Tetsuhiro Sakai

Haemodynamic and electroencephalograph responses to intubation during induction with propofol or propofol/fentanyl

PurposeTo observe the changes in EEG bispectral index (BIS), 95% spectral edge frequency (95% SEF) and median frequency (MF) with haemodynamic changes to intubation during induction with propofol or propofol and 2 μg· kg−1 fentanyliv.MethodsTwenty four ASA 1–11 patients were randomized to receive either propofol infusion preceded by normal saline (group P, n= 12) or propofol preceded by 2 μg· kg−1 fentanyl (group PF, n= 12). Intubation was performed five minutes after maintenance of BIS within 45 ± 5. EEG and haemodynamic variables were recorded at before induction, and before and after intubation.ResultsHaemodynamic responses to intubation were greater in group P than in group PF (P < 0.05). Postintubation SBP, DBP and HR increased, compared with preinduction values, more in group P than in group PF Postintubation BIS values increased from 45.5 ± 3.5 and 44.2 ± 4.1 to 51.1 ± 4.1 and 50.9 ± 5.3 in groups P and PF, respectively, compared with preintubation values. The BIS values were not different between treatment groups before and after intubation, and 95% SEF and MF values did not increase after intubation.ConclusionFentanyl, 2 μg· kg−1iv, blunted the haemodynamic responses to intubation, but failed to attenuate the arousal of cerebral cortical activity. The different haemodynamic responses postintubation but similar BIS and 95% SEF changes in the two groups suggest that BIS or 95% SEF cannot predict the haemodynamic responses to intubation during anaesthesia induction with propofol and fentanyl.RésuméObjectifObserver les altérations de l’index ÉEG bispectral (BIS), sur la fréquence spectrale de marge (95% SEF) et la fréquence moyenne (FM) causées par les changements hémodynamiques de l’intubation pendant l’induction au propofol ou au propofol associé au fentanyl 2 μg· kg−1iv.MéthodesVingt-quatre patients ASA 1–11 ont reçu aléatoirement soit une perfusion de propofol précédée de sol. phys. (groupe P, n = 12) ou de propofol précédé de fentanyl 2 μg· kg−1 (groupe PF, n = 12). On intubait cinq minutes après la stabilisation du BIS entre 45 ± 5. L’ÉEg et les variables hémodynamiques étaient enregistrées avant l’induction, et avant et après l’intubation.RésultatsLes réponses hémodynamiques à l’intubation étaient plus importantes dans le groupe P que dans le groupe PF (P< 0,05). Après l’intubation, la pression artérielle systolique et diastolique et la Fc augmentaient comparativement aux valeurs de préinduction, mais plus dans le groupe P que dans le groupe PF Après l’intubation, les valeurs du BIS augmentaient de 45 ± 3,5 à 51 ± 4.1 dans le groupe P et de 44 ± 4,1 à 50,9 ± 5,3 dans les groupes PF comparativement aux valeurs précédant l’intubation ; les valeurs SEF 95% et MF n’augmentaient pas après l’extubation.ConclusionLe fentanyl 2 μg· kg−1iv atténue les réponses hémodynamiques à l’intubation mais ne parvient pas à atténuer l’éveil de l’activité corticale cérébrale. La différence des réponses hémodynamiques postintubation mais la similarité des changements de BIS et de SEF95% dans les deux groupes suggèrent que BIS et SEF 95% ne peuvent prédire les réponses hémodynamique à l’intubation pendant l’induction de l’anesthésie au propofol et au fentanyl.

Systemically administered α-melanocyte-stimulating peptides inhibit NF-κB activation in experimental brain inflammation

Abstract The neuropeptide α-melanocyte-stimulating hormone (α-MSH) and its C-terminal tripeptide α-MSH11-13 modulate production of proinflammatory cytokines and inhibit inflammation. We examined whether systemic α-MSH and α-MSH11-13 inhibit activation of the nuclear transcription factor, nuclear factor kappa B (NF-κB), a factor that is essential to expression of proinflammatory cytokines, in experimental murine brain inflammation induced by lipopolysaccharide. Electrophoretic mobility shift assays of nuclear extracts demonstrated that parenteral α-MSH inhibited NF-κB activation. Western blot analysis revealed that this inhibition was linked to α-MSH-induced preservation of expression of IκBα protein in the brain. The effects of α-MSH on NF-κB and IκBα were paralleled by pretreatment with α-MSH11-13. Similar effects of the two peptides were observed in mice with nonfunctional melanocortin 1 receptors (MC1R), ruling out the possibility that this receptor subtype is essential to the influence on NF-κB. These findings indicate that α-MSH peptides given systemically can inhibit NF-κB activation induced in acute brain inflammation even in the absence of MC1R.

Inhibition of peripheral NF-κB activation by central action of α-melanocyte-stimulating hormone

Abstract With the rise in the field of neuroimmunomodulation research, there is increased recognition of the influence of the nervous system and neuropeptides in peripheral disease. The neuropeptide α-melanocyte-stimulating hormone (α-MSH) is a neuroimmunomodulatory agent that modulates production of proinflammatory cytokines and inhibits peripheral inflammation via actions on CNS receptors. We examined whether central α-MSH operates by inhibiting activation of the nuclear factor kappa B (NF-κB) that is essential to the expression of proinflammatory cytokines and development of inflammation in the periphery. Electrophoretic mobility shift assays of nuclear extracts from the murine foot pad injected with TNF-α demonstrated that centrally administered α-MSH does inhibit NF-κB activation. Western blot analysis revealed that this inhibition was linked to central α-MSH-induced preservation of expression of IκBα protein in the peripheral tissue. The NF-κB and IκBα effects were inhibited in mice with spinal cord transection. Intraperitoneal (ip) injection of the nonspecific β-adrenergic receptor blocker propranolol, and of a specific β 2 -adrenergic receptor antagonist, likewise prevented these effects of central α-MSH; blockade of cholinergic, α-adrenergic, or β 1 -adrenergic receptors did not. Centrally administered α-MSH inhibited peripheral NF-κB activation and IκBα degradation even in mice with nonfunctional melanocortin 1 receptors (MC1R). These findings indicate that α-MSH can act centrally to inhibit NF-κB activation in peripheral acute inflammation via a descending neural pathway. The pathway involves β 2 -adrenergic receptors, but does not require activation of MC1R within the brain.

Ketamine suppresses endotoxin-induced NF-κB expression

Purpose: Ketamine reduces endotoxin-induced production of proinflammatory cytokines, including tumour necrosis factor- α (TNF), in several types of inflammatory cells, including monocytes and macrophages. Transcription of the genes that encode production of these proinflammatory cytokines is regulated by nuclear factor-kappa B (NF-κB). Cytoplasmic B protein is activated by endotoxin (LPS) as well as by TNF, allowing B protein to migrate into the cell nucleus to activate gene transcription for these inflammatory mediators. Because NF-κB is likely involved in brain injury and inflammatory neurodegenerative disease, such as multiple sclerosis, we examined whether ketamine inhibits LPS-induced activation of NF-κB in human glioma cellsin vitro and intact mouse brain cellsin vivo.Methods: Endotoxin-induced NF-κB expression in both the human glioma cellsin vitro and the intact mouse brain cellsin vivo was determined by electrophoretic mobility shift assays (EMSA) of nuclear extracts and measurement of NF-κB expression by densitometry. Endotoxin was injected intracerebroventricularlyin vivo and intact brain was harvested. Klenow fragment labeling was used to identify NF-κB protein for both thein vivo andvitro experiments.Results: Endotoxin treatment increased NF-κB expression (P<0.05) bothin vivo andvitro compared with control (untretaed) cells. Ketamine suppressed endotoxin-induced neuronal NF-κB activation in a dose-dependent manner (P<0.05, except for the 10−5M concentrationin vitro) bothin vivo andvitro.Conclusion: Ketamine inhibits endotoxin-induced NF-κB expression in brain cellsin vivo andvitro and it is suggested that this may have implications in the neuroprotective effects of ketamine reported by other investigators.RésuméObjectif: La kétamine réduit la production de cytokines pro-inflammatoires induite par endotoxine, y compris le facteur nécrosant des tumeurs (TNF), dans certains types de cellules inflammatoires comprenant les monocytes et les macrophages. La transcription des gènes qui encodent la production de ces cytokines pro-inflammatoires est réglée par le facteur-kappa B nucléaire (NF-6B). La protéine cytoplasmique 6B est activée par l’endotoxine (LPS) et par le TNF et peut ainsi migrer dans le noyau cellulaire et activer la transcription génique pour ces médiateurs de l’inflammation. Comme le NF-6B participe probablement aux lésions cérébrales et aux maladies inflammatoires neurodégénératives, dont la sclérose en plaques, notre but était de savoir si la kétamine inhibe l’activation de NF-6B induit par LPS dans des cellules de gliome humainin vitro et dans des cellules cérébrales intactes de sourisin vivo.Méthode: L’expression du NF-6B induite par endotoxine dans les cellules humainesin vitro et dans les cellules de sourisin vivo a été déterminée par une étude de retardement de la mobilité électrophorétique (ERME) d’extraits nucléaires et la mesure de l’expression du NF-6B a été faite par densitométrie. L’endotoxine a été injectée dans les ventricules cérébrauxin vivo et du tissu cérébral intact a été prélevé. Le marquage de fragments de Klenow a été utilisé pour identifier la protéine du NF-6B des deux expériencesin vivo etvitro.Résultats: Le traitement avec l’endotoxine a augmenté l’expression du NF-6B (P<0,05) des cellulesin vivo etin vitro comparées aux cellules témoin (non traitées). La kétamine a supprimé l’activation neuronale de NF-6B induite par endotoxine d’une façon dose-dépendante (P<0,05, sauf pour une concentration de 10−5Min vitro) des cellulesin vivo etin vitro.Conclusion: La kétamine inhibe l’expression de NF-6B induite par endotoxine dans des cellules cérébralesin vivo etin vitro et on croit que cela pourrait contribuer aux effets neuroprotecteurs de la kétamine dont parlent d’autres chercheurs.

Motor and Sensory Disability Has a Strong Relationship to Induction Dose of Thiopental in Patients with the Hypertropic Variety of Charcot-Marie-Tooth Syndrome

In a prospective study, we determined the anesthetic induction dose of thiopental and the clinical variables influencing the appropriate induction dose of thiopental in 20 patients with the hypertrophic variety of Charcot-Marie-Tooth syndrome (CMT). As controls we chose 50 patients without CMT. Motor disturbance was evaluated in terms of muscle weakness of the distal lower and upper extremities. We examined sensory disturbance by evaluating loss of sensation in the index finger and great toe. The preinduction cardiac output was measured by echocardiography. Anesthesia was induced with repeated injections of 50 mg thiopental. The minimum induction dose of thiopental (MID) was confirmed when the eyelash reflex ceased. We maintained anesthesia with enflurane and nitrous oxide. The 95% confidence interval of the MID in patients used as the controls was 2.5-4.9 mg/kg. The MID in 11 patients with CMT was less than 2.5 mg/kg. MIDs in the patients with CMT were significantly smaller than those of the control patients (P < 0.0001). Also we found a strong relationship between the MID and the severity of both motor and sensory disturbances (P = 0.003 and 0.002, respectively). There was no relationship between the MID and other clinical variables, such as age, gender, inherited type, body weight, and preinduction cardiac output. Because delay in the recovery from anesthesia can be caused by an inappropriate dose of thiopental in CMT patients in whom motor and sensory function is seriously impaired, the dose of thiopental probably should be reduced and based on the individual patients response. (Anesth Analg 1996;82:182-6)

The interaction between fentanyl and propofol during emergence from anesthesia: monitoring with the EEG-Bispectral index.

STUDY OBJECTIVE To investigate the effect of different plasma levels of fentanyl on the concentration of propofol and the Bispectral Index (BIS) required for patients to regain consciousness and orientation following surgery. DESIGN Prospective, open-label study. SETTING Operating room of a university hospital. PATIENTS 28 patients, aging 20 to 50 years, scheduled for elective, 1- to 4-hour surgeries under general anesthesia. INTERVENTIONS BIS was continuously monitored from bifrontal montage (At1-Fpz and At2-Fpz) using an Aspect A-1,050 EEG system (Aspect, Natick, MA). Anesthesia was induced with bolus injections of fentanyl 2 microg/kg and propofol 2 mg/kg, and maintained with intermittent injections of fentanyl and constant infusion of propofol. Propofol infusion was stopped at the end of surgery. MEASUREMENTS Consciousness and orientation were assessed as clinical endpoints once every 2 minutes following the end of the surgery. Blood samples were extracted for plasma propofol and fentanyl concentrations (PCp and FCp, respectively), and BIS values were recorded when patients regained consciousness and orientation. Patients were allocated to one of three groups depending on FCp on awakening: Group 1, FCp > 1 microg/L (n = 8); Group 2, FCp < 1 microg/L and >0.45 microg/L (n = 9); and Group 3, FCp < 0.45 microg/L (n = 11). PCp, BIS, recovery time, and other data were compared between the three groups. MAIN RESULTS Demographic values, duration of surgery, and consumption of propofol and fentanyl were not different between the three groups. Group 3 patients regained consciousness with significantly higher propofol concentration (mean PCp = 3.2 mg/L) compared with those in Groups 1 and 2 (p < 0.05). However, the BIS values at both recovery endpoints were not different among the three groups. CONCLUSIONS The plasma levels of fentanyl affect the concentrations of propofol required for patients to regain consciousness. The BIS values for wakefulness are unaltered at the different combinations of propofol and fentanyl concentrations. Thus, the BIS appears to be a useful and consistent indicator for level of consciousness during emergence from propofol/fentanyl intravenous anesthesia.

Perioperative measurements of interleukin-6 and α-melanocyte-stimulating hormone in cardiac transplant patients

Interleukin-6 (IL-6) and alpha-melanocyte-stimulating hormone (alpha MSH) are important modulators of the immunologic response to tissue injury and antigenic challenge. Serial changes in the plasma concentrations of these two peptides were measured in 12 patients undergoing heart transplantation. Tissue concentrations of IL-6 in atrial samples from both donor and recipient hearts were also compared. Plasma IL-6 concentration remained stable prior to cardiopulmonary bypass (CPB), initially decreased with the onset of CPB, and then increased significantly over control values at the end of CPB (180 +/- 40 v 53 +/- 60 pg/mL). Plasma IL-6 remained elevated for at least 60 minutes after CPB, and then it returned to control values by 24 hours postoperatively (67 +/- 9 pg/mL). Examination of IL-6 changes after CPB in 10 additional patients undergoing nontransplant cardiac surgery with CPB revealed a similar elevation in IL-6 at 60 minutes after CPB (290 +/- 76 pg/mL). However, IL-6 in the nontransplant group remained significantly elevated at 24 hours (138 +/- 42 pg/mL). These combined results suggest that CPB causes a marked increase in IL-6, and that implantation of a new heart in transplant patients does not augment this increase. The return of IL-6 to control values by 24 hours in the patients who have had transplants suggests that immunosuppression has an appreciable effect on IL-6 at this time. In contrast to IL-6, plasma alpha MSH never increased above control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in plasma atrial natriuretic peptide concentration during heart transplantation

Examination of changes in plasma atrial natriuretic peptide (ANP) concentrations during heart transplantation may provide important information about factors influencing plasma ANP in patients with severe heart failure. Serial changes in plasma ANP during heart transplantation, and atrial content of ANP in native and donor atria, were measured in 12 patients. Preoperative plasma ANP was elevated in all patients (387 +/- 77 pg/mL), whereas atrial content of ANP in native atria was reduced (0.36 +/- 0.082 micrograms/mg protein). Preoperative plasma ANP did not correlate with hemodynamics, but was negatively correlated with creatinine clearance (r = -0.76, P < .01). Intraoperative plasma ANP prior to transplantation was strongly correlated with intraoperative plasma ANP after transplantation (r = 0.84, P < .001). Although postoperative plasma ANP was reduced from preoperative plasma ANP by 75%, these two measurements were also significantly correlated (r = 0.70, P < .02). Postoperative plasma ANP was not correlated with hemodynamics, but was negatively correlated with both creatinine clearance (r = -0.65, P < .05) and content of ANP in the native atria (r = -0.75, P < .01). Multiple linear regression analysis suggested that up to 85% of the variability of early postoperative plasma ANP could be accounted for by the variability in these latter two parameters. The decrease in native atrial ANP content, in the context of elevated plasma ANP concentration, is consistent with prior animal studies suggesting that severe heart failure induces cellular adaptations favoring accelerated ANP synthesis and secretion (with resultant reduction in tissue content).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Management and Rigid Spine Syndrome

R igid spine syndrome (RSS) was first described by Dubowitz in 1965 (1). Fibrous shortening of the cervical extensor muscles is the main characteristic of the syndrome, which causes a marked limitation of the cervical spine flexion. Scoliosis, contracture of many joints, and myopathic changes in the skeletal muscles are also frequent complications, and most patients die of either respiratory failure or cardiomyopathy (2-5). Recently, we experienced a case in which local anesthesia was successfully used for the surgical procedure (release of the cervical ligaments) to maintain spontaneous respiration and avoid any airway troubles.

Nuclear factor-κB activation during anesthesia and surgery

Abstract Transcription of the genes for proinflammatory cytokines is regulated by nuclear factor kappa B (NF-κB) activation. Cardiopulmonary bypass (CPB) is characterized by a systemic endotoxemia demonstrated immediately following CPB institution followed by the systemic release of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and the interleukins (IL) 1, 6 and 8. However, the mechanism of the release of these proinflammatory cytokines remains to be determined. NF-κB is an inducible transcription factor implicated in activating various genes including those genes which encode for cytokines such as TNF, IL-1 and IL-6. The NF-κB protein is found in several cell types including inflammatory cells, for example peripheral blood monocytes, one of the cell types responsible for LPS-induced proinflammatory cytokine production. Therefore, we examined whether NF-κB is activated during CPB in order to define a mechanism of CPB-induced proinflammatory cytokine production and release.