Levobupivacaine-dextran mixture for transversus abdominis plane block and rectus sheath block in patients undergoing laparoscopic colectomy: a randomised controlled trial.

We performed a randomised controlled double-blinded study of patients having laparoscopic colectomy with bilateral transversus abdominis plane block plus rectus sheath block, comparing a control group receiving 80 ml levobupivacaine 0.2% in saline with a dextran group receiving 80 ml levobupivacaine 0.2% in 8% low-molecular weight dextran. Twenty-seven patients were studied in each group. The mean (SD) maximum plasma concentration of levobupivacaine in the control group (1410 (322) ng.ml(-1) ) was higher than the dextran group (1141 (287) ng.ml(-1) ; p = 0.004), and was reached more quickly (50.6 (30.2) min vs 73.2 (24.6) min; p = 0.006). The area under the plasma concentration-time curve from 0 min to 240 min in the control group (229,124 (87,254) ng.min.ml(-1) ) was larger than in the dextran group (172,484 (50,502) ng.min.ml(-1) ; p = 0.007). The median (IQR [range]) of the summated numerical pain rating score at rest during the first postoperative 24 h in the control group (16 (9-20 [3-31]) was higher than in the dextran group (8 (2-11 [0-18]); p = 0.0001). In this study, adding dextran to levobupivacaine decreased the risk of levobupivacaine toxicity while providing better analgesia.

Increased heart rate variability correlation between mother and child immediately pre-operation.

BACKGROUND: Maternal distress would correlate with the children's mental status, thereby influencing the activity of the autonomic nervous system (ANS) of the children and mothers. We hypothesized that pre-anesthetic maternal ANS activity, when approaching close to their children's operation time, would correlate with children's ANS activity, and that the values of heart rate variability (HRV) would correlate. METHODS: We calculated maternal and children's HRVs and analyzed the relationship between the two. A total of 24 pairs of mother and child were analyzed. Maternal and children's HRVs were recorded from the night before the child's surgery to the arrival to the operation room. RESULTS: The ratios of low-frequency components (LF) to high-frequency components (HF) (LF/HF ratio) of children's and maternal HRVs obtained during the immediate pre-operative period (06:00-08:00 hours) showed a significantly, positive correlation, but no correlation was found for the LF/HF ratios obtained during the pre-operative night. CONCLUSION: The LF/HF ratios of HRV immediately before surgery in children and mothers showed a significant positive correlation.

Halothane, an inhalation anesthetic, activates protein kinase C and superoxide generation by neutrophils.

The rate of superoxide generation of guinea pig intraperitoneal neutrophils by a chemotactic peptide or 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased by 2-bromo-2-chloro-1,1,1,-trifluoroethane (halothane), an inhalation anesthetic. This increase was inhibited by 1-(5-isoquinolinesulfonyl)methylpiperazine dihydrochloride (H-7), a specific inhibitor of Ca2+- and phospholipid-dependent protein kinase C (PKC). Halothane was found to significantly activate partially purified PKC. The activation required phosphatidylserine (PS) and Ca2+. Dioleoylglycerol- or TPA-activated PKC activity was further increased by halothane. The cytoplasmic proteins of guinea pig neutrophils phosphorylated by halothane-activated PKC were similar to those phosphorylated by PMA-activated PKC. The phosphorylation of a 48 kDa protein, a phosphorylated protein required for NADPH oxidase activation, was also increased by halothane. These data suggest that the increase of superoxide production by halothane is correlated with its activation of PKC.

Lidocaine inhibits priming and protein tyrosine phosphorylation of human peripheral neutrophils.

The addition of agents, such as tumor necrosis factor-alpha, to human peripheral neutrophils (HPPMN) induces priming, which enhances the receptor-mediated superoxide (O2-) generation and tyrosine phosphorylation of several HPPMN proteins. Lidocaine, a local anesthetic, inhibited both enhanced O2- generation and tyrosine phosphorylation of a 115 kDa protein in a concentration- and time-dependent manner. Lidocaine also inhibited protein kinase C sensitive O2- generation induced by phorbol myristate acetate, but not time dependently. Furthermore, lidocaine inhibited O2- generation by non-primed HPPMN induced by formylmethionyl-leucyl-phenylalanine, but this inhibition needed a higher concentration of lidocaine compared with that of primed HPPMN. These results suggest that lidocaine inhibits the priming step of neutrophil activation and that it is linked to the inhibition of tyrosine phosphorylation of a 115 kDa protein.

Halothane enhances the phosphorylation of H1 histone and rat brain cytoplasmic proteins by protein kinase C.

The effect of halothane, a typical volatile anesthetic, on the calcium- and phospholipid-dependent protein kinase (PKC), which is one of the key enzymes of membrane signal transduction, was examined. PKC was partially purified from the cerebral tissue of male Wistar rats. Halothane increased PKC-mediated phosphorylation of calf thymus H1 histone in the presence or absence of phorbol ester or diolein, and also increased phosphorylation of the rat brain cytosolic proteins (47 kDa and 80 kDa). A similar but slight increase in H1 histone phosphorylation was observed with isoflurane and enflurane, less lipid soluble volatile anesthetics. These findings suggest that halothane may increase PKC-mediated phosphorylation by the modification of phospholipid membrane and affect membrane signal transduction of the nerve cell under the anesthetic state.

Increased production of interleukin-10 by human blood monocytes stimulated with Mycobacterium avium-intracellulare complex.

Macrophages produce various cytokines in response to mycobacteria, including interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha). IL-10 has been shown to down-regulate numerous macrophage functions, including microbicidal activity against intracellular bacteria and parasites. IL-10 also inhibits interferon-gamma (IFN-gamma) production and antigen-specific proliferation of Th1 cells mediating immunologic resistance to mycobacterial infection. In contrast, TNF-alpha activates macrophages and may augment their mycobacterial activity. In this study, peripheral blood mononuclear cells (PBMC) or blood monocytes obtained from healthy tuberculin reactors were stimulated in vitro with heat-killed Mycobacterium tuberculosis or heat-killed M. avium-intracellulare complex (MAC) to produce IL-10 and TNF-alpha. We studied a total of 26 clinical isolates of M. tuberculosis and 28 isolates of MAC. MAC-stimulated PBMC and monocytes released significantly larger amounts of IL-10 than those cells stimulated with M. tuberculosis. However, there was no difference in induction of TNF-alpha production between MAC and M. tuberculosis. When TNF-activity was neutralized by the addition of anti-TNF-alpha mAb in culture, MAC still induced more IL-10 secretion than did M. tuberculosis. These findings suggest that increased production of IL-10 by MAC-stimulated monocytes may play a role in the intractable disease caused by these organisms.

Local anesthetics enhance nitric oxide production by human peripheral neutrophils.

Various neutrophil functions are suppressed by local anesthetics. We studied the effect of local anesthetics on nitric oxide (NO) generation in human peripheral neutrophils. Lidocaine and other local anesthetics stimulated NO generation in resting neutrophils. Canavanine, an NO synthase inhibitor, inhibited NO generation. Lidocaine and the other local anesthetics enhanced formylmethionyl-leucyl-phenylalanine (FMLP) or phorbol myristate acetate (PMA)-induced NO generation. These findings suggest that NO mediates various pharmacological effects of the local anesthetics on the host defense mechanism and the control of blood pressure.

Lidocaine inhibits stimulation-coupled responses of neutrophils and protein kinase C activity.

The effects of lidocaine, a local anesthetic, on various stimulation-coupled responses of neutrophils were studied. Superoxide generation, generation of chemiluminescence, depolarization of membrane potential and transitional increase in intracellular Ca2+ were inhibited by lidocaine in a concentration dependent manner. Lidocaine also inhibited Ca(2+)-activated phospholipid-dependent protein kinase (PKC) in the presence of various concentrations of Ca2+, phosphatidylserine and dioleoylglycerol. For the inhibition of all these stimulation-coupled responses, a similar order of the lidocaine concentration was needed. As in the case of dibucaine (Mori, T., Takai, Y., Minakuchi, R., Yu, B. and Nishizuka, Y., J. Biol. Chem. 255:8378-8380, 1980), lidocaine inhibited PKC activity in a manner competitive with phosphatidylserine. Lidocaine also inhibited the phosphorylation of 47 kDa neutrophil cytosplasmic protein, a phosphorylated protein required for NADPH oxidase activation. Thus, the cellular membrane phospholipid may be one of the target sites of lidocaine for the inhibitory action on the various stimulation-coupled responses of neutrophils, and these effects of lidocaine may correlate with its inhibitory action on PKC activity.

[Effect of lidocaine-epinephrine-dextran solution on the plasma epinephrine concentration during spinal surgery--how to avoid circulatory complications due to the use of epinephrine for hemostasis].

Epinephrine infiltrated for hemostasis may cause adverse effect on the circulatory system and the effect can be potentiated by surgical stimulation. Local infiltration of lidocaine-epinephrine-dextran solution (LED) at the surgical site is advantageous for this purpose since nerve blocking action of lidocaine attenuates surgical stimulation and dextran suppresses the transfer of injected epinephrine to the blood stream, thereby reducing the adverse effect of epinephrine. LED, however, could be injected accidentally into vessels. This is one of the important causes of raising the plasma epinephrine concentration to a dangerous level. The author believes that the following maneuvers are helpful to avoid the rise of plasma epinephrine concentration to a dangerous level; 1) injecting not more than 0.05 ml.kg-1 at a time, 2) monitoring the arterial pressure waves and ECG during the injection by use of a continuous recording device, and 3) halting the injection immediately whenever sudden changes in the arterial pressure and in the height of the T wave in ECG were observed. More importantly, surgeon's cooperation is essential for anesthesiologists to execute these maneuvers.

[TDM (therapeutic drug monitoring) for dosing theophylline].

In order to maximize the effectiveness and safety of drug therapy, it is important to individualize the dosage of potent drugs. Some drugs can not be titrated against the intensity of the therapeutic or toxic actions. Determination of the blood concentration of such drugs can be a helpful guide in adjusting the dosage during their therapeutic use. The drug dosing guided by pharmacokinetics is called TDM or therapeutic drug monitoring. In conventional pharmacokinetics, a large number of blood samples are collected from one patient to determine the individual pharmacokinetic parameters. In TDM, the pharmacokinetic parameters obtained from a group of patients who belong to a certain category are used to guide estimation of the individual pharmacokinetic parameters and only a few blood samples from one patient are sufficient to determine the individual parameters. The blood concentration of a drug and the intensity of its pharmacodynamic action, however, is not necessarily correlated. Therapeutic decisions should never be based solely on the blood concentration of a drug.

[Let's study exponential function related to anesthesiology by using computer graphics--Part II: Wash-in exponential function].

The author first explained the wash-in exponential function. Then mathematically simulated changes in the concentration of inhalation anesthetic inside a breathing circle during induction of anesthesia were shown as a physical model related to anesthesiology to explain the idea of wash-in exponential function. Effect of the flow rate and concentration of anesthetic delivered to a breathing circle on the changes in the anesthetic concentration inhaled by patients was calculated and graphed by using a computer program developed for science education. The author also stressed the importance of graphic expression in understanding various physical or biophysical phenomena related to anesthesiology.

[Let's study exponential function related to anesthesiology by using computer graphics--Part I: Wash-out exponential function].

A computer simulation is used to analyze physical or biophysical changes related to anesthesiology mostly by computer oriented experts. Recent development in a personal computer and its program, however, has made it possible for more anesthesiologists to have an experience of computer analysis. For example, graphic expression of exponential functions can easily be obtained by using a computer program, such as "Graphnote" by Fukutake Pub. Co. In this literature, the author first explained the wash-out exponential function. Then estimation of changes in the hematocrit and serum protein concentration associated with blood loss during surgery was given as an example of biophysical phenomena related to anesthesiology, to which the wash-out exponential function is applicable for mathematical simulation. Besides, the author demonstrated the way to draw exponential function curves by using "Graphnote", so that the readers can express the curves by themselves.

[Effect of nitroglycerin and nicardipine on ICG excretion during halothane anesthesia].

We evaluated the effect of nitroglycerin and nicardipine on ICG excretion during halothane anesthesia in man. Induced hypotension with nitroglycerin during halothane anesthesia produced a significant prolongation in ICG excretion. No such significant prolongation occurred in the patients who received nicardipine. The results suggest that a reduction in hepatic blood flow during anesthesia may be much less in patients who receive halothane with nicardipine than in those who receive halothane with nitroglycerin.

[Effect of isoflurane and enflurane on ICG-clearance].

We performed ICG-test (indo-cyanine green test) during surgery to study the effect of isoflurane and enflurane on ICG clearance in human. When the systolic arterial pressure (SAP) was maintained at 70% of the preoperative base line value, a significant decrease in ICG clearance occurred in the patients who received enflurane. Isoflurane, on the contrary, did not cause such a decrease in the ICG clearance. We conclude that isoflurane may restore either the blood flow to the liver or the liver function and the liver may remove ICG from the blood much better under isoflurane than under enflurane.

[Perioperative blood glucose levels in children].

The perioperative blood glucose (BG) level may represent autonomic responses to various stresses by anesthesia and surgery. We studied the effects of regional blocks combined with general anesthesia on the BG response in pediatric patients. We could not find any significant differences in BG levels between blocked and non-blocked patients. However, BG levels of the children who had been hysterical or crying during the induction of anesthesia were significantly higher than those of the children who had been calm or sleeping. Forty healthy children, aged 1-3 yrs who were scheduled for elective urological surgery were studied. Anesthesia was induced with halothane in oxygen. The anesthesiologist recorded the children's attitude before and during the induction of anesthesia, and described as "calm or asleep (Calm-group), and hysterical or crying (Crying-group)". Patients were assigned randomly to two groups as follow; Group A (n = 20): receiving nerve blocks, Group B (n = 20): without the blocks. The anesthesia was maintained with 1-2.5% halothane in oxygen required to maintain the hemodynamic parameters within 10% of baseline value before surgery. Both groups received lactated-Ringer's solution during the study period. The venous BG levels were determined 5 times, i.e. immediately after asleep, 5, 15, 30 minutes after skin incision and at the conclusion of surgery. BG levels were compared between groups using Mann-Whitney Test. There was no significant difference in BG levels between Group A and B throughout the study period. But BG values of Crying-group (n = 9) were significantly higher than those of Calm-group (n = 31) during perioperative period.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of the prone position on ICG excretion during normotensive or hypotensive isoflurane anesthesia].

We evaluated the effect of prone position on ICG excretion during normotensive and hypotensive isoflurane anesthesia. In supine position, either normotensive or hypotensive anesthesia produced no significant prolongation in ICG excretion. In prone position, however, both normotensive and hypotensive anesthesia caused a significant prolongation in the excretion. The results suggest that prone position decreases the hepatic blood flow or hepatic function during isoflurane anesthesia.

[Convenient and useful computer software for the anesthesiologist].

Convenient and useful computer software for the anesthesiologist to draw figures for presentation, or to perform statistical analysis were presented. Each software is selected in the condition that it does not need special optional hardware, and processes the data quickly even with an old type computer, and also that even a computer beginner can easily operate it. The presented software are as follows: 1) Silhouette (drawing figures), 2) NEO (drawing figures), 3) Graph note (drawing figures), 4) Chart up science (drawing figures), 5) Z's word JG (making slide manuscripts) and 6) Biostat (doing statistical analysis).

[Determination of fentanyl concentrations in the blood with the application of high performance liquid chromatography].

We developed a method to determine the blood concentration of fentanyl by using reverse phase partition liquid chromatography. The extract rate of fentanyl from blood 10 ml was 79 +/- 2%, and the minimum detective concentration of fentanyl was 158 pg.ml-1. These performances are sufficient to determine the blood concentration of fentanyl in clinical anesthesia.

[Effect of dopamine administration on ICG-disappearance rate during prone position anesthesia].

We evaluated the effect of dopamine administration (3 micrograms.kg-1.min-1) on ICG-disappearance rate during prone position in 10 patients undergoing elective spinal cord surgery. Anesthesia was maintained with isoflurane and 50% nitrous oxide in oxygen. ICG-disappearance rate was determined at 3 points, i.e., the day before surgery, during prone position and during the administration of dopamine. Systolic arterial pressure showed no significant difference before and during dopamine administration. ICG-disappearance rate during prone position was significantly lower than the preoperative value. However, ICG-disappearance rate showed no significant difference during dopamine administration and preoperative period. We conclude that dopamine administration may attenuate the depressant effect of the prone position on the hepatic blood flow.

[ICG-disappearance rate during sevoflurane- or neurolept anesthesia].

We evaluated the effect of sevoflurane or neuroleptanesthesia on ICG-disappearance rate in 22 patients undergoing elective extra-abdominal surgery. We divided the patients into three groups, i.e., SN-group (n = 8), SH-group (n = 8) and NLA-group (n = 6). Systolic arterial pressure (SAP) in the patients of SN-group or SH-group was maintained with sevoflurane at about 100% or 70% of the preoperative value respectively. There was no significant difference in SAP between SN-group and NLA-group. In SN-group and NLA-group, there was no significant difference in the ICG-disappearance rate between the values during anesthesia and those during preoperative period. In SH-group, however, it was significantly lower than the preoperative value. We conclude that, when normal systolic arterial pressure can be maintained, sevoflurane or neuroleptanesthesia has little effect on the liver function and hepatic blood flow. Sevoflurane anesthesia with 70% of preoperative SAP, however, may depress the liver function and hepatic blood flow.