Malignant hyperthermia triggered by isoflurane and suxamethonium in a patient who underwent apparently uneventful halothane anesthesia previously: a case report.
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Journal Article↗
Biomedical subjects
A Matsuki
Publications and source records attributed to A Matsuki.
Renin-aldosterone system and atrial natriuretic peptide during anesthesia in orthopedic patients over 80 years of age.
STUDY OBJECTIVES: To investigate the changes in plasma atrial natriuretic peptide, renin activity, and aldosterone during isoflurane anesthesia in patients over 80 years. DESIGN: Prospective, randomized, controlled study. SETTING: Operating rooms and postanesthesia recovery room of Hirosaki University Hospital and Hakodate Watanabe Hospital. PATIENTS: 36 patients undergoing reduction of femur neck fracture (18 patients ranging in age from 80 to 99 years and 18 patients ranging in age from 40 to 59 years as control). INTERVENTION: In all patients, anesthesia was induced with intravenous (i.v.) thiopental sodium 3 to 5 mg/kg succinylcholine 0.5 to 1.0 mg/kg for facilitating tracheal intubation and was maintained with 1.2% to 2.0% isoflurane in 50% oxygen. MEASUREMENTS AND MAIN RESULTS: Plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA), and plasma aldosterone (PA) levels were assayed. Blood samples were obtained on the following occasions: before the induction of anesthesia, 15 minutes after skin incision, 90 minutes after anesthesia induction, and the 60 minutes after the end of surgery. Plasma renin activity and PA levels in patients from 40 to 59 years increased significantly 90 minutes after induction, whereas PRA and PA levels in patients over 80 years were unchanged. There were significant differences in PRA and PA levels between both groups at any time of measurements. Plasma ANP levels of patients over 80 years were significantly elevated at 90 minutes induction. Plasma ANP levels in patients over 80 years at 90 minutes after the induction and 60 minutes after the end of surgery were significantly higher than those of patients from 40 to 59 years. Plasma renin activity in hypertensive patients over 80 years at 90 minutes after the induction was significantly lower than that observed in normotensive patients. The renal loss of sodium was increased in the hypertensive patients. CONCLUSIONS: Orthopedic patients over 80 years of age have decreased PRA and PA, increased ANP, and renal loss of sodium as compared with patients 40 to 59 years, during isoflurane anesthesia. Plasma renin activity at 90 minutes after induction was decreased in hypertensive patients over 80 years, but PA and ANP were not affected by hypertension during anesthesia.
Adult↗
The effect of ketamine on clinical endpoints of hypnosis and EEG variables during propofol infusion.
BACKGROUND: We studied the effect of variable doses of ketamine on the endpoints of hypnosis, e.g., unresponsiveness to verbal commands (UVC), loss of eyelash reflex (LER), and inhibition of body movement response with or without sneezing to nasal membrane stimulation (INBMR), and processed EEG variables, e.g., bispectral index (BIS), 95% spectral edge frequency (SEF) and median frequency (MF) during propofol infusion. METHODS: Forty-eight patients received either propofol infusion, 30 mg.kg-1.h-1 (Group P; n = 12) or ketamine bolus, 0.25, 0.5 or 0.75 mg i.v., followed by propofol infusion, 30 mg.kg-1.h-1 + variable dose ketamine infusion, 0.25, 0.5 or 0.75 mg.kg-1.h-1 (Groups PK0.25, PK0.5 and PK0.75; n = 12 each) until UVC, LER and INBMR. BIS, 95% SEF and MF values were monitored and recorded at the endpoints of hypnosis. Propofol and ketamine concentrations were measured at INBMR. RESULTS: Propofol infusion, 30 mg.kg-1.h-1, induced UVC, LER and INBMR at BIS: 65 +/- 2, 63 +/- 9 and 33 +/- 7; 95% SEF: 17 +/- 3, 17 +/- 4 and 14 +/- 3; and MF values of 5 +/- 2, 5 +/- 3 and 3 +/- 2, respectively. With adjunctive ketamine (Groups PK0.5 and PK0.75), the hypnotic endpoints were achieved at higher BIS and 95% SEF values and lower propofol doses and concentrations as compared to Groups P and PK0.25 (9.9 +/- 5.8 and 9.4 +/- 3.4 vs. 13.4 +/- 4.5 and 14 +/- 5.8 micrograms.ml-1). CONCLUSIONS: Our results suggest additive interaction between propofol and ketamine (Groups PK0.5 and PK0.75) for achieving the hypnotic endpoints; however, ketamine did not depress the EEG variables in proportion to its hypnotic effect. The paradoxically higher BIS and 95% SEF values at the hypnotic endpoints may be due to lower propofol concentrations and/or no effect of ketamine on the EEG variables.
Adult↗
Is total body weight an appropriate predictor for propofol maintenance dose?
BACKGROUND: Infusion rate of propofol during anaesthesia is usually based on total body weight. In this study, we have determined the relationship between total body weight and plasma propofol levels when the infusion rate was based on total body weight. METHODS: Sixty patients undergoing elective surgery were studied. Anaesthesia was induced with propofol 1 mg x kg(-1), ketamine 1 mg x kg(-1) and fentanyl 2 microg x kg(-1), and maintained with propofol 5 mg x kg(-1) x h(-1), ketamine 0.5-1 mg x kg(1) x h(-1) and fentanyl 5-15 microg x kg(-1). Propofol infusion rate did not change during anaesthesia, and infusion was terminated at the end of surgery. Immediately prior to termination of the propofol infusion, arterial blood (5 ml) was collected to measure plasma level of propofol by a high-performance liquid chromatography equipped with electrochemical detection. RESULTS: There was a significant correlation between plasma propofol and total body weight (r=0.646, P<0.001). Plasma propofol concentration also correlated with infusion rate, corrected to lean body mass (r=0.527, P<0.001). CONCLUSION: During a fixed infusion rate, plasma propofol concentration may be dependent on total body weight.
Anesthetics, Dissociative↗
Estimation of the initial distribution volume of glucose by an incremental plasma glucose level at 3 min after i.v. glucose in humans.
AIMS: The initial distribution volume of glucose (IDVG) could be a clinically useful indicator of the central extracellular fluid (ECF) space volume, namely the interstitial fluid volume status of highly perfused organs. In this study, we determined the formula of IDVG using incremental plasma glucose levels after i.v. glucose. METHODS: One hundred and fifty patients admitted to the general intensive care unit of the University of Hirosaki hospital were entered into this prospective study which was conducted in two stages. In the first stage 300 data points from 100 patients were used to measure the IDVG (3 determinations for each patients). This utilized a one compartment model to describe the incremental plasma glucose decay curve following an intravenous bolus injection of glucose which, in turn, was used to derive the parameters of an equation for IDVG prediction following a single plasma sample. The second stage was a validation of the equation using a separate data set (150 points) from a further 50 patients. RESULTS: A one phase exponential decay model was well-fitted for the IDVG-postadministration glucose level curve, and indicated that the incremental glucose level at 3 min after i.v. glucose was best-correlated to the IDVG compared with those at 1, 2, 4, 5 and 7 min postadministration. The formula of the IDVG was obtained from the curve: IDVG=24.44xe-0.0298xDeltaGL+2.70, where DeltaGL=incremental glucose level at 3 min after i.v. glucose. Another 150 samples showed that the measured-IDVG from a one compartment model and predicted-IDVG from the formula were 7.24+/-1. 63 and 7.27+/-1.52 l, respectively, and that there was a significant correlation between the two IDVGs (r=0.966, P<0.0001). CONCLUSIONS: Using an incremental glucose level at 3 min after i.v. glucose, we have established the reliable formula for determination of the IDVG which could be a clinically useful indicator of the central ECF volume.
Blood Glucose↗
Hypnotic endpoints vs. the bispectral index, 95% spectral edge frequency and median frequency during propofol infusion with or without fentanyl.
Hypnotic endpoints and/or EEG variables, e.g. bispectral index, 95% spectral edge frequency and median frequency, have been studied to monitor anaesthetic (hypnotic) depth during total intravenous anaesthesia. In this study, the relation between the hypnotic endpoints of unresponsiveness to verbal commands, loss of eyelash reflex and body movement response to mechanical nasal membrane stimulation vs. bispectral index, 95% spectral edge frequency and median frequency during propofol anaesthesia with or without fentanyl is presented. Forty-two patients were randomly assigned to receive either propofol infusion, 30 mg kg-1 h-1 (n = 22), or propofol infusion, 30 mg kg-1 h-1 + fentanyl bolus, 2 micrograms kg-1 i.v. (n = 20). Bispectral index, 95% spectral edge frequency and median frequency and propofol doses were monitored and recorded at unresponsiveness to verbal commands, loss of eyelash reflex and inhibition of nasal body movement response. The bispectral index values were significantly higher in the propofol + fentanyl compared with the propofol group, i.e. 74.7 +/- 10.9, 73.1 +/- 10.5 and 47.1 +/- 9.2 vs. 65.8 +/- 9.8, 59.6 +/- 10 and 33.8 +/- 5.7 at unresponsiveness to verbal commands, loss of eyelash reflex and inhibition of nasal body movement response respectively. Doses of propofol for achieving the hypnotic endpoints were significantly lower in the propofol + fentanyl compared with the propofol group. Plasma propofol concentrations at inhibition of nasal body movement response were lower in the propofol + fentanyl compared with the propofol group (9.2 +/- 2.0 micrograms mL-1 vs. 14.1 +/- 4.2 micrograms mL-1). Our results suggest that fentanyl pretreatment potentiates the effects of propofol and achieves the hypnotic endpoints at higher bispectral index values and lower propofol doses and concentrations (measured at inhibition of nasal body movement response).
Adjuvants, Anesthesia↗
Renin-aldosterone in elderly patients with hyperkalaemia under anaesthesia.
Elderly patients with hyperkalaemia often have low concentrations of plasma renin and aldosterone, perhaps secondary to reduced glomerular filtration and sympathetic insufficiency. The endocrine response to surgical stress and volume expansion during anaesthesia was studied in seven elderly patients with hyperkalaemia (mean age 87.7 +/- SD 5.3 years), 18 elderly patients without hyperkalaemia (86.5 +/- 5.5 years), and 18 younger patients (52.6 +/- 7.2 years) as controls. Base-line values, in hyperkalaemic elderly patients, for plasma renin activity and plasma aldosterone concentration were 0.8 +/- 0.3 ng mL-1 h-1 and 2.8 +/- 0.8 pg mL-1 respectively (significantly lower than in the younger patients), and 287 +/- 42 pg mL-1 for plasma atrial natriuretic peptide levels, which were significantly higher. The plasma renin activity and aldosterone concentrations in elderly patients with hyperkalaemia were at all times lower, but not significantly, than those of the elderly patients without hyperkalaemia. The atrial natriuretic peptide concentrations (351 +/- 48 pg mL-1) in the hyperkalaemic elderly were significantly higher 90 min after induction of anaesthesia than in the normokalaemic elderly (108 +/- 38 pg mL-1). Hormone concentrations in the hyperkalaemic patients did not change during anaesthesia, but plasma atrial natriuretic peptide concentrations increased significantly in the normokalaemic elderly, and plasma renin activity and aldosterone of the younger patients increased significantly during anaesthesia. These results indicate that plasma renin activity, and the concentrations of aldosterone and of atrial natriuretic peptide in elderly patients with hyperkalaemia are unresponsive to surgical stress and volume expansion.
Adult↗
Relation between bispectral index and plasma catecholamines after oral diazepam premedication.
The efficacy of anaesthetic premedication has been assessed using sedative scores or a visual analogue scale. However, in both it may be difficult to exclude evaluators' subjectivity or a placebo effect. Plasma concentration of catecholamines may also be useful for the assessment of patient anxiety. Recently bispectral electro-encephalographic analysis has been developed, and the bispectral index monitor has been reported to give measurements which correlate well with the depth of sedation. In the present study, we have examined the relation between bispectral index values and plasma catecholamine concentrations after oral diazepam premedication. Twenty-eight patients scheduled for elective surgery were randomly assigned to one of two groups: diazepam premedication group (group D(+), n = 14) and no premedication group (group D(-), n = 14). The patients were premedicated orally with diazepam 10 mg and roxatidine 75 mg in group D(+), and with roxatidine 75 mg only in group D(-) 90 min before arrival in the operating theatre. After patients arrived in the operating theatre, the bispectral index monitor was applied. Venous blood samples (6 mL) were collected in the case of patients in group D(+) for the measurement of plasma catecholamines levels using high-performance liquid chromatography. The bispectral index level (mean +/- SD) in group D(+): 93.5 +/- 773.5 was significantly lower than that in group D(-): 96.1 +/- 1.8 (P < 0.05). There was a significant correlation between bispectral index and plasma norepinephrine levels (r = 0.567, P < 0.05). The present study suggests that the bispectral index monitor may detect the effect of oral diazepam premedication.
Administration, Oral↗
Movement response to skin incision: analgesia vs. bispectral index and 95% spectral edge frequency.
We studied the movement response to skin incision in 68 adult (males/females) ASA I-II patients receiving propofol +/- fentanyl intravenous anaesthesia using the bispectral index and 95% spectral edge frequency monitoring with an A-1050 EEG monitor. Following Ethics Committee approval, patients were randomly assigned to one of the following four treatments: Group P (n = 17): propofol infusion, 1 mg kg-1 min-1 intravenous for 2 min, followed by propofol infusion, 200 micrograms kg-1 min-1, until skin incision; Group PF1 (n = 17): fentanyl bolus, 1 microgram kg-1 intravenous + propofol infusion as in Group P; Group PF2 (n = 17): fentanyl bolus, 2 micrograms kg-1 intravenous + propofol infusion as in Group P; and Group PF3 (n = 17): fentanyl bolus, 3 micrograms kg-1 intravenous + propofol infusion as in Group P. The bispectral index and 95% spectral edge frequency were monitored continuously and recorded prior to induction of anaesthesia (base-line) and at skin incision. Twelve, 10, 4 and 4 patients responded to skin incision in Groups P, PF1, PF2 and PF3, respectively (P and PF1 vs. PF2 or PF3; P = 0.0001, and 0.006). The bispectral index and 95% spectral edge frequency were significantly lower at skin incision compared with the base-line values in all the four treatment groups. However, only bispectral index values were significantly lower in the nonmovement as compared with the movement (M) category (32.6 +/- 8.9 vs. 37.4 +/- 10.3; P = 0.04). Though deeper levels of hypnosis to lower bispectral index and 95% spectral edge frequency values may be effective in preventing the movement response to skin incision, provision of adequate analgesia rather than lower bispectral index and 95% spectral edge frequency (clinical maintenance) values may be more reliable for preventing the response to skin incision as bispectral index and 95% spectral edge frequency measure the hypnotic component of the anaesthetic effect. Lower bispectral index values may be more discriminatory as compared with 95% spectral edge frequency values for preventing the movement response to skin-incision.
Adolescent↗
The effects of nitrous oxide and ketamine on the bispectral index and 95% spectral edge frequency during propofol-fentanyl anaesthesia.
In this study, we have sought to establish whether N2O and ketamine alter the bispectral index during propofol-fentanyl anaesthesia. Fourteen surgical patients were randomly assigned to one of two groups: the N2O group (n = 7) and the ketamine group (n = 7). In both groups, anaesthesia was induced with propofol 1.5-2 mg kg-1 and fentanyl 2 micrograms kg-1 and maintained with propofol 5-7 mg kg-1 hr-1 to target the bispectral index between 40 and 50. After the bispectral index value had stabilized the propofol infusion rate was fixed. In the N2O group, the following concentrations of N2O were subsequently inhaled at 20-min intervals; 20, 40, 60 and 70%, and then N2O was terminated. In the ketamine group, ketamine (0.4 mg kg-1 + 1.0 mg kg-1h-1) was given. The bispectral index and 95% spectral edge frequency were recorded 20 min after each change in concentration of N2O or ketamine infusion. The bispectral index and 95% spectral edge frequency did not change significantly in the N2O group, but increased significantly from 44.1 +/- 0.7 and 16.0 +/- 0.5 to 58.6 +/- 1.4 and 19.5 +/- 0.3 (P < 0.01), respectively, in the ketamine group. Additional N2O or ketamine did not decrease the bispectral index and 95% spectral edge frequency values. The depth of sedation should be assessed carefully using a bispectral index monitor when these anaesthetic agents are used together.
Adult↗
I.v. lidocaine worsens histamine-induced bronchoconstriction in dogs.
We have assessed the effect of lidocaine (lignocaine) on histamine-induced bronchoconstriction by direct visualization with a superfine fibreoptic bronchoscope. Seven mongrel dogs were anaesthetized with pentobarbital (pentobarbitone) 30 mg kg-1 followed by 2 mg kg-1 h-1 and pancuronium 200 micrograms kg-1 h-1. The trachea was intubated with a tracheal tube containing a second lumen for insertion of a 2.2-mm fibreoptic bronchoscope. This allowed estimation of the bronchial cross-sectional area (BCA) of the third bronchial bifurcation of the right lung. We used NIH image, a public domain image processing and analysis program. Bronchoconstriction was produced with a bolus dose of histamine 10 micrograms kg-1 i.v. followed by continuous infusion of 500 micrograms kg-1 h-1. After 30 min the following i.v. doses of lidocaine were given: lidocaine 0 (saline), 0.01, 0.1, 1.0 and 10 mg kg-1 at 10-min intervals. BCA was assessed 90 s after each dose. Arterial blood sampling was performed for measurement of plasma catecholamines. Lidocaine 1.0 and 10 mg kg-1 significantly reduced histamine-decreased BCA from 69.7 (SEM 4.1)% to 59.8 (7.3)% and 34.3 (6.8)%, respectively. Plasma concentrations of catecholamines decreased significantly after lidocaine 10 mg kg-1 i.v. In addition, there was a significant correlation between percentage decreases in plasma concentrations of epinephrine (adrenaline) and norepinephrine (noradrenaline) and reduction in %BCA (epinephrine-BCA, P < 0.01, r = 0.674; norepinephrine-BCA, P < 0.01, r = 0.510). This study suggests that i.v. lidocaine may exacerbate histamine-induced bronchoconstriction by a sympatholytic effect. This may have therapeutic implications for patients with acute asthma or anaphylactic shock who may become dependent on circulating catecholamines.
Anesthetics, Intravenous↗
Relaxant effect of propofol on the airway in dogs.
Propofol has been suggested to produce airway relaxant effects in vivo, although the mechanism is unclear. We have evaluated the bronchodilating effect of propofol using a direct visualization method with a superfine fibreoptic bronchoscope. We studied 21 mongrel dogs anaesthetized with pentobarbital 30 mg kg-1 i.v. and pancuronium 0.2 mg kg-1 h-1. The animals were allocated randomly to one of three groups (n = 7 in each): propofol group, atropine-propofol group and histamine-propofol group. The trachea was intubated using a tracheal tube that had a second lumen for insertion of the bronchoscope to monitor continuously bronchial cross-sectional area (BCA). BCA was measured using the NIH Image program. In the propofol group, dogs were given the following doses of propofol at 10-min intervals: 0 (saline), 0.2, 2.0 and 20 mg kg-1 i.v. In the atropine-propofol group, saline, atropine 0.2 mg kg-1 and propofol 20 mg kg-1 were given at 10-min intervals. In the histamine-propofol group, bronchoconstriction was elicited with histamine 10 micrograms kg-1 and 500 micrograms kg-1 h-1 until the end of the experiment. Thirty minutes after the start of infusion of histamine, propofol (0, 0.2, 2.0 and 20 mg kg-1) was administered. Changes in BCA were expressed as percentage of basal area. Histamine decreased BCA by 39.2 (SEM 5.4%). Propofol increased significantly basal and histamine-decreased BCA in a dose-dependent manner by 18.4 (4.5%) and 15.8 (4.9%), respectively after 20 mg kg-1 i.v. However, propofol following atropine i.v. did not increase BCA (129.9 (8.2)% after atropine vs 125.7 (8.9)% after propofol). Therefore, the relaxant effect of propofol may be a result of reduction in vagal tone.
Anesthetics, Intravenous↗
Inhibitory effect of clonidine on ketamine-induced norepinephrine release from the medial prefrontal cortex in rats.
We have investigated the effect of clonidine on ketamine-induced norepinephrine release from the medial prefrontal cortex in rats using microdialysis. Twenty-one male Wistar rats weighing 200-300 g were allocated randomly to one of four groups: i.p. injection of ketamine 100 mg kg-1 with clonidine 0 (saline: group C0, n = 6), 3 (group C3, n = 5), 30 (group C30, n = 5) and 300 micrograms kg-1 (group C300, n = 5). As reported previously, ketamine increases norepinephrine release. In groups C0 and C3, marked increases in norepinephrine release were observed with maximum values of mean 483 (SEM 55)% and 412 (53)% compared with basal values, respectively. Although significant increases in norepinephrine release were also observed (276 (43)%) in group C30, they were significantly lower than those in groups C0 and C3 (P < 0.01 and P < 0.05, respectively). In group C300, there was a significant reduction in norepinephrine release (62 (13)%) compared with basal and the three other groups (P < 0.01). This inhibitory effect of clonidine on norepinephrine may be related to reduction in undesirable emergence reactions after ketamine anaesthesia.
Adrenergic alpha-Agonists↗
The relaxant effect of propofol on guinea pig tracheal muscle is independent of airway epithelial function and beta-adrenoceptor activity.
UNLABELLED: Airway epithelium and vascular endothelium modulate the tension of the underlying smooth muscle by releasing relaxing factors such as prostanoids and nitric oxide (NO). We investigated whether the relaxant effect of propofol on airway smooth muscle is dependent on airway epithelial function. Tracheal spirals of female guinea pigs were mounted in water-jacketed organ baths filled with Krebs-bicarbonate buffer aerated with 95% O2 and 5% CO2 at 37 degrees C. Changes in isometric tension of the specimens were measured with a force-displacement transducer and recorded with a polygraph. Propofol (10(-4) to 10(-3) M) inhibited carbachol (CCh)-, histamine (HA)-, or endothelin-1-induced contractions of the muscles in a dose-dependent manner. Neither mechanical removal of the epithelial layer, chemical inhibition of epithelial synthesis of prostanoids, nor NO affected the relaxant effect of propofol on CCh- or HA-induced tracheal contraction. Furthermore, the blockade of beta-adrenoceptors did not change the relaxant effect of propofol. These results indicate that the relaxant effect of propofol on the airway smooth muscle is independent of the epithelial function or beta-adrenoceptor activity. Propofol is an excellent anesthetic for patients with hyperreactive airways in which the epithelial layer is damaged. IMPLICATIONS: Airway epithelium, as well as vascular endothelium, plays an important role in modulating the baseline tone and reactivity of underlying smooth muscle. We investigated, in vitro, whether the relaxant effect of propofol on airway smooth muscle is dependent on airway epithelial function. We suggest that propofol relaxes airway smooth muscle independently of the epithelial function.
Anesthetics, Intravenous↗
Ketamine inhibits inositol 1,4,5-trisphosphate production depending on the extracellular Ca2+ concentration in neonatal rat cardiomyocytes.
UNLABELLED: We investigated the effect of ketamine on inositol 1,4,5-trisphosphate (IP3) formation in rat cardiomyocytes. After the addition of 1 micromol/L ketamine, IP3 production in the presence of 0.5, 1, 5, 10, and 30 mmol/L Ca2+ significantly decreased from 537.1+/-8.3, 590.7+/-12.9, 690.6+/-7.9, 754.8+/-12.5, and 823.7+/-15.2 pmol/mg protein to 467.0+/-8.3, 483.8+/-11.0, 512.6+/-21.3, 612.1+/-16.9, and 652.6+/-17.3 pmol/mg protein, respectively. When exposed to TMB-8 (a intracellular calcium inhibitor), IP3 production decreased significantly from 347.2+/-27.3 to 283.8+/-20.4 pmol/mg protein in the presence of 1 micromol/L ketamine, but A23187, which increases intracellular calcium, did not affect the inhibition of IP3 production by ketamine. These results demonstrate that ketamine decreases IP3 formation through inhibition of the calcium ion-sensing receptor and that IP3 formation reduced by ketamine is not affected by the alteration of intracellular calcium. IMPLICATIONS: Ketamine has a negative inotropic effect in isolated cardiomyocytes. The negative inotropic effect was associated with a decrease in inositol 1,4,5-trisphosphate production, and the inhibitory action was enhanced depending on the concentration of extracellular Ca2+.
Anesthetics, Dissociative↗
Volatile anesthetics augment expression of proinflammatory cytokines in rat alveolar macrophages during mechanical ventilation.
BACKGROUND: Previous studies indicate that anesthesia and surgery induce an inflammatory reaction in alveolar macro phages. However,they filed to independently evaluate the relative contributions of factors including mechanical ventilation, general anesthesia, and surgical stress. Therefore, the authors tested the hypothesis that inflammatory reactions at the cellular level in alveolar macrophages are induced within 2 h of inhalation of volatile anesthetics under mechanical ventilation. METHODS: After administration of pentobarbital, rats were allocated to the nonventilated control or spontaneous or mechanical ventilation (n = 15/group) for 2 h at a fraction of inspired oxygen (FI(O2)) of 0.21. In a separate series of experiments, rats were mechanically ventilated without volatile anesthesia, or during exposure to halothane, enflurane, isoflurane, or sevoflurane (n = 15/group). Pulmonary lavage was performed, and RNA was extracted from harvested cells. The mRNA for the proinflammatory cytokines interleukin (IL)-1alpha, IL-1beta, IL-6, macrophage inflammatory protein-2 (MIP-2), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) were measured by semiquantitative reverse transcription-polymerase chain reaction using beta-actin as an internal standard. Pulmonary lavage concentrations of these cytokines were measured by enzyme-linked immunoassay. RESULTS: The lavage cell count and cytology were similar in each series of the experiment. Gene expression of MIP-2 and TNF-alpha was greater during mechanical than spontaneous ventilation and nonventilation control However, the concentrations of cytokines except MIP-2 and TNF-alpha were less than detection levels. During exposure to volatile anesthetics, gene expression for IL-1beta, MIP-2, IFN-gamma, and TNF-alpha all increased significantly compared with mechanical ventilation alone. Significant increases in lavage concentrations of MIP-2 and TNF-alpha were also observed. CONCLUSIONS: Gene expression of proinflammatory cytokines increase after inhalation of volatile anesthetics under mechanical ventilation. These data indicate that inhalation of volatile anesthetics under mechanical ventilation induces an inflammatory response at the transcriptional level within 2 h.
Anesthetics, Inhalation↗
Exposure to cigarette smoke impairs alveolar macrophage functions during halothane and isoflurane anesthesia in rats.
BACKGROUND: Smoking alters numerous alveolar macrophage functions and is an important risk factor for postoperative pulmonary complications. The authors therefore tested the hypothesis that smoke exposure impairs antimicrobial and proinflammatory responses in alveolar macrophages during halothane and isoflurane anesthesia with mechanical ventilation. METHODS: Thirty control rats and 30 rats exposed to cigarette smoke were mechanically ventilated with 1.5 minimum alveolar concentration halothane and isoflurane. Ten smoke-exposed and control animals were assigned to one of three different anesthetic durations (0, 2, and 6 h). The fraction of aggregated cells and cell distribution were determined. Opsonized and unopsonized phagocytosis was measured. Microbicidal activity was determined as the ability to kill Listeria monocytogenes. The expression of interleukin (IL)-1alpha, IL-1beta, IL-6, macrophage inflammatory protein-2, interferon-gamma, and tumor necrosis factor-alpha was measured by semiquantitative reverse-transcription polymerase chain reaction. Pulmonary lavage concentrations of these cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: During both halothane and isoflurane anesthesia, the fraction of aggregated macrophages increased, whereas unopsonized and opsonized phagocytosis and microbicidal activity decreased significantly over time in both groups. Responses observed in smoke-exposed rats were almost twice as great as those observed in the control rats. Gene expression and production of all proinflammatory cytokines except IL-6 increased 2-20-fold during anesthesia. The increases in IL-1beta, interferon-gamma, and tumor necrosis factor-alpha in the control rats were 1.5-8 times greater than those in the smoke-exposed rats. CONCLUSION: Antimicrobial and proinflammatory responses of alveolar macrophages during anesthesia were markedly suppressed by smoke exposure. Our data suggest that smoke exposure reduces the efficacy of immune defenses during anesthesia.
Anesthesia, Inhalation↗
Relaxant effect of magnesium and zinc on histamine-induced bronchoconstriction in dogs.
OBJECTIVE: Magnesium sulfate (MgSO4) has been reported to produce bronchodilation in asthmatic patients. In vitro studies have suggested that divalent cations inhibit L-type voltage-sensitive calcium ion (Ca2+) channels in cardiac and smooth muscles. In this study, we evaluated the in vitro and in vivo effects of magnesium ion (Mg2+) and zinc ion (Zn2+) on the airway contracted by histamine. SETTING: A university research laboratory. SUBJECTS IN VITRO: Tracheal smooth muscle from guinea pigs. IN VIVO: Mongrel dogs. MEASUREMENTS AND MAIN RESULTS IN VITRO STUDY: The tension of isolated guinea pig tracheal strips was measured isometrically with a force displacement transducer. The specimen was contracted with histamine (10 microM). Then, MgSO4 (n = 6), zinc sulfate (ZnSO4, n = 6), or sodium sulfate (Na2SO4, n = 6) was cumulatively added to the organ bath. IN VIVO STUDY: The bronchial cross-sectional area of mongrel dogs was measured by a direct visualization method demonstrated previously. The dogs were randomly assigned to three groups: group Mg (n = 7), group Zn (n = 7), and group Na (n = 7). Bronchoconstriction was elicited with histamine (10 microg/kg plus 500 microg/kg/hr iv). Thirty minutes after the start of histamine infusion, 0 (saline), 1, 10, and 100 micromol/kg ZnSO4 or 1, 10, 100, and 1000 micromol/kg MgSO4 or Na2SO4 were administered intravenously in group Zn, Mg, or Na, respectively. The bronchial cross-sectional area was assessed before (basal) and 30 mins after the start of histamine infusion and 5 mins after each dose of ZnSO4, MgSO4, or Na2SO4. Arterial blood was also obtained to measure plasma levels of epinephrine and norepinephrine by gas chromatography-mass spectrometry. All data are expressed as mean +/- SEM. The doses of the divalent cations that reversed histamine-induced contraction by 50% were calculated by GraphPad Prism. MgSO4 and ZnSO4 (9.38+/-0.28 and 1.84+/-0.30 mM, respectively) relaxed histamine-contracted tracheal strip in a concentration-dependent manner, whereas Na2SO4 did not. Similarly, the in vivo study showed that MgSO4 and ZnSO4 dose-dependently reversed histamine-induced bronchoconstriction (potency, ZnSO4 > MgSO4), whereas Na2SO4 did not. In groups Mg and Zn, the plasma catecholamine levels also dose-dependently increased except when 1000 micromol/kg MgSO4 was administered. CONCLUSION: Because the divalent cations tested produced a spasmolytic effect on the contracted airway, infusion of divalent cations might be effective against asthmatic attack. However, high concentrations of these cations produce significant toxicity, so dosage will be an important concern in development of these agents.
Animals↗