Kimitoshi Nishiwaki

Differential effects of ketamine and midazolam on heart rate variability

Alterations in autonomic activity caused by anaesthesia can be assessed by spectral analysis of heart rate variability (HRV). This study examined the effects of ketamine and midazolam on HRV. Thirty patients of ASA PS 1 were studied. Fifteen were given ketamine (2 mg · kg−1) and 15 received midazolam (0.3 mg · kg−1), m The RR intervals of ECG were measured before and after induction of anaesthesia for ten minutes during spontaneous respiration. Power spectral density of the data was computed using fast Fourier transform. The spectral peaks within each measurement were calculated: low frequency area (LF, 0.04–0.15 Hz), high frequency area (HF, 0.15–0.5 Hz), and total power (TP, 0.04–0.5 Hz). Normalized unit power was derived as follows: low frequency area (nuLF): LF/ TP × 100%, high frequency area (nuHF): HF/TP × 100%. Both ketamine and midazolam caused reductions in all measurements of HRV power (P < 0.05). However, ketamine increased nuLF from 64 ± 14% to 75 ± 13% (P < 0.05) and decreased nuHF from 36 ± 14% to 25 ± 13% (P < 0.05), while midazolam decreased nuLF from 66 ± 15% to 54 ± 14% (P < 0.05) and increased nuHF from 34 ± 15% to 46 ± 14% (P < 0.05). These results documented that both ketamine and midazolam reduced the total power and all frequency components of power in spite of their opposing effects on autonomic nervous activity. However, normalized unit power showed the expected sympathetic activation with ketamine and sympathetic depression with midazolam since ketamine increased nuLFand midazolam decreased nuLF.RésuméIl est possible de mesurer l’activité autonome initiée par l’anesthésie au moyen de l’analyse spectrale des fluctuations de la fréquence cardiaque (FFC). Cette étude recherche les effets de la kétamine et du midazolam sur les FFC. Trente patients ASA PS I font partie de l’étude. Quinze ont reçu de la kétamine (2 mg · kg−1) et quinze du midazolam (0,3 mg · kg−1) iv. Les intervalles RR ont été mesurés à l’ECG avant et après l’induction de l’anesthésie pendant dix minutes de respiration spontanée. La densité de la puissance spectrale des données a été calculée après transformation rapide sur une échelle de Fourier. Les pointes spectrales de chaque mesure ont été calculées: zone de basse fréquence (LF, 0.04–0,15 Hz), zone de haute fréquence (HF, 0,15–0.5 Hz) et puissance totale (TP, 0,04–0,5 Hz). L’unité de puissance normalisée a été dérivee comme suit: zone de basse fréquence (nuLF): LF/TP × 100%, zone de haute fréquence (nuHF): HF/TP × 100% La kétamine et le midazolam provoquent des réductions de toutes les mesures de puissance des FFC (P < 0,05). Cependant la kétamine a augmenté nuLF de 64 ± 14% à 75 ± 13% (P < 0,05) et a diminue nuHF de 36 ± 14% à 25 ± 13% (P < 0,05), alors que le midazolam a diminué nuLF de 66 ± 14% à 54 ± 14% (P < 0,05) et a augmenté nuHF de 34 ± 15% à 46 ± 14% (P < 0,05). Ces résultats montrent que la kétamine et le diazépam réduisent tous deux la puissance totale et toutes les composantes fréquentielles de la puissance malgré leurs effets opposés sur l’activité nerveuse autonome. Cependant, l’unité de puissance normalisée a montré, comme on s’y attendait, l’activation sympathique par la kétamine et la dépression sympathique par le midazolam étant donné que la kétamine augmentait nuLF et que le midazolam diminuait nuLF.

Opposing effects of isoflurane and sevoflurane on neurogenic pulmonary edema development in an animal model.

Background:The current study was undertaken to investigate the effects of pretreatment with isoflurane and sevoflurane on the development of neurogenic pulmonary edema in an animal model. Methods:Rats were exposed to room air (control), 1.5% isoflurane, or 2.5% sevoflurane for 4 h. They were then anesthetized with intraperitoneal injections of pentobarbital sodium, and fibrinogen and thrombin were injected into the cisterna magna to induce neurogenic pulmonary edema. Results:Consecutive injections of fibrinogen and thrombin caused increases in blood pressure, with the peak values obtained in the isoflurane and sevoflurane groups being lower than the control values. The incidence of significant neurogenic pulmonary edema was 58%, 100%, and 8% in the control, isoflurane, and sevoflurane groups, respectively. The lung water ratio, an index of severity of edema, was 4.86 ± 0.78, 6.15 ± 0.64, and 4.40 ± 0.32 in the control, isoflurane, and sevoflurane groups, respectively. Furthermore, immunohistochemical staining for vascular endothelial growth factor demonstrated an increase of expression in the rat lungs exposed to isoflurane. Treatment with an anti–vascular endothelial growth factor antibody during exposure to isoflurane completely inhibited the effect of isoflurane to promote neurogenic pulmonary edema in this model. Conclusion:Exposure to 1.5% isoflurane enhances the development of neurogenic pulmonary edema development in this animal model, most likely via release of vascular endothelial growth factor from bronchial epithelial cells, an effect not observed with sevoflurane.

Role of neuropeptide Y and its receptor subtypes in neurogenic pulmonary edema

The effect of neuropeptide Y on the number of perivascular carbon deposits, assessed as a measure of lung vascular permeability, was examined in isolated perfused lung preparations of rats. The number of carbon particle deposits after bronchial application of neuropeptide Y was increased in a dose-dependent manner. In the presence of a beta-adrenoceptor antagonist, norepinephrine augmented the effects of neuropeptide Y. Peptide YY, an analog of neuropeptide Y, demonstrated a much lower potency for increasing the number of carbon deposits, and neuropeptide Y-(18-36), which elicits a weak antagonist action on the neuropeptide Y Y3 receptor, significantly decreased the neuropeptide Y-induced increase. Furthermore, examination of the influence of neuropeptide Y-(18-36) pretreatment on fibrin-induced neurogenic pulmonary edema, in rats, revealed a reduction of the protein concentration ratio of tracheal fluid to serum. Therefore, we conclude that neuropeptide Y may elevate vascular permeability in the pulmonary circulation, conceivably through the neuropeptide Y Y3 receptor, and that neuropeptide Y may in fact play a physiological role even in the in-situ pulmonary circulation.

Pretreatment with Topical 60% Lidocaine Tape Reduces Pain on Injection of Propofol

We determined whether pretreatment with topical 60% lidocaine tape reduced the incidence of pain on injection of propofol compared with mixing intravenous lidocaine with propofol.In a randomized, double-blind trial, 90 patients were allocated to one of three groups: pretreatment with a bioocclusive dressing and administration of a premixed solution of propofol 180 mg and 2 mL of normal saline (Group A); pretreatment with 60% lidocaine tape and a premixed solution of propofol and normal saline (Group B); or pretreatment with a bioocclusive dressing and a premixed solution of propofol 180 mg and lidocaine 40 mg (Group C). The incidences of pain in Groups A, B, and C were 86.7%, 33.4%, and 20%, respectively. Group B and Group C had a significantly lower incidence of pain than Group A. There was no significant difference in the incidence of pain between Group B and Group C. There was no significant difference in the distribution of site of pain on injection of propofol among the three groups. Pretreatment with topical 60% lidocaine tape reduced the incidence of pain on injection of propofol similar to that of intravenous lidocaine mixed with propofol. Implications: Pretreatment with topical 60% lidocaine tape reduces the pain associated with injection of propofol, a frequently used intravenous anesthetic. This approach should increase patient comfort during induction of anesthesia. (Anesth Analg 1997;85:672-4)

A greater decrease in blood pressure after spinal anaesthesia in patients with low entropy of the RR interval

Background:  The objective of this study was to determine whether pre‐operative heart rate variability (HRV) estimated using the newly developed MemCalc method predicts hypotension after spinal anaesthesia (SA).

Heart rate variability during massive hemorrhage and progressive hemorrhagic shock in dogs

Purpose: To investigate the sequential changes in heart rate (HR), autonomic nervous activity presented by the spectral analysis of heart rate variability (HRV), hemodynamics and metabolism during massive hemorrhage and progressive hemorrhagic shock in dogs.Methods: Twelve dogs were subjected to acute massive hemorrhage until mean arterial pressure (MAP) reached 50 mmHg. Then bleeding was stopped and they were allowed to reach a plateau phase. They were divided, post hoc, into bradycardic or tachycardic groups according to their HR response to the acute massive hemorrhage. After reaching a plateau phase, the dogs were further bled to keep their MAP around 50 mmHg (progressive hemorrhagic shock). Their heart rate power spectra were quantified into low-frequency (LF) (0.04–0.15 Hz) and high-frequency (HF) (0.15–0.4 Hz) components.Results: In the bradycardic group, both LF and HF increased after massive hemorrhage, but during progressive hemorrhagic shock these components decreased while HR increased. In the tachycardic group, LF increased after massive hemorrhage, but during progressive hemorrhagic shock LF decreased with continuous suppression of HF.Conclusion: Massive hemorrhage caused two types of HR response: bradycardia and tachycardia. The HRV profile showed differential autonomic characteristics, and could be a valuable tool in assessing various degrees of hemorrhagic shock.RésuméObjectif: Examiner les changements de fréquence cardiaque (FC), l’activité nerveuse autonome selon l’analyse spectrale de la variabilité de la fréquence cardiaque (VFC), l’hémodynamie et le métabolisme pendant une hémorragie massive et un choc hémorragique progressif, chez des chiens.Méthode: Douze chiens ont été soumis à une hémorragie aiguë massive jusqu’à ce que la tension artérielle moyenne (TAM) atteigne 50 mmHg. Puis, on a arrêté le saignement et laissé la pression parvenir à un plateau. On a, en conséquence, réparti les animaux en groupe bradycardie ou tachycardie selon le compotement de la FC pendant l’hémorragie aiguë massive. Un plateau une fois atteint, les chiens ons subi une autre hémorragie pour amener leur TAM autour de 50 mmHg (choc hémorragique progressif). Le spectre de la puissance de la fréquence cardiaque a été quantifié en composantes de basses fréquences (BF) (0,04–0,15 Hz) et de hautes fréquences (HF) (0,15–0,4 Hz).Résultats: Dans le groupe bradycardie, les BF et HF ont augmenté après l’hémorragie massive, mais lors du choc hémorragique progressif, ces composantes ont diminué pendant que la FC augmentait. Dans le groupe tachycardie, les BF ont augmenté après l’hémorragie massive, mais lors du choc, elles ont baissé en même temps que survenait la suppression continue des HF.Conclusion: L’hémorragie massive a causé deux types de réaction de la FC: la bradycardie et la tachycardie. Le profil de VFC a affiché des caractéristiques autonomes différentielles, ce qui en fait un outil valable pour évaluer différents degrés de choc hémorragique.

Recovery of heart rate variability profile in patients after coronary artery surgery

We examined the different characteristics of heart rate variability (HRV) to define the time course of HRV profile after coronary artery surgery (CAS).Spectral analysis of HRV was performed on a 512-s segment of R-R intervals of the electrocardiogram on the preoperative day and on Postoperative Days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28. Power spectral area was divided into low (0.04-0.15 Hz; LF)-and high (0.15-0.5 Hz; HF)-frequency components. Fractal slope and sympathovagal slope of 1/f characteristics of HRV were determined in two different frequency ranges (from 0.01 to 0.15 Hz and from 0.01 to 0.5 Hz, respectively). Three recovery profiles of HRV were identified. Early HRV recovery profiles (Postoperative Days 1-6) included reduction in LF, HF, and sympathovagal slope, as well as an increase in fractal slope. Subsequent HRV recovery profiles (Postoperative Days 7-21) revealed reductions in LF, HF, and sympathovagal slope. Fractal slope became normal. Later HRV recovery profiles (Postoperative Day 28) demonstrated that all spectral components of HRV remained reduced, but sympathovagal and fractal slopes became normal. These changes in the HRV profile after CAS suggest significant postoperative alterations in cardiovascular homeostasis with significant but incomplete recovery during the first 28 postoperative days. Implications: Heart rate variability reflects normal neural regulation of cardiac function. This variability remains depressed as long as 28 days after coronary artery bypass surgery, but can recover as early as 1 wk postoperatively. Despite implied loss of normal neural regulation of cardiac function, a specific correlation between depressed heart rate variability and outcomes was not performed. (Anesth Analg 1997;85:713-8)

Heart rate variability and arterial blood pressure variability show different characteristic changes during hemorrhage in isoflurane-anesthetized, mechanically ventilated dogs.

UNLABELLED: We assessed the changes in heart rate variability (HRV) and blood pressure variability (BPV) as indices of autonomic nervous system and volume status during hemorrhage in isoflurane-anesthetized, mechanically ventilated dogs. Nine dogs were used. They were sequentially subjected to withdrawal of 30% estimated blood volume and graded isoflurane inhalation of 1% and 2% followed by discontinuation of isoflurane and retransfusion. The power spectra of HRV and BPV were computed using the fast Fourier transformation, and were quantified by determining the areas of the spectrum in two component widths: low-frequency component (LF) (0.04-0.15 Hz) and high-frequency component (HF) (0.15-0.4 Hz). During hemorrhage and isoflurane anesthesia, both HRV-LF and HRV-HF were decreased and plateaued at the smaller concentration of isoflurane, whereas BPV-LF decreased concentration-dependently. BPV-HF showed a completely different response and increased significantly during 2% isoflurane. We speculate that HRV and BPV-LF would be affected by the autonomic nervous activity, whereas BPV-HF would depend on relative/absolute change in circulating blood volume. IMPLICATIONS: Power spectra of heart rate variability (HRV) and blood pressure variability (BPV) were computed using the fast Fourier transformation. The HRV and BPV showed their differential characteristics during hemorrhage, isoflurane anesthesia, and retransfusion, and would help to assess changes in autonomic nervous system and preload under mechanical ventilation.

Preoperative Ultra Short-Term Entropy Predicts Arterial Blood Pressure Fluctuation During the Induction of Anesthesia

BACKGROUND:In this study, we sought to determine whether the preoperative nonlinear index of heart rate variability, ultra short-term entropy (UsEn), could predict cardiovascular responses to the induction of general anesthesia. METHODS:UsEn was estimated by a linearized version of the nonlinear least squares method combined with the maximum entropy spectral analysis method (MemCalc method). Preoperative UsEn of 46 patients (ASA PS 1 or 2, aged 40–60 yr) without a history of hypertension was evaluated using the MemCalc method. Patients were assigned to two groups according to preoperative UsEn (Group LOW; UsEn <45, Group HIGH; UsEn ≥45). Anesthesia was induced with propofol, fentanyl and vecuronium bromide and endotracheal intubation was performed. Hemodynamic fluctuations during the induction of anesthesia were recorded and compared between the two groups. RESULTS:It was found that arterial blood pressure fluctuations during the induction of anesthesia were significantly greater in patients with a low UsEn. CONCLUSION:UsEn could predict arterial blood pressure fluctuations during the induction of anesthesia.

No changes in cerebrospinal fluid levels of nitrite, nitrate and cyclic GMP with aging

SummaryNitric oxide (NO) is a free radical gas that plays a role in various signal transduction processes. NO has been proposed to have a function in the mechanism of synaptic plasticity, including long-term potentiation and memory formation in vivo. Because a failure in synaptic plasticity is considered to be involved in aging-associated brain dysfunction, NO production in the brain may be altered by aging. In the present study, we measured the levels of NO metabolites, nitrite and nitrate, and cyclic GMP in the cerebrospinal fluid (CSF) of human subjects without neurological or psychiatric disorders. There were no age-related changes in the CSF levels of either nitrite, nitrate or cyclic GMP. These results suggest that NO production in the brain may be maintained during the aging process.