Hemodynamic stability during induction of anesthesia and tracheal intubation with propofol plus fentanyl, ketamine, and fentanyl-ketamine

Purpose. This study was conducted to investigate hemodynamic and cardiac stability during anesthesia induction and intubation, using propofol plus fentanyl, propofol plus ketamine, and propofol plus fentanyl and ketamine. Methods. Forty-five adult patients were randomly allocated to one of three groups according to the agents used for induction: propofol (2 mg/kg) plus fentanyl (3 μg/kg) (PF), propofol (2 mg/kg) plus ketamine (0.1 mg/kg) (PK), and propofol (2 mg/kg) plus fentanyl (3 μg/kg) plus ketamine (0.1 mg/kg) (PFK). Hemodynamic responses were assessed by measuring changes in blood pressure (BP), heart rate (HR), and cardiac output (CO; using dye dilution combined with pulse dye densitometry [PDD]). Results. BP and HR changes during the induction of anesthesia tended to be greater in the PK group than in the PF and PFK groups. After the injection of propofol, the cardiac index (CI) fell significantly below baseline values in the PF and PFK groups, but remained unchanged in the PK group. After tracheal intubation, BP and HR increased significantly only in the PF and PK groups, and reached a level significantly above baseline values only in the PK group. The CO responses to tracheal intubation were: PK group > PF group > PFK group. Conclusion. A combination of propofol plus fentanyl plus ketamine would provide greater reduction of fluctuations in hemodynamic variables associated with induction of anesthesia and tracheal intubation than combinations of propofol plus fentanyl or propofol plus ketamine. Received: January 22, 2001 / Accepted: June 19, 2001     

Slow EEG-power spectra correlate with haemodynamic changes during laryngoscopy and intubation following induction with fentanyl or sufentanil.

We studied nociception-associated arousal following laryngoscopy and intubation in patients scheduled for elective open heart surgery, using EEG power spectra and hemodynamics. Either fentanyl (7 micrograms/kg; n = 30) or sufentanil (1 microgram/kg; n = 30) were given in a randomized fashion to induce anesthesia in heavily premedicated patients, followed by pancuronium bromide (100 micrograms/kg). EEG-power spectra (delta, theta, alpha, beta) as well as mean arterial blood pressure (MAP) and heart rate (HF) were measured at the following end-points: before the induction of anesthesia (control), 1 and 10 minutes after laryngoscopy and intubation (L & I). Linear regression analysis was computed to determine which of the EEG power spectra was most sensitive to detect insufficient blockade of nociceptive-related arousal when correlated with haemodynamics. In the fentanyl group the change in HF closely correlated with the decrease of power in the slow delta- and theta-domain (r2 = 0.98 and r2 = 0.89 respectively) of the EEG. The change in MAP also closely correlated with a decrease in the slow delta- and theta-domain (r2 = 0.97 and r2 = 0.99 respectively). There was little correlation in regard to spectral edge frequency (SEF) and HF and MAP changes (r2 = 0.36 and r2 = 0.12 respectively). In the sufentanil group the change in HF correlated closely with an increase of power in the fast alpha and a decrease in the slow theta-domain (r2 = 0.91 and r2 = 0.98 respectively) of the EEG. The changes in MAP closely correlated with an increase in the fast alpha-band a decrease in the slow theta-domain (r2 = 0.98 and r2 = 0.73 respectively). Also there was little correlation of SEF with HF and MAP changes (r2 = 0.09 and r2 = 0.02 respectively). Among the EEG-spectra, reduction of power in the slow delta- and theta-bands are the most sensitive parameters to determine insufficient antinociception of opioids commonly used for the induction in cardiac anesthesia. Increase of power in the alpha-band seems to be closely correlated with cortical reactivation and reduction of hypnosis, while a reduction of power especially in the deltabut more so in the theta-band of the EEG reflects nociception related arousal.     

Hemodynamic effects of muscle relaxant drugs during anesthetic induction in patients with mitral or aortic valvular heart disease.

The hemodynamic effects of three nondepolarizing skeletal muscle relaxant drug regimens were compared during the induction of general anesthesia in 64 patients with valvular heart disease using a double-blind protocol. Patients were first stratified according to primary valvular defect (aortic stenosis, aortic regurgitation, mitral stenosis, or mitral regurgitation). Next, patients were randomly allocated to a drug group, either group A (atracurium), group V (vecuronium), or group MP (metocurine plus pancuronium). Data were collected during three periods: awake, postanesthetic induction, and posttracheal intubation. Four cardiovascular variables were designated a priori as primary variables of interest. These were heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), and systemic vascular resistance index (SVRI). Patients with mitral stenosis showed two significant hemodynamic differences among muscle relaxant drug groups: (1) CI increased in group A but decreased in group MP between the awake and postinduction measurements (P = 0.032); and (2) SVRI decreased in group A but increased in group MP between the awake and postintubation periods (P = 0.034). In contrast, patients with aortic stenosis, aortic regurgitation, or mitral regurgitation demonstrated no statistically significant difference in cardiovascular responses among drug groups. Further analysis was performed using the following data: (1) other hemodynamic variables; (2) incidence of deviations from cardiovascular stability; and (3) the frequency of cardiovascular drug use. This examination showed no important differences among the muscle relaxant drug groups. The small but significant hemodynamic changes observed in mitral stenosis patients in drug groups A and MP were not noted with vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS)     

The haemodynamic effects of propofol in combination with ephedrine in elderly patients (ASA groups 3 and 4).

The marked vasodilator and negative inotropic effects of propofol are disadvantages in frail elderly patients. We investigated the safety and efficacy of adding different doses of ephedrine to propofol in order to obtund the hypotensive response. The haemodynamic effects of adding 15, 20 or 25 mg of ephedrine to 200 mg of propofol were compared to control in 40 ASA 3/4 patients over 60 years presenting for genito-urinary surgery. The addition of ephedrine to propofol appears to be an effective method of obtunding the hypotensive response to propofol at all doses used in this study. However, marked tachycardia associated with the use of ephedrine in combination with propofol occurred in the majority of patients, occasionally reaching high levels in individual patients. Due to the risk of this tachycardia inducing myocardial ischemia, we would not recommend the use in elderly patients of any of the ephedrine/propofol/mixtures studied.     

Cadaveric study of movement of an unstable atlanto‐axial (C1/C2) cervical segment during laryngoscopy and intubation using the Airtraq®, Macintosh and McCoy laryngoscopes

Concern that laryngoscopy and intubation might create or exacerbate a spinal cord injury has generated extensive research into cervical spinal movement during laryngoscopy. We performed a randomised trial on six cadavers, using three different laryngoscopes, before and after creating a type‐2 odontoid peg fracture. Our primary outcome measure was the change in the space available for the spinal cord at the C1/2 segment measured by cinefluoroscopy. Tracheal intubation was performed using a minimal view of the glottis, a bougie, and manual in‐line stabilisation. In a cadaveric model of type‐2 odontoid fracture, the space available for the cord was preserved in maximum flexion and extension, and changed little on laryngoscopy and intubation.     

3,3 diindolylmethane leads to apoptosis,decreases sperm quality,affects blood estradiol 17 β and testosterone,oestrogen (α and β) and androgen receptor levels in the reproductive system in male rats

3,3 Diindolylmethane (DIM) is a major digestive product of indole‐3 carbinol, obtained from Brassica family vegetables such as broccoli, cabbage and Brussels sprouts. This study aimed to investigate the effects of DIM on sperm parameters, histological structures of testicular tissues, blood testosterone (T) and estradiol 17‐β (E2) in male rats. Thirty‐eight male Sprague Dawley rats were used. Rats were divided into four groups: Group I: referred as Control group, received corn oil only; Group II: as DIM‐10, rats received 10 mg kg^?1 DIM; Group III: as DIM‐50, rats received 50 mg kg^?1 DIM; Group IV: as DIM‐100, received 100 mg kg^?1 DIM during 53 days. Spermatological parameters, malondialdehyde (MDA) levels of testes and serum T and E2 levels were assayed. Histopathological examinations of tests were done. DIM caused an increase in MDA levels. It decreased motility and live sperm rates and increased degeneration of testicular tissues. While DIM‐10 did not affect abnormal sperm rate, higher concentrations increased the abnormalities. Sperm density was higher in DIM‐10 groups when compared to both other groups. Only DIM‐50 had an anti‐androgenic effect among all groups. Only, DIM‐10 showed anti‐estrogenic activity as compared to higher DIM groups. In conclusion, DIM (i) had side effect on some sperm characteristics, (ii) increased the MDA levels and (iii) led to histological degeneration of testicular tissues and apoptosis in a dose‐dependent manner.     

Adenocarcinoma of prostate: Role of 17β-estradiol and 5α-dihydroterosterone binding proteins

Presence of a specific 17β-estradiol-binding protein in prostates of patients with adenocarcinoma without hormonal manipulation prior to surgical resection has been reported by us earlier.' The present study involves 40 patients with carcinoma of prostate analyzed during the period December, 1974, through June, 1978. Thirty-four patients had metastatic disease, 26 of these were manipulated hormonally after and 8 prior to receptor protein assay. The other 6 were in clinical Stage C and were subjected to transurethral resection alone. The study confirms our earlier report and outlines the role of 17β-estradiol (E₂) and possibly 5_α-dihydrotestosterone (DHT) receptor protein in hormonally responsive and refractory patients. Based on the preliminary findings it seems possible to classify the prostatic carcinoma similar to human mammary cancer for the purpose of selecting patients for endocrine manipulation or treatment with other available modalities.     

Simvastatin inhibits transforming growth factor‐β1‐induced expression of type I collagen,CTGF, and α‐SMA in keloid fibroblasts

Simvastatin, a 3‐hydroxy‐3‐methylglutaryl coenzyme‐A reductase inhibitor, is used to reduce cholesterol levels. Accumulating evidence has revealed the immunomodulatory and anti‐inflammatory effects of simvastatin that prevent cardiovascular diseases. In addition, the beneficial effects of statins on fibrosis of various organs have been reported. However, the functional effect of statins on dermal fibrosis of keloids has not yet been explored. The objective of this study was to determine whether simvastatin could affect dermal fibrosis associated with keloids. We examined the effect of simvastatin on transforming growth factor (TGF)‐β1‐induced production of type I collagen, connective tissue growth factor (CTGF or CCN2), and α‐smooth muscle actin (α‐SMA). Keloid fibroblasts were cultured and exposed to different concentrations of simvastatin in the presence of TGF‐β1, and the effects of simvastatin on TGF‐β1‐induced collagen and CTGF production in keloid fibroblasts were determined. The type I collagen, CTGF, and α‐SMA expression levels and the Smad2 and Smad3 phosphorylation levels were assessed by Western blotting. The effect of simvastatin on cell viability was evaluated by assessing the colorimetric conversion of 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide. Simvastatin suppressed TGF‐β1‐induced type I collagen, CTGF, and α‐SMA production in a concentration‐dependent manner. The TGF‐β1‐induced Smad2 and Smad3 phosphorylation levels were abrogated by simvastatin pretreatment. The inhibition of type I collagen, CTGF, and α‐SMA expression by simvastatin was reversed by geranylgeranyl pyrophosphate, suggesting that the simvastatin‐induced cellular responses were due to inhibition of small GTPase Rho involvement. A RhoA activation assay showed that preincubation with simvastatin significantly blocked TGF‐β1‐induced RhoA activation. The Rho‐associated coiled kinase inhibitor Y27632 abrogated TGF‐β1‐induced production of type I collagen, CTGF, and α‐SMA. However, Y27632 had no significant effect on TGF‐β1‐induced phosphorylation of Smad2 and Smad3. In conclusion, the present study suggests that simvastatin is an effective inhibitor of TGF‐β1‐induced type I collagen, CTGF, and α‐SMA production in keloid fibroblasts.     

Hemodynamic and catecholamine responses during tracheal intubation using a lightwand device (Trachlight) in elderly patients with hypertension

Purpose.Tracheal intubation using a lightwand device (Trachlight) should minimize hemodynamic change by avoiding direct-vision laryngoscopy. We evaluated hemodynamic and catecholamine responses during tracheal intubation using a Trachlight in elderly patients with hypertension.Methods.Twenty-six hypertensive patients aged over 65 years undergoing orthopedic surgery were randomly divided into two groups, group L (n = 13) and group T (n = 13). Anesthesia was induced with fentanyl (2g·kg^–1) and propofol (1.5mg·kg^–1), and then muscle relaxation was obtained with vecuronium (0.15mg·kg^–1). The trachea was intubated with either a Macintosh laryngoscope (group L) or a Trachlight (group T). Hemodynamics, plasma catecholamine concentrations, and arterial blood gases were measured before the induction of anesthesia (T0), before tracheal intubation (T1), immediately after tracheal intubation (T2), and 3min after tracheal intubation (T3).Results.The intubation time was shorter in group T than in group L (12.6 ± 1.7 vs 23.5 ± 2.9s, mean ± SE; P 0.01). Compared with the preinduction (T0) value, systolic blood pressure (SBP) showed a significant decrease at T1 and T3 in group L and at T1, T2, and T3 in group T. The heart rate (HR) and plasma norepinephrine (NE) concentration showed no change in either group throughout the time course, whereas the plasma epinephrine (E) concentration showed a significant decrease at T2 and T3 in both groups. The mean values of the rate-pressure product (RPP: HR × SBP) were less than 15 000 after tracheal intubation in both groups. There was no significant difference in hemodynamic or catecholamine responses between groups at any point. No patient had ischemic ST-T changes in either group.Conclusion.A lightwand has no advantage over a laryngoscope in terms of hemodynamic and plasma catecholamine responses to tracheal intubation in elderly patients with hypertension, despite a shorter intubation time.     

Biochemical changes in malignant hyperthermia susceptible swine: cyclic AMP,inositol phosphates, α1, β1- and β2-adrenoceptors in skeletal and cardiac muscle

It has been presumed that alteration in the concentrations of second messengers leads to alterations in the function of the ryanodine receptor. Consequently, we have determined the basal content of cyclic AMP and inositol phosphates in skeletal and cardiac muscle of malignant hyperthermia (MH) susceptible (MHS) and healthy normal control (MHN) swine. Since α,- and β-adrenoceptors are linked to these second messenger systems, the densities of α₁,- and β-adrenoceptors were also determined. In skeletal as well as cardiac muscle, a higher basal concentration of almost all of the inositol phosphates was found. Of all inositol phosphates measured, the presumed second messenger inositol 1,4,5-trisphosphate (1,4,5-IP3) was mostly concentrated in both tissues. Each MHS sample contained more 1,4,5,-IP3 than the highest value observed in MHN muscle, indicating that a threshold of 1,4,5-IP3 concentration for determination of MHS or MHN status can be defined. In addition, MHS skeletal muscle contained more cAMP than MHN, whereas there was no difference between MHS and MHN in cardiac muscle. The changes observed in the different inositol phosphate and cAMP contents were not accompanied by an altered α₁,- or β-adrenoceptor density in skeletal or cardiac muscle between MHS and MHN. However, the total number of β-adrenoceptors of MHN and MHS was significantly higher in cardiac (about 80 fmol/mg protein) than skeletal muscles (about 30 fmol/ mg protein). The cardiac muscles revealed about 80% β₁,- and 20% β₂-adrenoceptors, whereas skeletal muscles were characterised by over 95% β₂-adrenoceptors. In conclusion, the present study supports the view that altered second messenger systems and, thereby, altered intracellular calcium regulations are at least in part involved in the modulation and development of MH. Moreover, in addition to the skeletal muscle, multiple other organs, e.g. heart, may be affected in MH.     

Transforming growth factor‐β (TGF‐β) expression is increased in the subsynovial connective tissues of patients with idiopathic carpal tunnel syndrome

Non‐inflammatory fibrosis of the subsynovial connective tissue (SSCT) is a hallmark of carpal tunnel syndrome (CTS). The etiology of this finding and its relationship to the development of CTS remain poorly understood. Recent studies have found that transforming growth factor‐β (TGF‐β) plays a central role in fibrosis. The purpose of this study was to investigate the expression of TGF‐β and connective tissue growth factor (CTGF), a downstream mediator of TGF‐β, in the pathogenesis of CTS. We compared SSCT specimens from 26 idiopathic CTS patients with specimens from 10 human cadaver controls with no previous diagnosis of CTS. Immunohistochemistry was performed to determine levels TGF‐β1, CTGF, collagen 1(Col1) and collagen 3 (Col3) expression. TGF‐β1 (p < 0.01), CTGF (p < 0.01), and Col3 (p < 0.01) were increased in SSCT of CTS patients compared with control tissue. In addition, a strong positive correlation was found between TGF‐β1 and CTGF, (R² = 0.80, p < 0.01) and a moderate positive correlation between Col3 and TGF‐β1 (R² = 0.49, p < 0.01). These finding suggest that there is an increased expression of TGF‐β and CTGF, a TGF‐β regulated protein, and that this TGF‐β activation may be responsible for SSCT fibrosis in CTS patients. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:116–122, 2014.     

Plasma Levels of Cortisol,Progesterone, Oestradiol‐17β and Prostaglandin F2α Metabolite After ACTH (Synacthen Depot®) Administration in Ovariectomized Gilts

In order to elucidate the effect of stress on reproductive hormones, the present study was designed to investigate the effect of adrenocorticotropic hormone (ACTH) on the plasma levels of cortisol, progesterone, oestradiol‐17 β and prostaglandin F_2α metabolite in ovariectomized gilts. Ovariectomy and cannulation of the jugular vein were performed within 1 week of oestrous detection, under general anaesthesia. Approximately 1 week after surgery, two gilts were each administered ACTH (Synacthen Depot®) intravenously, at a dose of 0.01 mg/kg body weight, and one gilt was given saline solution (5 ml). The reverse was performed on the following day. The administration of ACTH was followed by a concomitant elevation of cortisol, progesterone and prostaglandin F_2α metabolite but not of oestradiol‐17β. Peak cortisol, progesterone and prostaglandin F_2α metabolite levels were reached at 80 ± 10.0, 80 ± 10.0 and 46.6 ± 13.3 min after ACTH administration and the durations of the peaks were 181.8 ± 19.8, 308.1 ± 49.7 and 181.8 ± 7.9 min, respectively. The total area under the curve for cortisol, progesterone and prostaglandin F_2α metabolite was significantly higher in the ACTH than in the control group. The present results indicate that during stress, cortisol, progesterone and prostaglandin F_2α levels are elevated while the level of oestradiol‐17β is less affected. It can be concluded that the administration of ACTH to ovariectomized gilts, results in the elevation of cortisol, progesterone and prostaglandin F_2α metabolite but not of oestradiol‐17β.