (n = 7, cecal ligation and puncture group). INTERVENTIONS Under light ether anesthesia, the rats were treated as described above. Twenty-four hours after treatment, the rats were killed by decapitation. Plasma amino acid concentrations were measured using the collected blood. The brain was excised as rapidly as possible, and separated into forebrain, cerebellum, and brain stem. The brain gamma-aminobutyric acid concentration was measured at each of the three regions. Using 3H-musimol, which is a gamma-aminobutyric acid receptor agonist, as a radioligand, the gamma-aminobutyric receptor densities were measured in these three regions by a radio-receptor assay. MEASUREMENTS AND MAIN RESULTS The concentrations of the branch-chain amino acids (leucine, isoleucine, valine) were lower in the cecal ligation and puncture group than in the control and sham operated groups. The concentrations of the sulfur-containing amino acids (cysteine and taurine) were increased in the cecal ligation and puncture group compared with the other two groups, but the methionine concentration was increased in the sham-operated and the cecal ligation and puncture groups compared with the control group (p < .05). The plasma gamma-aminobutyric acid concentration was not detectable in any of the three groups. The ammonia concentration was greater in the cecal ligation and puncture group than in the other two groups. There was no significant difference in the brain gamma-aminobutyric acid concentration among the three groups. The maximum number of binding sites in the forebrain of the cecal ligation and puncture group was higher than in the other two groups at both high- and low-affinity sites (control group: high-affinity sites 0.34 +/- 0.03, low-affinity sites 2.93 +/- 0.28; sham-operated group: high-affinity sites 0.35 +/- 0.03, low-affinity sites 2.73 +/- 0.18; cecal ligation and puncture group: high-affinity sites 0.59 +/- 0.13, low-affinity sites 3.53 +/- 0.21; mean +/- SEM pmol/mg protein) (p < .05). There were no significant differences observed in other regions of the brain (cerebellum and brain stem) in the three groups. The dissociation constants for 3H-musimol were almost unchanged in the three groups. CONCLUSIONS An increase in the gamma-aminobutyric acid-A receptor density was observed in the forebrain of the cecal ligation and puncture model rats. This alteration may be closely related to the pathogenesis of brain dysfunction during septic shock.

Effects of hypothermic and normothermic cardiopulmonary bypass on brain oxygenation

BACKGROUND In this study, we assessed the effects of normothermia and hypothermia during cardiopulmonary bypass (CPB) both on internal jugular venous oxygen saturation (SjvO2) and the regional cerebral oxygenation state (rSO2) estimated by near infrared spectroscopy (NIRS). METHODS Thirty patients scheduled for elective coronary artery bypass graft surgery (CABG) were randomly divided into two groups. Group 1 (n = 15) underwent surgery for normothermic (> 35 degrees C) CPB, and group 2 (n = 15) underwent surgery for hypothermic (30 degrees C) CPB, and alpha-stat regulation was applied. A 4.0-French fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor the SjvO2 value. To estimate the rSO2 state, a spectrophotometer probe was attached to the mid-forehead. SjvO2 and rSO2 values were then collected simultaneously using a computer. RESULTS Neither the cerebral desaturation time (duration during SjvO2 value below 50%), nor the ratio of the cerebral desaturation time to the total CPB time significantly differed (normothermic group: 18+/-6 min, 15+/-6%; hypothermic group: 17+/-6 min, 13+/-6%, respectively). The rSO2 value in the normothermic group decreased during the CPB period compared with the pre-CPB period. The rSO2 value in the hypothermic group did not change throughout the perioperative period. CONCLUSIONS These findings suggest that near infrared spectroscopy might be sensitive enough to detect subtle changes in regional cerebral oxygenation.

Decrease in jugular venous oxygen saturation during normothermic cardiopulmonary bypass predicts short-term postoperative neurologic dysfunction in elderly patients ☆

OBJECTIVES We sought to examine whether the decrease in jugular venous oxygen saturation (SjvO(2)) during cardiopulmonary bypass (CPB) can be used to predict short-term and long-term postoperative cognitive disorders in elderly patients. BACKGROUND It has been reported that elderly patients might be more susceptible to hypoperfusion during CPB. METHODS One hundred eighty-five patients scheduled for elective coronary artery bypass graft surgery were studied. Group 1 (n = 56) was young (<50 years old), group 2 (n = 67) was middle-aged (50 to 69 years old) and group 3 (n = 62) was elderly (>70 years old). After induction of anesthesia, a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to monitor SjvO(2) continuously. Hemodynamic variables and arterial and jugular venous blood gases were measured at seven time points. RESULTS The cerebral desaturation time (duration when SjvO(2) was <50%) and the ratio of the cerebral desaturation time to the total CPB time in group 3 were significantly different from those in groups 1 and 2 (group 1: 20 +/- 6 min and 16 +/- 5%; group 2: 19 +/- 7 min and 14 +/- 6%; group 3: 34 +/- 9 min and 24 +/- 7%, respectively; p < 0.05). Also, age (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.0 to 1.8, p = 0.02) and desaturation time (OR 1.3, 95% CI 1.0 to 1.4, p = 0.03) were perioperative factors in relation to short-term cognitive impairment. However, age and desaturation time were not perioperative factors in relation to long-term cognitive impairment. CONCLUSIONS Reduced SjvO(2) was associated with short-term cognitive dysfunction in elderly patients.

Reduction of cerebral hyperemia with anti-hypertensive medication after electroconvulsive therapy

Purpose: Several different anti-hypertensive regimens have been introduced for the prevention of systemic hyperdynamic responses after electrically induced seizures. In the present study, the effects of anti-hypertensive medications on cerebral circulation were studied.Methods: Systemic blood pressure was controlled by several anti-hypertensive medications, nicardipine, prostaglandin EI, alprenolol and nitroglycerin, in 30 patients (150 electroconvulsive therapy trials). Changes in cerebral blood flow velocity were measured by transcranial Doppler sonography of the right middle cerebral artery from the start of anesthesia to 10 min after the electrical shock.Results: Administration of a Ca2+ antagonist, nicardipine, or prostaglandin EI did not alter the augmented cerebral blood flow velocity after the seizure. However, a ß-adrenergic blocking agent, alprenolol (P<0.05) or nitroglycerin (P<0.01) partially inhibited the increase in cerebral blood flow velocity. Maximal blood flow velocity was 133% larger than the pre-anesthesia value in the control group, 109% in the nicardipine group, 113% in the prostaglandin EI group, 72% in the alprenolol group, and 45% in the nitroglycerin group, respectively. The increase in cerebral blood flow velocity after electrically induced seizure was independent of systemic blood pressure. Internal jugular venous saturation (SjO2) was increased, and difference in arterial and venous concentrations of lactate was not altered in all groups.Conclusions: Cerebral hemodynamics is altered by ECT, even when systemic hemodynamics are stabilized by antihypertensive medication. Although the effects of antihypertensive medicine on cerebral hemodynamics are variable, systemic blood pressure control by these agents does not induce cerebral ischemia after ECT.RésuméObjectif: Différentes thérapies antihypertensives ont été proposées comme moyen de prévention des réponses hyperdynamiques généralisées à la suite d’électrochocs. Dans la présente étude, on a analysé les effets de médicaments antihypertenseurs sur la circulation cérébrale.Méthode: La pression sanguine générale a été contrôlée par différents médicaments antihypertenseurs, la nicardipine, la prostaglandine El, l’alprénolol et la nitroglycérine, chez 30 patients lors de 150 essais d’électrochocs. Les changements de vitesse circulatoire cérébrale ont été mesurés par échographie Doppler transcrânienne de l’artère cérébrale moyenne droite, du début de l’anesthésie jusqu’à 10 min après l’électrochoc.Résultats: L’administration d’un antagoniste de Ca2+, la nicardipine, ou la prostaglandine El n’ont pas modifié la vitesse circulatoire cérébrale augmentée après les convulsions. Toutefois, un agent ß-bloquant, l’alprénolol (P<0,05) ou la nitroglycérine (P<0,01) ont partiellement inhibé l’augmentation de vitesse circulatoire cérébrale. La vitesse circulatoire maximale a été 133 % de la valeur préanesthésique mesurée dans le groupe témoin, de 109 % dans le groupe nicardipine, de 113 % dans le groupe prostaglandine El, de 72 % dans le groupe alprénolol et de 45 % dans le groupe nitroglycérine, respectivement. L’augmentation de la vitesse circulatoire cérébrale à la suite d’électrochocs a été indépendante de la pression sanguine générale. La saturation en oxygène de la veine jugulaire interne (SjO2) a été augmentée et les différences de concentration artérielle et veineuse de lactate n’ont pas été modifiées, dans aucun groupe.Conclusion: L’hémodynamie cérébrale est modifiée par l’électrochoc, même quand la stabilité de l’hémodynamie générale est conservée par une médication antihypertensive. Quoique les effets des antihypertenseurs sur l’hémodynamie cérébrale soient variables, la pression sanguine contrôlée par ces médicaments n’induit pas d’ischémie cérébrale après l’électrochoc.

Selective inducible nitric oxide inhibition can restore hemodynamics, but does not improve neurological dysfunction in experimentally-induced septic shock in rats.

In this study, we evaluated the time course of changes in inducible nitric oxide synthase (iNOS) in the brain by using the rat model of sepsis induced by cecal ligation and puncture (CLP) and examined whether selective iNOS inhibition can prevent the hemodynamic and neurological changes induced by sepsis. Male Wistar rats were randomly divided into four groups: control, sham, CLP, and CLP + the selective iNOS inhibitor l-N 6-(1-iminoethyl)-lysine (l-NIL). Septic shock was induced in the rats by CLP under pentobarbital anesthesia, and then we measured hemodynamic variables, neurological indicators, blood gases, plasma levels of nitrate/nitrite (an indicator of the biosynthesis of NO), and brain iNOS activity and nitrotyrosine levels after 1, 6, 12, and 24 h. Plasma nitrite was increased at 12 and 24 h in the CLP group. The activity of iNOS in the brain was increased at 12 and 24 h after CLP (at 12 h: control, 0.3 ± 0.05; sham, 0.3 ± 0.1; CLP, 1.3 ± 0.08*; CLP + l-NIL, 0.33 ± 0.1 fmol · mg−1 · min−1; at 24 h: control, 0.27 ± 0.08; sham, 0.31 ± 0.1; CLP, 1.0 ± 0.3*; CLP + l-NIL, 0.34 ± 0.1 fmol · mg−1 · min−1; mean ± sd; *P < 0.05). Brain nitrotyrosine was increased at 24 h after CLP (at 24 h: control, 6.7 ± 0.4; sham, 6.7 ± 0.5; CLP, 11.2 ± 2.8*; CLP + l-NIL, 7.52 ± 0.5 densitometric units; means ± sd; *P < 0.01). In contrast, in both the CLP and CLP + l-NIL groups, the consciousness reflex was significantly decreased at 24 h after CLP. Selective iNOS inhibition restored the hemodynamic changes induced by sepsis but could not improve neurological dysfunction.

Slow rewarming improves jugular venous oxygen saturation during rewarming

Background: There have been many studies regarding the etiology of postoperative cognitive dysfunction after coronary artery bypass graft (CABG) surgery. Although its etiology remains unresolved, one possible factor related to postoperative cognitive dysfunction is a reduced internal jugular venous oxygen hemoglobin saturation (SjvO2) during the rewarming period. The purpose of this study was to examine the effect of rewarming rates on SjvO2 during rewarming.

Impairment of hepatosplanchnic oxygenation and increase of serum hyaluronate during normothermic and mild hypothermic cardiopulmonary bypass

Hepatic sinusoidal endothelial cells (SECs) are more vulnerable to hypoxia or hypothermia than hepatocytes. To test the hypothesis that hepatic venous desaturation during cardiopulmonary bypass (CPB) leads to impairment of SEC function, we studied the plasma kinetics of endogenous hyaluronate (HA), a sensitive indicator of SEC function, and hepatosplanchnic oxygenation during and after CPB. Twenty-five consecutive patients scheduled for elective coronary artery bypass graft surgery, who underwent normothermic (>35°C;n = 15) or mild hypothermic (32°C;n = 10) CPB participated in this study. A hepatic venous catheter was inserted into each patient to monitor hepatosplanchnic oxygenation and serum levels of HA concentration. Hepatic venous oxygen saturation decreased essentially to a similar degree during normothermic and mild hypothermic CPB. Hepatosplanchnic oxygen consumption and extraction increased during normothermic (P < 0.05), but not mild hypothermic, CPB. Both arterial and hepatic venous HA concentrations showed threefold increases during and after CPB in both groups. A positive correlation was found between hepatosplanchnic oxygen consumption and arterial HA concentrations during CPB, suggesting a role of changes in hepatosplanchnic oxygen metabolism in the mechanisms of increases in serum HA concentrations. The failure of the liver to increase HA extraction to a great degree suggests that a functional impairment of the SEC may contribute to the observed increase of serum HA.

Anesthetic considerations in diabetic patients. Part I: preoperative considerations of patients with diabetes mellitus

Diabetes mellitus is an increasingly common disease that affects people of all ages, resulting in significant morbidity and mortality. Diabetic patients require perioperative care more frequently than their nondiabetic counterparts. The major risk factors for diabetics undergoing surgery are the associated end-organ diseases: cardiovascular disease, autonomic neuropathy, joint collagen tissue, and immune deficiency. Physicians need to pay extra attention to preoperative and preprocedure evaluation and treatment of these diseases to ensure optimal perioperative management.