Relation between impedance and electrode temperature during radiofrequency catheter ablation of accessory pathways and atrioventricular nodal reentrant tachycardia

OBJECTIVES: To evaluate and compare the clinical efficacy, impact on hemodynamics, safety profiles, and cost of combined administration of propofol and midazolam (synergistic sedation) vs. midazolam and propofol administered as sole agents, for sedation of mechanically ventilated patients after coronary artery bypass grafting. DESIGN: Prospective, controlled, randomized, double-blind clinical trial. SETTING: Intensive care unit of SCIAS-Hospital de Barcelona. PATIENTS: Seventy-five mechanically ventilated patients who underwent coronary artery bypass graft surgery under low-dose opioid anesthesia. INTERVENTIONS: According to the double-blind method, patients were randomly assigned to receive propofol (n = 25), midazolam (n = 25), or propofol combined with midazolam (n = 25). Infusion rates were adjusted to stay between 8 and 11 points on Glasgow Coma Score modified by Cook and Palma. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD duration of sedation was 14.4 +/- 1.5 hrs, 14.1 +/- 1.1 hrs, and 14.7 +/- 1.9 hrs for the propofol, midazolam, and synergistic groups, respectively. The induction dose was 0.55 +/- 0.05 mg/kg for propofol as sole agent, 0.05 +/- 0.01 mg/kg for midazolam as sole agent, and 0.22 +/- 0.03 mg/kg for propofol administered in combination with 0.02 +/- 0.00 mg/kg of midazolam (p = .001). The maintenance dose was 1.20 +/- 0.03 mg/kg/hr for propofol as sole agent, 0.08 +/- 0.01 mg/kg/hr for midazolam as sole agent, and 0.50 +/- 0.09 mg/kg/hr for propofol administered in combination with 0.03 +/- 0.01 mg/kg/hr of midazolam (p < .001). All sedative regimens achieved similar efficacy in percentage of hours of adequate sedation (93% for propofol, 88% for midazolam, and 90% for the synergistic group, respectively). After induction, both propofol and midazolam groups had significant decreases in systolic blood pressure, diastolic blood pressure, left atrial pressure, and heart rate. Patients in the synergistic group had significant bradycardia throughout the study, without impairment in other hemodynamic parameters. Patients sedated with propofol or synergistic regimen awoke sooner and could be extubated before those patients sedated with midazolam (0.9 +/- 0.3 hrs and 1.2 +/- 0.6 hrs vs. 2.3 +/- 0.8 hrs, respectively, p = .01). Synergistic sedation produced cost savings of 28% with respect to midazolam and 68% with respect to propofol. CONCLUSIONS: In the study conditions, the new synergistic treatment with propofol and midazolam administered together is an effective and safe alternative for sedation, with some advantages over the conventional regimen with propofol or midazolam administered as sole agents, such as absence of hemodynamic impairment, >68% reduction in maintenance dose, and lower pharmaceutical cost.     

Efficacy and safety of a new protocol for continuous infusion of midazolam and fentanyl and its effects on patient distress during electrophysiological studies

Electrophysiological studies are often distressing for patients. We devised a regime of continuous infusion of midazolam and fentanyl during electrophysiological studies without the presence of a specialist anaesthetist. The effects on key hemodynamic and respiratory variables and level of sedation were evaluated in detail in the first 775 patients. The safety of this practice was evaluated in 1,344 consecutive patients. Doses were calculated according to patients' weight and age. A mean total dose of 26 mg of midazolam and 115 mcg of fentanyl were infused. Satisfactory sedation was achieved in 97% of patients. The mean duration of procedure was 188 +/- 90 minutes. Complete amnesia of the procedure was obtained in 87% of patients. Sedation caused clinically insignificant changes in respiratory rate, oxygen saturation, end-tidal CO2 and blood pressure. There were no major complications related to sedation. Upper airway obstruction, usually minor, occurred in 42% and some restlessness in 20% of sedated patients. The assistance of a specialist anesthetist was required in 0.3% of sedated patients for management of restlessness, hypoventilation, or obstructive sleep apnea. The amount of distress experienced by sedated patients (n = 775) was significantly less compared to a previous series of nonsedated patients (n = 775) undergoing electrophysiological studies (P < 0.001). The degree of distress experienced by patients during electrophysiological studies can be reduced significantly by sedation with intravenous midazolam and fentanyl. Continuous infusion is an efficient, safe, and effective way of administering midazolam and fentanyl.     

Temperature-dependent formation of a conjugate between tris(hydroxymethyl)aminomethane buffer and the malondialdehyde-DNA adduct pyrimidopurinone

OBJECTIVE: To examine the effects of cardiopulmonary bypass (CPB) on total and unbound plasma concentrations of propofol and midazolam when administered by continuous infusion during cardiac surgery. DESIGN: Prospective clinical study. SETTING: University hospital. PARTICIPANTS: Twenty-four adult patients undergoing cardiac surgery. INTERVENTIONS: Patients received either propofol or midazolam to supplement fentanyl anesthesia. Twelve patients received a propofol bolus (1 mg/kg) followed by an infusion of 3 mg/kg/hr. A second group received midazolam, 0.2 mg/kg bolus, followed by an infusion of 0.07 mg/kg/hr. MEASUREMENTS AND MAIN RESULTS: Blood sample were collected from the radial artery cannula at 0, 2, 4, 8, 8, 10, 15, 20 minutes and then every 10 minutes before CPB, at 1, 2, 3, 4, 6, 10, 15, 20 minutes and then each 10 minutes during CPB. On weaning from CPB samples were collected at 0, 5, 10 and 20 minutes. Plasma binding, total and unbound propofol and midazolam concentrations were determined by ultrafiltration and high-pressure liquid chromatography (HPLC). CPB resulted in a fall in total propofol and midazolam plasma concentrations, but the unbound concentrations remained stable. The propofol unbound fraction increased from 0.22 +/- 0.06% to 0.41 +/- 0.17%. The midazolam unbound fraction increased from 5.6 +/- 1.0% to 11.2 +/- 2.1%. CONCLUSIONS: Unbound concentrations of propofol and midazolam are not affected by cardiopulmonary bypass. Total intravenous anesthesia algorithms do not need to be changed to achieve stable unbound plasma concentrations when initiating CPB.     

Effect of intravenous anesthetics on spontaneous and endotoxin-stimulated cytokine response in cultured human whole blood

BACKGROUND: Various anesthetics have been suggested to interfere with the immune system. The ability of leukocytes to express surface receptors and mediators is fundamental to a successful host defense. Therefore, the effects of intravenous anesthetics on cytokine release by leukocytes and expression of surface molecules known to modulate this response were determined. METHODS: Concentration-dependent effects of thiopentone, etomidate, propofol, ketamine, midazolam, and fentanyl on spontaneous and endotoxin (lipopolysaccharide; 1 microg/ml)-stimulated cytokine release were studied in whole blood from volunteers (n = 6) cultured for 25 h. In addition, expression of the lipopolysaccharide-recognition molecule CD14 and the major histocompatibility complex class II molecule human leukocyte locus A system-DR (HLA-DR) on monocytes were assessed using flow cytometry. RESULTS: All anesthetics studied elicited only minor effects on spontaneous cytokine release even at pharmacologic concentrations. However, expression density of CD14 was reduced in the presence of thiopentone, etomidate, and propofol, whereas HLA-DR was unaffected. Lipopolysaccharide-stimulated tumor necrosis factor response was inhibited by thiopentone (12.8% [median]; 7.6-18.8 [25-75 percentile]) of control, and ketamine (46.4% [median]; 44.4-56.4 [25-75 percentile]), at pharmacologic concentrations, whereas it was augmented even in the presence of low concentrations of propofol (172.3% [median]; 120.5-200.7 [25-75 percentile]). Ketamine additionally decreased the concentration of interleukin (IL)-1beta (14.8% [median]; 12.0-18.0 [25-75 percentile]). Release of IL-1 receptor antagonist (IL-1ra) was inhibited by thiopentone, etomidate, and propofol, whereas the same anesthetics increased IL-10 concentration simultaneously. Midazolam and fentanyl did not alter the concentrations of any cytokine. CONCLUSIONS: These results suggest a complex modulation of the cytokine response by the studied anesthetics in cultured whole blood. Although effects on spontaneous cytokine release by leukocytes were negligible, some anesthetics affected their ability to respond to lipopolysaccharide.     

Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam

The purpose of this study was to model pharmacodynamically the reversal of midazolam sedation with flumazenil. Ten human volunteers underwent four different sessions. In session 1, individual midazolam pharmacokinetics and electroencephalographic pharmacodynamics were determined. In sessions 2 and 3, a computer-controlled infusion of midazolam with individual volunteer pharmacokinetic data was administered, targeting a plasma concentration corresponding to a light or deep level of sedation (20% or 80% of the maximal midazolam electroencephalographic effect) for a period of 210 minutes. After obtaining a stable electroencephalographic effect and constant midazolam plasma concentrations, a zero-order infusion of flumazenil was started until complete reversal of midazolam electroencephalographic effect was obtained. The flumazenil infusion was then stopped and the volunteer was allowed to resedate because of the constant midazolam drug effect. The electroencephalographic response was measured during a 180-minute period and analyzed by aperiodic analysis and fast-Fourier transforms. In session 4, a midazolam plasma concentration corresponding to a deep level of sedation was targeted for 210 minutes to examine for the possible development of acute tolerance. No flumazenil was given in session 4. For a light sedation level, with a mean midazolam plasma concentration of 160 +/- 64 ng/ml, the mean half-life of the equilibration rate constant of flumazenil reversal is 5.0 +/- 2.5 minutes, and the mean effect site concentration causing 50% of Emax is 13.7 +/- 5.8 ng/ml. For a deep level of sedation, with a mean midazolam plasma concentration of 551 +/- 196 ng/ml, the mean half-life of the equilibration rate constant is 3.9 +/- 1.5 minutes, and the mean effect site concentration causing 50% of Emax is 20.6 +/- 6.8 ng/ml. This study provides an estimate of the magnitude of the blood/central nervous system equilibration delay for flumazenil antagonism of midazolam sedation and further defines the usefulness of the electroencephalogram as a measure of midazolam pharmacodynamic effect.     

Sedation in intensive care units. Indications and techniques

Sedation is a technique widely used in intensive care unit patients. The main objective is to ensure a proper level of analgesia and the best physical and psychical comfort possible. For the vast majority of patients a light level of sedation is adequate and the level of sedation can easily be deepened to perform a short but painful procedure. A deeper level of sedation, close to that of a general anesthesia is rarely needed and limited to specific indications: adult respiratory distress syndrome, head trauma, status asthmaticus. Drugs used for sedation are combinations of opioids (fentanyl or sufentanil), benzodiazepines (midazolam) and hypnotic drugs such as propofol. In combination with the pharmacological approach, a psychological approach is of greater interest in conscious patients.     

Antiemetic activity of propofol after sevoflurane and desflurane anesthesia for outpatient laparoscopic cholecystectomy

BACKGROUND: Controversy exists regarding the effectiveness of propofol to prevent postoperative nausea and vomiting. This prospective, randomized, single-blinded study was designed to evaluate the antiemetic effectiveness of 0.5 mg/kg propofol when administered intravenously after sevoflurane- compared with desflurane-based anesthesia. METHODS: Two hundred fifty female outpatients undergoing laparoscopic cholecystectomy were assigned randomly to one of four treatment groups. All patients were induced with intravenous doses of 2 mg midazolam, 2 microg/kg fentanyl, and 2 mg/kg propofol and maintained with either 1-4% sevoflurane (groups 1 and 2) or 2-8% desflurane (groups 3 and 4) in combination with 65% nitrous oxide in oxygen. At skin closure, patients in groups 1 and 3 were administered 5 ml intravenous saline, and patients in groups 2 and 4 were administered 0.5 mg/kg propofol intravenously. Recovery times were recorded from discontinuation of anesthesia to awakening, orientation, and readiness to be released home. Postoperative nausea and vomiting and requests for antiemetic rescue medication were evaluated during the first 24 h after surgery. RESULTS: Propofol, in an intravenous dose of 0.5 mg/kg, administered at the end of a sevoflurane-nitrous oxide or desflurane-nitrous oxide anesthetic prolonged the times to awakening and orientation by 40-80% and 25-30%, respectively. In group 2 (compared with groups 1, 3, and 4), the incidences of emesis (22% compared with 47%, 53%, and 47%) and requests for antiemetic rescue medication (19% compared with 42%, 50%, and 47%) within the first 6 h after surgery were significantly lower, and the time to home-readiness was significantly shorter in duration (216 +/- 50 min vs. 249 +/- 49 min, 260 +/- 88 min, and 254 +/- 72 min, respectively). CONCLUSIONS: A subhypnotic intravenous dose of propofol (0.5 mg/kg) administered at the end of outpatient laparoscopic cholecystectomy procedures was more effective in preventing postoperative nausea and vomiting after a sevoflurane-based (compared with a desflurane-based) anesthetic.     

Differential effects of etomidate, propofol, and midazolam on calcium and potassium channel currents in canine myocardial cells

BACKGROUND: Intravenous anesthetics etomidate, propofol, and midazolam produce negative inotropic effects of various degrees. The mechanism underlying these differences is largely unknown. METHODS: The effects of intravenous anesthetics on L-type Ca2+, transient outward and inward-rectifier K+ channel currents (ICa, IKto, and IK1) were compared in canine ventricular cells using the whole-cell voltage-clamp technique. ICa and IK were elicited by progressively depolarizing cells from -40 to +40 mV, and from -90 to +60 mV, respectively. The peak amplitude and time-dependent inactivation rate of ICa and IK were measured before, during, and after the administration of equimolar concentrations (5, 30, or 60 microM) of etomidate, propofol, or midazolam. RESULTS: Exposure to etomidate, propofol, and midazolam produced a concentration-dependent inhibition of ICa. Midazolam was the most potent intravenous anesthetic; at 60 microM, etomidate, propofol, and midazolam decreased peak ICa by 16 +/- 4% (mean +/- SEM), 33 +/- 5%, and 47 +/- 5%, respectively. Etomidate, propofol, and midazolam given in a 60-microM concentration decreased IKto by 8 +/- 3%, 9 +/- 2%, and 23 +/- 3%, respectively. IK1 was decreased by 60 microM etomidate and midazolam by 20 +/- 6% and 14% +/- 5%, respectively. Propofol had no effect on IK1. CONCLUSIONS: At equimolar concentrations, intravenous anesthetics decreased the peak ICa, IKto, and IK1 with various degrees of potency. Effects of anesthetics on ICa were significantly greater compared with their effects on K+ currents. These findings suggest that the negative inotropic actions of etomidate, propofol, and midazolam are related, at least in part, to decreased ICa. Some effects, such as IK inhibition, may partially antagonize effects of decreased ICa. Indeed, the final effect of these intravenous anesthetics on myocardium will be the sum of these and other sarcolemmal and intracellular effects.     

Drug retention, efflux, and resistance in tumor cells

This prospective, randomized trial of paediatric surgical outpatients, premedicated with oral midazolam, was designed to determine if an intravenous thiopentone induction of anaesthesia prolongs postoperative recovery compared to an inhalation induction with halothane. One hundred children, one to ten years of age, undergoing ENT surgical procedures of 30-60 min duration received midazolam 0.5 mg.kg-1 with atropine 0.03 mg.kg-1 and were randomized to either halothane (Group 1, n = 50) or a thiopentone induction (Group 2, n = 50) technique, followed by a standardized anaesthetic-protocol. Time to extubation was significantly greater in the thiopentone group (8.8 +/- 4 min vs 7.1 +/- 3 min, P < 0.05). Patients receiving thiopentone were also more sedated than the halothane group on arrival in the PARR (3.9 +/- 1.5, 3.3 +/- 1.7, respectively P < 0.05), but the differences disappeared after 30 min. Children premedicated with oral midazolam who receive an intravenous thiopentone induction have a slightly prolonged emergence from anesthesia compared to children induced with halothane.     

Propofol or midazolam for sedation and early extubation following cardiac surgery

PURPOSE: The purpose of this randomized, double-blind study was to evaluate the efficacy of midazolam and propofol for postoperative sedation and early extubation following cardiac surgery. METHODS: ASA physical status II-III patients scheduled to undergo elective first-time cardiac surgery with an ejection fraction > 45% were eligible. All patients received a standardized sufentanil/isoflurane anaesthesia. During cardiopulmonary bypass 100 micrograms.kg-1.min-1 propofol was substituted for isoflurane. Upon arrival in the Intensive Care Unit (ICU), patients were randomized to either 10 micrograms.kg-1.min-1 propofol (n = 21) or 0.25 microgram.kg-1.min-1 midazolam (n = 20). Infusion rates were adjusted to maintain sedation within a predetermined range (Ramsay 2-4). The infusion was terminated after four hours. Patients were weaned from mechanical ventilation and their tracheas extubated when Haemodynamic stability, haemostasis, normothermia and mental orientation were confirmed. Haemodynamic measurements, arterial blood gas tensions and pulmonary function tests were recorded at specified times. RESULTS: There were no differences between the two groups for the time spent at each level of sedation, number of infusion rate adjustments, amount of analgesic and vasoactive drugs, times to awakening and extubation. The costs of propofol were higher than those of midazolam. There were no differences in haemodynamic values, arterial blood gas tensions and pulmonary function. CONCLUSION: We conclude that midazolam and propofol are safe and effective sedative agents permitting early extubation in this selected cardiac patient population but propofol costs were higher.     

Comparison of tramadol and tramadol/droperidol mixture for patient-controlled analgesia

PURPOSE: To compare the analgesic efficacy and side effects of tramadol vs tramadol and droperidol for post-operative patient-controlled analgesia (PCA). METHODS: Randomised, double-blind study. Thirty-four patients undergoing elective colorectal or head and neck surgery were allocated to Group 1 (n = 18, PCA bolus 10 mg tramadol) or Group 2 (n = 16, PCA bolus 10 mg tramadol + 0.1 mg droperidol). Anaesthesia was induced with fentanyl and thiopentone and maintained with O2, N2O plus enflurane or isoflurane with iv morphine at doses decided by the attending anaesthetists. Muscle relaxation was achieved with atracurium or vecuronium. Patients were observed four-hourly for pain using an 11-point verbal rating scale (VRS). Nausea and vomiting, and sedation were assessed using four-point scales post-operatively. Vital signs, request for rescue anti-emetic and analgesic, and overall satisfaction were recorded. RESULTS: The mean nausea scores were lower in Group 2 (1.00 +/- 1.33 vs 0.06 +/- 0.25 at 0-8 hr, 1.22 +/- 1.93 vs 0.06 +/- 0.25 at 8-16 hr, P < 0.01; 0.81 +/- 1.68 vs 0 at 32-40 hr, P < 0.05; Group 1 vs Group 2). The vomiting scores were also lower (0.50 +/- 1.04 vs 0 at 0-8 hr, 0.67 +/- 1.50 vs 0, at 8-16 hr, P < 0.05; Group 1 vs Group 2). Seven (39%) patients in Group 1, but none in Group 2 requested rescue anti-emetic (P < 0.01). There were no differences in VRS, sedation score, overall satisfaction or vital signs. CONCLUSION: Tramadol and droperidol combination is superior to tramadol alone for post-operative PCA. It provides a similar quality of analgesia with less nausea and vomiting and without an increase in sedation.     

Endocrine stress reaction, hemodynamics and recovery in total intravenous and inhalation anesthesia. Propofol versus isoflurane

This prospective, randomised study compared total intravenous anaesthesia (TIVA) and inhalation anaesthesia with respect to endocrine stress response, haemodynamic reactions, and recovery. METHODS. The investigation included two groups of 20 ASA I-II patients 18-60 years of age scheduled for orthopaedic surgery. For premedication of both groups, 0.1 mg/kg midazolam was injected IM. Patients in the propofol group received TIVA (CPPV, PEEP 5 mbar, air with oxygen FiO2 33%) with propofol (2 mg/kg for induction followed by an infusion of 12-6 mg/kg.h) and fentanyl (0.1 mg before intubation, total dose 0.005 mg/kg before surgery, repetition doses 0.1 mg). For induction of patients in the isoflurane-group, 5 mg/kg thiopentone and 0.1 mg fentanyl was administered. Inhalation anaesthesia was maintained with 1.2-2.4 vol.% isoflurane in nitrous oxide and oxygen at a ratio of 2:1 (CPPV, PEEP 5 mbar). For intubation of both groups, 2 mg vecuronium and 1.5 mg/kg suxamethonium were injected, followed by a total dose of 0.1 mg/kg vecuronium. Blood samples were taken through a central venous line at eight time points from before induction until 60 min after extubation for analysis of adrenaline, noradrenaline (by HPLC/ECD), antidiuretic hormone (ADH), adrenocorticotropic hormone (ACTH), and cortisol (by RIA). In addition, systolic arterial pressure (SAP) heart rate (HR), arterial oxygen saturation (SpO2), and recovery from anaesthesia were observed. RESULTS. Group mean values are reported; biometric data from both collectives were comparable (Table 1). Plasma levels of adrenaline (52 vs. 79 pg/ml), noradrenaline 146 vs. 217 pg/ml), and cortisol (82 vs. 165 ng/ml) were significantly lower in the propofol group (Table 2, Figs. 1 and 3). Plasma levels of ADH (4.8 vs. 6.1 pg/ml) and ACTH (20 vs. 28 pg/ml) did not differ between the groups (Table 2, Figs 2 and 3). SAP (128 vs. 131 mmHg) was comparable in both groups, HR (68/min vs. 83/min) was significantly lower in the propofol group, and SpO2 (97.1 vs 97.4%) showed no significant difference (Table 3). Recovery from anaesthesia was slightly faster in the propofol group (following of simple orders 1.9 vs. 2.4 min, orientation with respect to person 2.4 vs. 3.4 min, orientation with respect to time and space 2.8 vs. 3.7 min), but differences failed to reach statistical significance. CONCLUSIONS. When compared with isoflurane inhalation anaesthesia, moderation of the endocrine stress response was significantly improved during and after TIVA with propofol and fentanyl. Slightly shorter recovery times did not lead to an increased stress response. With respect to intra- and postoperative stress reduction, significant attenuation of sympatho-adrenergic reaction comparable SAP and reduced HR, sympatholytic and hypodynamic anaesthesia with propofol and fentanyl seems to be advantageous for patients with cardiovascular and metabolic disorders. For this aim, careful induction and application of individual doses is essential.     

General anaesthesia for surgery can influence circulating melatonin during daylight hours

BACKGROUND: Both melatonin and anaesthetics have been shown to affect sleep and behaviour. The effect of general anaesthesia on circulatory melatonin has not been reported, but anaesthetic-related alterations in hormone profiles are known. We hypothesize that differences in recovery from anaesthesia may be associated with differences in circulatory melatonin levels because of melatonin's sedative effect in humans. METHODS: The influences of general anaesthesia and surgery on circulating melatonin, prolactin, and cortisol concentration were investigated in 32 female patients scheduled for elective gynaecological surgery to study differences in hormone profiles and responses during anaesthesia and the recovery period. Patients were randomly assigned to one of two groups. General anaesthesia was induced with either thiopentone/fentanyl (Group 1: n = 16) or propofol/fentanyl (Group 2: n = 16). Maintenance of anaesthesia was achieved with either isoflurane (0.8-1.0 vol%)/fentanyl (Group 1) or propofol (6 mg.kg-1.h-1)/fentanyl (Group 2) with a N2O/O2 flow ratio of 2:1 in both groups. During anaesthesia, patients' eyes were carefully taped shut to prevent light effects. Blood samples were taken before and after premedication, immediately before induction of anaesthesia, every 15 min during anaesthesia, and hourly in the recovery room for 8 h. The control group consisted of 6 healthy women who were not subjected to surgery, but who were in a similar environment, including light conditions, as the study groups. RESULTS: Isoflurane and propofol anaesthesia as well as darkness elicited elevated plasma melatonin levels that persisted in the recovery period in patients anaesthetized with isoflurane, but gradually decreased during the recovery of patients anaesthetized with propofol. Circulating prolactin and cortisol values were also elevated during anaesthesia and had similar decreases during the recovery period. CONCLUSION: Higher plasma levels of melatonin during the recovery period following isoflurane anaesthesia may, in part, explain increased sedation in these patients compared with patients who received propofol anaesthesia. However, the relationship between recovery from anaesthesia and plasma melatonin levels may not be simple and straightforward.     

Thermoregulatory effects of caffeine ingestion during submaximal exercise in men

BACKGROUND: The exclusive effect of caffeine ingestion on exercise thermoregulation is unclear; data indicate that caffeine may have a positive effect, a negative effect, or no effect. METHODS: Rectal (TRE) and mean skin (TSK) temperatures, skin heat conductance (HSK), and sweat rate (MSW) were measured during 30 min of rest and subsequent 70 min of submaximal cycle-ergometer exercise (67% VO2PEAK) in 11 aerobically conditioned men (mean +/- SD 29 +/- 6 yr, 49 +/- 6 mL x min(-1) x kg(-1) VO2PEAK) under two conditions: a caffeine (10 mg x kg(-1) ingestion (CI) session and a noncaffeine ingestion (NCI) control session. RESULTS: There were no significant differences in physiological or thermoregulatory parameters during exercise: X (+/-SE) end exercise levels for the NCI and CI sessions, respectively, were VO2 = 2.50 +/- 0.09 vs. 2.55 +/- 0.09 L x min(-1); heart rate = 145 +/- 7 vs. 145 +/- 5 bpm; HSK = 30 +/- 3 vs. 28 +/- 3 kcal x m(-2) x h(-1) x degrees C(-1); MSW = 393 +/- 35 vs. 378 +/- 36 g x m(-2) x h(-1); and TRE = 38.3 +/- 0.2 vs. 38.4 +/- 0.1 degrees C. Control TSK was lower than that for CI by 0.4 to 0.5 degrees C at rest and during exercise. CONCLUSION: Ingestion of a high level (10 mg x kg(-1) of caffeine has no effect on skin heat conductance, sweating, or the rate of increase and final level of rectal temperature during moderate, submaximal leg exercise.     

Overnight sedation with midazolam or propofol in the ICU: effects on sleep quality, anxiety and depression

OBJECTIVE: To assess and compare the impact of overnight sedation with midazolam or propofol on anxiety and depression levels, as well as sleep quality, in non-intubated patients in intensive care. DESIGN: Open, comparative prospective, randomised study. SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS: 40 conscious patients expected to stay in the ICU for at least 5 days who were admitted following trauma or elective orthopaedic, thoracic or abdominal surgery. MEASUREMENTS AND RESULTS: Evaluation of a self-assessment scale (Hospital Anxiety and Depression Scale, HAD) on the day following the 1st, 3rd and 5th night of sedation with either midazolam or propofol. Heart rate, pulse oximetry and blood gases were monitored. Eight patients were excluded from the analysis. The level of anxiety was severe (HAD > 10) in 31% of the patients receiving midazolam and in 26% (p = 0.1) receiving propofol after the first night of sedation with no significant improvement over the next few days. The levels of depression remained high (> 10) in 54% of patients receiving midazolam, and in 16% of the patients receiving propofol (p = 0.15). Sleep quality tended to improve during the study in the two groups. CONCLUSIONS: These data show that half of the patients in the ICU experienced high levels of anxiety and depression during the first 5 post-operative or post-trauma days in the ICU. The beneficial effects of sedation on sleep quality were comparable for midazolam and propofol, regardless of a lack of improvement in anxiety and depression. However, an improved quality of sleep could help to re-establish a physiological night and day rhythm.     

Age alters regional distribution of blood flow during moderate-intensity exercise

During dynamic exercise in warm environments, requisite increases in skin and active muscle blood flows are supported by increasing cardiac output (Qc) and redistributing flow away from splanchnic and renal circulations. To examine the effect of age on these responses, six young (Y; 26 +/- 2 yr) and six older (O; 64 +/- 2 yr) men performed upright cycle exercise at 35 and 60% of peak O2 consumption (VO2peak) in 22 and 36 degrees C environments. To further isolate age, the two age groups were closely matched for VO2peak, weight, surface area, and body composition. Measurements included heart rate, Qc (CO2 rebreathing), skin blood flow (from increases in forearm blood flow (venous occlusion plethysmography), splanchnic blood flow (indocyanine green dilution), renal blood flow (p-amino-hippurate clearance), and plasma norepinephrine concentration. There were no significant age differences in Qc; however, in both environments the O group maintained Qc at a higher stroke volume and lower heart rate. At 60% VO2peak, forearm blood flow was significantly lower in the O subjects in each environment. Splanchnic blood flow fell (by 12-14% in both groups) at the lower intensity, then decreased to a greater extent at 60% VO2peak in Y than in O subjects (e.g., -45 +/- 2 vs. -33 +/- 3% for the hot environment, P < 0.01). Renal blood flow was lower at rest in the O group, remained relatively constant at 35% VO2peak, then decreased by 20-25% in both groups at 60% VO2peak. At 60% VO2peak, 27 and 37% more total blood flow was redistributed away from these two circulations in the Y than in the O group at 22 and 36 degrees, respectively. It was concluded that the greater increase in skin blood flow in Y subjects is partially supported by a greater redistribution of blood flow away from splanchnic and renal vascular beds.     

Anesthesia in surgery for epilepsy

OBJECTIVES: To evaluate the efficacy of general anesthesia during epileptic surgery. MATERIAL AND METHODS: A retrospective study of 64 patients who received general anesthesia during epileptic surgery. In the preoperative period, anticonvulsive medication was adjusted in accordance with plasma levels and withdrawn entirely 8 hours before surgery. After premedication with droperidol and fentanyl, a balanced anesthetic technique was applied, based on pentothal, pancuronium (or vecuronium), fentanyl, N2O and isoflurane. Continuous monitoring of ECG, arterial blood pressure, pulse oximetry, ET CO2 and neuromuscular function. Isoflurane was stopped for 10 min after the opening of the duramadre so that ECoG could be recorded and methohexital or propofol was given in some cases in order to activate the epileptogenic focus. Muscular relaxation was restored intraoperatively following the study of somatosensory evoked potentials. Immediate and later complications related to anesthesia or surgery were recorded. RESULTS: The surgical procedure performed in most cases was temporal or frontal resection, with a mean duration for anesthesia of 377 +/- 50 min and for surgery of 318 +/- 50 min. Only one patient received local anesthesia and no hemodynamic changes were observed. Perioperative complications were cerebral edema (4 cases), arrhythmia (2 cases) and bronchospasm (1 case). Postoperative complications were as follows: 3 of 9 patients undergoing callosotomy required mechanical ventilation for 24 hours, 4 patients experienced language alterations, 3 wounds were infected, 2 cases of hemiplegia were observed, 1 status epilepticus occurred after administration of propofol and there was 1 case of respiratory distress. Anticonvulsive medication was given parenterally after surgery. CONCLUSIONS: General anesthesia is a safe and effective method for epileptic surgery, with local anesthesia providing additional sedation for isolated cases. Appropriate treatment requires an understanding of the pharmacokinetics and pharmacodynamics of the drugs used, as well as knowledge of the condition and the anticonvulsive medications used.     

Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies

The association of propofol with excitatory motor activity, such as myoclonic jerking and opisthotonus, in humans and in animals suggests that it may aggravate clinical seizure activity in some circumstances, although evidence suggests that under other circumstances, propofol inhibits seizure activity. In the current study, we assessed the effect of sedating doses of propofol on lidocaine-induced seizure activity in spontaneously breathing rats receiving no other anesthetics. Adult Sprague-Dawley male rats, 300-400 g, were divided into a control group and three experimental groups representing three graded levels of propofol sedation. The control rats then received a lidocaine infusion at the rate of 150 mg x kg(-1) x h(-1), resulting in a slow, progressive increase in systemic lidocaine concentrations. At the onset of electroencephalographic (EEG) seizure activity, arterial lidocaine concentrations were obtained. The treated rats received propofol according to three different dose schedules: Dose 1 = 10 mg x kg(-1) x h(-1) after a 2.5-mg/kg bolus; Dose 2 = 20 mg x kg(-1) x h(-1) after a 5-mg/kg bolus; Dose 3 = 40 mg x kg(-1) x h(-1) after a 10-mg/kg bolus. After 30 min, a steady level of sedation, dependent on the dose of propofol, was achieved. The lidocaine infusion was then started, and systemic lidocaine levels were obtained at the onset of EEG seizure activity. The lidocaine was continued until the onset of death by cardiac arrest. Plasma lidocaine was measured by gas chromatography. Analysis of variance and Dunnett's t-test were used for comparisons with the control values. Continuous propofol sedation increased the seizure dose of lidocaine from 37.7 +/- 3.5 mg/kg (mean +/- SEM) to 52.5 +/- 2.6 mg/kg (Dose 1, P < 0.05) and 67.9 +/- 8.6 mg/kg (Dose 2, P < 0.05), and completely abolished lidocaine seizures at Dose 3. The lethal dose of lidocaine, 89.4 +/- 10.5 mg/kg control versus 108.7 +/- 10.3 mg/kg (Dose 1), 98.3 +/- 10.1 mg/kg (Dose 2), and 93.5 +/- 10.4 mg/kg (Dose 3) did not differ among groups. The lidocaine levels at seizure threshold were increased in the propofol-treated rats: 16.9 +/- 0.5 microg/mL control versus 19.2 +/- 0.7 microg/mL (Dose 1, P = not significant) and 23.7 +/- 1.8 microg/mL (Dose 2, P < 0.05). Continuous propofol sedation in spontaneously breathing rats receiving no other anesthetics exerts a protective effect against lidocaine-induced seizures in a monotonic, dose-dependent fashion. The cardiac arrest dose of lidocaine is unaffected by propofol under these conditions. IMPLICATIONS: The i.v. anesthetic drug propofol, given to rats to produce sedation, was found to suppress seizure activity caused by overdosage of the local anesthetic lidocaine.     

Effect of beta-carboline-3-carboxoylate-t-butyl ester on ventilatory control

beta-carboline-3-carboxylate-t-butyl ester (beta CCT) is the most selective antagonist for the alpha 1 beta 2 gamma 2 benzodiazepine (BZ) receptor subtype which blocks anticonvulsant and antipunishment (anxiolytic) but not sedative and myorelaxant effects of diazepam. We sought to determine whether the alpha 1 beta 2 gamma 2 BZ receptor subtype modulates ventilation and whether beta CCT antagonizes respiratory depressant effects of BZ's. Room air (RA) ventilation and the ventilatory response to 6% & 12% CO2 were non-invasively assessed by barometric plethysmography in 30 gm mice, n = 11. Plethysmograph signal amplitude (AMP), respiratory rate (RR) and minute ventilatory effort (MVE = AMP*RR), were measured. Runs were performed pre-drug & after IP injection of saline, vehicle for beta CCT, beta CCT (60mg/kg), midazolam (10mg/kg), and midazolam followed by beta CCT. Compared with pre-drug value, midazolam depressed MVE during RA and CO2 stimulation (% of pre-drug value: RA:57.7 +/- 17.4%, 6% CO2:53.73 +/- 14.3%, 12% CO2:69.1 +/- 26.1%, p < .0001, ANOVA). Subsequent beta CCT partially reversed this depression during RA conditions (72.8 +/- 25.7% of pre-drug value, p < .03 compared with midazolam) and 6% CO2 stimulation (67.1 +/- 10.7% of pre-drug value, p < .006 compared with midazolam) but not with 12% CO2. Thus, the alpha 1 beta 2 gamma 2 BZ receptor subtype modulates ventilation and beta CCT partially antagonizes respiratory depressant effects of BZ's.     

Propofol, but not thiopentone or etomidate, enhances isoflurane-induced coronary vasodilatation in dogs

PURPOSE: To test the hypothesis that thiopentone, propofol, and etomidate alter the coronary vascular effects of abruptly administered isoflurane. METHODS: Dogs (n = 6) received inspired isoflurane 5% in the presence of thiopentone (20 mg.kg-1 induction dose and 20 mg.kg-1.hr-1 infusion), propofol (5 mg.kg-1 induction dose and 40 mg.kg-1.hr-1 infusion), etomidate (2 mg.kg-1 induction dose and 5 mg.kg-1.hr-1 infusion), or isoflurane (1.0 MAC) anaesthesia in a random fashion. Haemodynamics were assessed in the conscious state, during baseline anaesthesia, and at 30 sec intervals for five minutes after beginning isoflurane 5%. RESULTS: Rapidly administered isoflurane caused greater (P < 0.05) reductions in coronary vascular resistance in thiopentone- or propofol--than in isoflurane-anaesthetized dogs. Isoflurane produced greater (P < 0.05) increases in the ratio of coronary blood flow velocity to pressure-work index (an index of myocardial oxygen consumption; +109 +/- 19% during isoflurane alone vs +182 +/- 27% change from baseline during propofol and isoflurane) consistent with relatively greater direct coronary vasodilatation during baseline propofol than during baseline isoflurane anaesthesia. Isoflurane caused larger increases in coronary blood flow velocity in dogs anaesthetized with etomidate concomitant with higher coronary perfusion pressure and pressure-work index than in those anaesthetized with isoflurane alone. CONCLUSIONS: The results suggest that thiopentone, propofol, and etomidate each uniquely modify the coronary vascular responses to abrupt administration of high inspired concentrations of isoflurane in chronically instrumented dogs.