Total intravenous anaesthesia with sufentanil-midazolam for major abdominal surgery

Haemodynamic and endocrine stress responses were compared during total intravenous anaesthesia with sufentanil and midazolam or fentanyl and midazolam in patients undergoing elective major abdominal surgery. Twenty-two ASA I and II patients were allocated randomly to receive sufentanil (induction 1.5 micrograms kg-1 plus infusion 1.5 micrograms kg-1 h-1) or fentanyl (induction 10 micrograms kg-1 plus infusion 10 micrograms kg-1 h-1) supplemented with 0.15 microgram kg-1 sufentanil or 1 microgram kg-1 fentanyl as necessary. Midazolam was infused to obtain plasma concentrations of 500-600 ng ml-1. Ventilation was with oxygen-enriched air. The opioid infusion was reduced post-operatively by half and benzodiazepine effects were reversed by titration with flumazenil. Mean arterial pressure, heart rate and cardiac index decreased in both groups after induction (cardiac index: sufentanil 4.94 +/- 0.45 to 2.99 +/- 0.18 litre min-1; fentanyl 4.97 +/- 0.45 to 3.71 +/- 0.36 litre min-1), but all returned to baseline during surgery. With sufentanil; mean arterial pressure was lower throughout the study period, and heart rate was lower intra-operatively. Oxygen uptake decreased in both groups after induction (sufentanil 289 +/- 29 to 184 +/- 21 ml min-1; fentanyl 318 +/- 32 to 216 +/- 32 ml min-1) and remained low with sufentanil until flumazenil was given. Adrenaline concentrations increased in both groups but there was no intergroup difference. The median noradrenaline concentration was lower intra-operatively with sufentanil (0.47 nmol litre-1 (range 0.06-6.77)) than with fentanyl (0.73 nmol litre-1 (0.07-4.58)). Cortisol, glucose and lactate concentrations increased in both groups. Bradycardia occurred in four patients with sufentanil and in three with fentanyl. There were two cases of marked thoracic rigidity with sufentanil and one with fentanyl.     

Anesthetic management of a patient with hypertrophic cardiomyopathy using propofol, fentanyl and ketamine

A 59-year-old male with hypertrophic cardiomyopathy was scheduled for resection of a maxillary cyst. Metoprolol was discontinued the day before surgery. Thirty min before anesthesia, meperidine 35 mg was administered intramuscularly. After intravenous administration of midazolam 3 mg, a pulmonary catheter was inserted for monitoring hemodynamic parameters. Anesthesia was induced with propofol 75 mg, fentanyl 0.15 mg and ketamine 75 mg. Anesthesia was maintained with continuous infusion of propofol 5 mg.kg-1.h-1 and ketamine 1 mg.kg-1.h-1. Moreover, fentanyl was added as necessary during surgery. Blood pressure (BP), pulmonary arterial pressure (PA), systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI) were measured using a pulmonary catheter during anesthesia. Since BP decreased after intubation, dopamine 3 micrograms.kg-1.min-1 was administered for 20 min. The hemodynamic state was stable during surgery. However, BP, PA, SVRI and PVRI increased temporally at extubation. His postoperative course was uneventful. In conclusion, total intravenous anesthesia with propofol, fentanyl and ketamine may be useful for anesthetic management of a patient with hypertrophic cardiomyopathy.     

Effects of toborinone on systemic circulation in patients under general anesthesia

Patients with suppressed systemic circulation under general anesthesia received a 20-minute continuous infusion of toborinone at a rate of 5, 10, or 15 micrograms.kg-1.min-1, and the efficacy and safety of the drug were evaluated. Toborinone increased cardiac index (CI) and stroke volume index (SVI) dose-dependently, with significant increases at 10 and 15 micrograms.kg-1.min-1. An increase in CI was observed from 10 minutes after the start of infusion, with a return to the baseline value at 20-30 minutes after the completion of infusion. Toborinone did not affect heart rate at any dose tested, but the drug tended to decrease mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and right atrial pressure. Mean arterial blood pressure tended to decrease after the start of infusion at all doses tested, and was significantly decreased at 20 minutes after the start of infusion at 10 and 15 micrograms.kg-1.min-1. Systemic vascular resistance and pulmonary vascular resistance decreased at all doses tested. T-wave amplitude on electrocardiaogram (ECG) and oxygen partial pressure in arterial blood decreased at 10 and 15 micrograms.kg-1.min-1. Toborinone increases cardiac output and decreases pre-load and after-load with no effects on heart rate, and, therefore, is thought to be a positive inotropic agent useful in the treatment of circulatory insufficiency. Due care should be exercised to monitor blood pressure, ECG, and arterial blood gas parameters of the patients. The effects of toborinone need to be further investigated in patients with complicated cardiac diseases under general anesthesia and in patients with circulatory insufficiency after surgery, including patients following extracorporeal circulation.     

Clonidine for major vascular surgery in hypertensive patients: a double-blind, controlled, randomized study

The utility of clonidine for hypertensive patients presenting for major vascular procedures remains debatable. Twenty-one hypertensive patients presenting for aortic surgery were given clonidine (n = 11) or placebo (n = 10) in a double-blind, randomized manner. Clonidine was administered 6 micrograms/kg per os 120 min before induction of anesthesia and 3 micrograms/kg intravenously (i.v.) over 60 min from aortic declamping to skin closure. Anesthesia was induced with alfentanil 20 micrograms/kg, midazolam, and atracurium and maintained with nitrous oxide 70%, an alfentanil infusion (0.25 microgram.kg-1. min-1), and isoflurane. Anesthetic requirements, circulatory variables, interventions, and isoproterenol dose-response curves (pre- and postoperatively) were determined. Plasma concentrations of clonidine, alfentanil, and vasoactive hormones were measured. When the clonidine group was compared with the placebo group, (a) isoflurane, alfentanil, and midazolam requirements were reduced by 38%, 42%, and 41%, respectively (P = 0.04, 0.03, 0.0002, respectively); (b) supplemental circulatory and anesthetic adjustments were reduced by 51% (P = 0.0006); (c) interventions with vasopressors were not significantly increased (placebo: two; clonidine: five); (d) systolic and mean arterial pressures and heart rate were reduced; (e) increases in norepinephrine, epinephrine, and plasma renin activity were suppressed, whereas vasopressin surge was attenuated; and (f) chronotropic response to isoproterenol was unaffected. Clonidine was effective in reducing anesthetic requirements and in improving circulatory stability in hypertensive patients presenting for major vascular procedures.     

Vasodilation with adenosine or sodium nitroprusside after coronary artery bypass surgery: a comparative study on myocardial blood flow and metabolism

The effects of adenosine and sodium nitroprusside (SNP) on central hemodynamics and myocardial blood flow and metabolism were investigated postoperatively after elective coronary artery bypass (CABG) surgery in ten sedated and mechanically ventilated patients in the intensive care unit. During three consecutive 15-min periods, SNP (0.8 +/- 0.1 micrograms.kg-1 x min-1), adenosine (88.9 +/- 13.3 micrograms.kg-1 x min-1), and then again SNP (0.7 +/- 0.1 micrograms.kg-1 x min-1) were infused to control postoperative hypertension at a mean arterial pressure of approximately 80 mm Hg. Systemic and pulmonary hemodynamics and global (coronary sinus flow, CSF) as well as regional (great cardiac vein flow, GCVF) myocardial blood flow and metabolic variables were measured. During adenosine infusion, in comparison to SNP, heart rate was unchanged, stroke volume index and cardiac index increased (24% and 32%, respectively), and the systemic vascular resistance index decreased (-26%). Mean pulmonary arterial pressure (24%) as well as pulmonary capillary wedge pressure (27%) and central venous pressure (18%) were higher with adenosine compared to SNP. Adenosine also increased CSF and GCVF (108% and 103%, respectively) without altering the CSF/GCVF flow ratio compared to SNP. Furthermore, adenosine increased the coronary oxygen content (51%) and decreased the arterio-great cardiac vein oxygen content difference (-48%) without changing regional myocardial oxygen consumption, indicating a more pronounced hyperkinetic myocardial circulation compared to SNP. In addition, adenosine infusion decreased arterial PO2 (-11%) and increased the intrapulmonary shunt fraction (57%). The PR interval time of the electrocardiogram was prolonged (12%) and the ST segment was more depressed during adenosine infusion compared to SNP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tumour cell killing using chemically engineered antibody constructs specific for tumour cells and the complement inhibitor CD59

BACKGROUND: Although beta blockers have been used primarily to decrease unwanted perioperative hemodynamic responses, the sedative properties of these compounds might decrease anesthetic requirements. This study was designed to determine whether esmolol, a short-acting beta 1-receptor antagonist, could reduce the propofol concentration required to prevent movement at skin incision. METHODS: Sixty consenting patients were premedicated with morphine, and then propofol was delivered by computer-assisted continuous infusion along with 60% nitrous oxide. Patients were randomly divided into three groups, propofol alone, propofol plus low-dose esmolol (bolus of 0.5 mg/kg, then 50 micrograms.kg-1.min-1), and propofol plus high-dose esmolol (bolus of 1 mg/kg, then 250 micrograms.kg-1.min-1). Two venous blood samples were drawn at equilibrium. The serum propofol concentration that prevented movement to incision in 50% of patients (Cp50) was calculated by logistic regression. RESULTS: The propofol Cp50 with nitrous oxide was 3.85 micrograms/ ml. High-dose esmolol infusion was associated with a significant reduction in the Cp50 to 2.80 micrograms/ml (P < 0.04). Propofol computer-assisted continuous infusion produced stable serum concentrations with a slight positive blas. Esmolol did not alter the serum propofol concentration. No intergroup differences in heart rate or blood pressure response to intubation or incision were found. CONCLUSIONS: Esmolol significantly decreased the anesthetic requirement for skin incision. The components and mechanism of this interaction remain unclear. A simple pharmacokinetic interaction between esmolol and propofol does not explain the Cp50 reduction. These results demonstrate an anesthetic-sparing effect of a beta-adrenergic antagonist in humans under clinically relevant conditions.     

Is patient-controlled sedation good for elderly patients?

The purpose of this study was to evaluate the safety and advantage of intra-operative patient-controlled sedation (PCS) in elderly patients. Propofol PCS was compared with anesthesiologist-controlled sedation (ACS) during knee arthroplasty under epidural anesthesia. Eleven elderly patients scheduled for unilateral knee total or partial arthroplasty were divided randomly into PCS group (n = 6) and ACS group (n = 5). Epidural anesthesia was performed to produce an appropriate level of sensory block (T 10 through S). Firstly a mixture of pentazocine 0.2 mg.kg-1 and 2% mepivacaine 6-9 ml was injected to the epidural space, and anaesthesia was maintained using 2% mepivacaine afterward. Patients in both groups received propofol 0.3 mg.kg-1 i.v. as a loading dose and 0.6 mg.kg-1.h-1 continuous infusion. Furthermore patients in PCS group received propofol PCS (bolus: 0.2 mg.kg-1, lockout time: 3 min). Patients in ACS group were administered propofol continuously and infusion rates were regulated to maintain a sedation score 3 (Wilson et al) by anesthesiologist. Respiratory rate, blood pressure, heart rate, SpO2, arterial blood gas analysis and plasma levels of propofol were measured 4 times during and after the surgery. Satisfaction of patients and surgeons was questioned. Patients in PCS group received a mean propofol dose of 1.9 +/- 0.1 mg.kg-1 during procedures with a mean duration of 147 min. On the other hand patients in ACS group received propofol 2.9 +/- 0.3 mg.kg-1 with 142 min of procedures. Satisfaction of patients and surgeons, the incidence of complication were similar between the groups. For elderly patients who undergo epidural anesthesia, PCS is a safe and effective technique providing similar good sedation as with ACS.     

Comparison of remifentanil in combination with isoflurane or propofol for short-stay surgical procedures

There are few data in the literature that describe the use of remifentanil when administered as a component of an inhalation or total i.v. anaesthetic (TIVA) technique. We studied 251 male and female patients, aged 18-75 years, ASA I-II, undergoing inguinal hernia repair, arthroscopic knee surgery or varicose vein surgery of at least 30 min duration without premedication. Patients were randomized to receive a remifentanil loading dose of 1.0 microgram kg-1 followed by a continuous infusion of 0.5 microgram kg-1 min-1 in combination with isoflurane (end-tidal concentration 0.6%), (Group I, n = 115) or propofol (initial infusion rate 9 mg kg-1 h-1 reduced to 6 mg kg-1 h-1 after 10 min), (Group P, n = 118). The remifentanil infusion rate was reduced by 50%, 5 min after tracheal intubation. Intraoperative stresses were treated with a remifentanil bolus (1 microgram kg-1) followed by an increase in the remifentanil infusion rate. At the insertion of the last suture, the remifentanil infusion and concomitant anaesthetic were switched off simultaneously. Times to spontaneous respiration, adequate respiration and tracheal extubation were significantly shorter in group I compared with group P (6.4 min vs 7.6 min, P < 0.01; 7.6 min vs 9.3, P < 0.003; 7.8 min vs 9.5 min, P < 0.015). Overall mean systolic blood pressures during surgery were greater in group P compared with group I (P < 0.05) but the absolute differences were clinically insignificant (4-5 mm Hg).     

Effects of loprinone hydrochloride on hemodynamics and respiratory oxygenation in patients after cardiac surgery

Loprinone hydrochloride (Lop), a phosphodiesterase fraction III inhibitor and positive inotrope, was recently released in Japan. We evaluated its dose-related effects on hemodynamics and oxygenation as as well as on plasma levels of Lop in ten patients after cardiac surgery. Immediately after admission to the intensive care unit, baseline hemodynamics and arterial blood gas data were obtained; patients with inotropic support, were given 0.1, 0.2, 0.3 microgram.kg-1.min-1.lop over 1 hour incrementally, and additional data were obtained. CI increased significantly from baseline (2.1 +/- 0.3 l.min-1.m-2) to 3.2 +/- 0.8 at 0.3 microgram.kg-1.min-1. Systemic vascular resistance decreased significantly from baseline (2853 +/- 439 dynes.sec.cm-5.m-2) to 1554 +/- 440 at 0.3 micrograms. kg-1.min-1, and mean arterial pressure also decreased significantly from baseline. There were no significant changes in heart rate (HR), central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP), or PaO2.FIO2(-1) in patients over the period evaluated. Plasma levels of Lop rapidly increased to 27.8 ng.ml-1 (effective level; 20 ng.ml-1) at 0.3 microgram.kg-1.min-1. In this study, Lop was shown to effectively increase CI in patients after cardiac surgery with no significant changes in HR, CVP, PAOP or PaO2/FIO2. Thus, Lop has a beneficial effect in the treatment of patients with low cardiac output immediately after cardiac surgery.     

Use of Diprivan for digestive system endoscopy

After evaluation of the patient's clinical condition and appropriate premedication is seems reasonable to suggest for: 1. Endoscopic procedures involving the gastro-intestinal tract: slow, titrated induction, using 0.5 to 1 mg.kg-1 of propofol, until the required level of sedation has been achieved; this may or not be preceded by the injection of a low dose of midazolam (0.02 to 0.03 mg.kg-1) or of alfentanil (5 micrograms.kg-1); maintenance is achieved by bolus injections of 20 mg (up to 0.5 mg.kg-1); maintenance of spontaneous ventilation, with oxygen administration is the rule; SpO2 is monitored routinely; anaesthesia has to be performed according to the recommendations of the French Society of Anaesthesia and Intensive Care (SFAR) and the anaesthetist must be prepared to manage any incident during the endoscopy and the recovery period. 2. Procedures involving the biliary tract and the oesophagus, which require deeper anaesthesia: induction should again be titrated using a very slow infusion, with doses ranging from 0.9 to 2.2 mg.kg-1); the maintenance requires a continuous infusion, doses ranging from 4 to 6 mg.kg-1.h-1 when propofol is administered alone and from 4 to 12 mg.kg-1.h-1 when combined with an opioid; continuous oxygenation is necessary using a nasal airway; the need for intubation depends on the type of procedure and the status of the patient; the same monitoring devices and similar safety measures are required during and after procedure as for any anaesthetic or sedation, especially when it is performed in day-case patients or outside the operating theatre.     

Clonidine and lidocaine inhibition of isoflurane-induced tachycardia in humans

BACKGROUND: A rapid increase in isoflurane concentration can induce tachycardia and hypertension and increase plasma catecholamine concentrations. To investigate a possible mechanism, we measured hemodynamic responses to isoflurane administered via mask; we also administered clonidine for premedication, lidocaine topically to the nasal mucosa, or lidocaine intravenously to evaluate the effect of these drugs on the hemodynamic responses. METHODS: Forty ASA physical status 1 patients (aged 20-30 yr) scheduled for elective oral surgery participated in the study. Thirty patients were randomly allocated to one of three groups: a control group, a group receiving 3-4 micrograms.kg-1 of oral clonidine for premedication, and a group receiving 2 ml of 4% lidocaine spray to the nasal mucosa. Ten patients were assigned nonrandomly to a group receiving intravenous lidocaine continuously (0.4 mg.kg-1 bolus followed by 30 micrograms.kg-1.min-1) after the initial randomized experiments were done to test whether systemic lidocaine blunts the responses to inhaled isoflurane. Anesthesia was induced with thiamylal, after which inhalation of 1% isoflurane in 100% oxygen via mask was begun. The inspired concentration of isoflurane was increased by 1% every 5 min to a maximum of 4%. During normocapnia and without surgical stimulation, heart rate and systolic blood pressure were measured every minute for 20 min before and during isoflurane inhalation. Plasma catecholamine concentrations were measured before and at each isoflurane concentration. RESULTS: In the control and intravenous lidocaine groups, an increase in isoflurane concentration from 2% to 3% significantly increased systolic blood pressure (peak changes of 16 +/- 5 and 15 +/- 6 mmHg, respectively) and heart rate (peak changes of 23 +/- 3 and 13 +/- 4 beats.min-1, respectively). A change in concentration to 4%, however, did not significantly alter hemodynamics. Blood pressure and heart rate responses to a change to 3% isoflurane were significantly blunted in the groups receiving clonidine (peak changes of 4 +/- 4 mmHg and 8 +/- 3 beats.min-1, respectively) or nasal lidocaine (peak changes of 2 +/- 1 mmHg and 4 +/- 2 beats.min-1, respectively) compared with the control group. In all groups, plasma epinephrine and norepinephrine concentrations increased after administration of 2% and 1% isoflurane, respectively. Plasma lidocaine concentrations were 0.3-1.3 micrograms.kg-1 in the nasal lidocaine group and 0.6-1.5 micrograms.kg-1 in the intravenous lidocaine group. CONCLUSIONS: Stepwise increases in isoflurane concentration elicited hypertension and tachycardia as well as increments in plasma catecholamine concentrations during mask anesthesia. Nasal administration of lidocaine and clonidine premedication significantly blunted the circulatory responses to isoflurane. Intravenous lidocaine did not significantly weaken the responses to changes in isoflurane concentration.     

Midazolam for caudal analgesia in children: comparison with caudal bupivacaine

In a randomized, double-blind study we have examined the analgesic efficacy of caudal administration of midazolam, bupivacaine, or a mixture of both drugs in 45 children, undergoing inguinal herniotomy. They were allocated randomly into three groups (n = 15 in each) to receive a caudal injection of either 0.25% bupivacaine 1 ml.kg-1 with or without midazolam 50 micrograms.kg-1 or midazolam 50 micrograms.kg-1 with normal saline 1 ml.kg-1. There were no differences in quality of pain relief, postoperative behaviour or analgesic requirements between the midazolam group and the other two groups. Times to first analgesic administration (paracetamol suppositories) were longer (P < 0.001) in the bupivacaine-midazolam group than in the other two groups. Further, the bupivacaine-midazolam group received fewer (P < 0.05) doses of paracetamol than the bupivacaine group. Side effects such as motor weakness, respiratory depression or prolonged sedation were not observed in patients who received caudal epidural midazolam only. We conclude that caudal midazolam in a dose of 50 micrograms.kg-1 provides equivalent analgesia to bupivacaine 0.25%, when administered postoperatively in a volume of 1 ml.kg-1 for children following unilateral inguinal herniotomy.     

Consequences of electroencephalographic-suppressive doses of propofol in conjunction with deep hypothermic circulatory arrest

BACKGROUND: Some patients who undergo cerebral aneurysm surgery require cardiopulmonary bypass and deep hypothermic circulatory arrest. During bypass, these patients often are given large doses of a supplemental anesthetic agent in the hope that additional cerebral protection will be provided. Pharmacologic brain protection, however, has been associated with undesirable side effects. These side effects were evaluated in patients who received large doses of propofol. METHODS: Thirteen neurosurgical patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest to facilitate clip application to a giant or otherwise high-risk cerebral aneurysm. Electroencephalographic burst suppression was established before bypass with an infusion of propofol, and the infusion was continued until the end of surgery. Hemodynamic and echocardiographic measurements were made before and during the prebypass propofol infusion and again after bypass. Emergence time also was determined. RESULTS: Prebypass propofol at 243 +/- 57 micrograms.kg-1.min-1 decreased vascular resistance from 34 +/- 8 to 27 +/- 8 units without changing heart rate, arterial or filling pressures, cardiac index, stroke volume, or ejection fraction. Propofol blood concentration was 8 +/- 2 micrograms/ml. Myocardial wall motion appeared hyperdynamic at the end of cardiopulmonary bypass, and all patients were weaned therefrom without inotropic support. After bypass, vascular resistance decreased further, and cardiovascular performance was improved compared to baseline values. Nine of the 13 patients emerged from anesthesia and were able to follow commands at 3.1 +/- 1.4 h. Three others had strokes and a fourth had cerebral swelling. CONCLUSIONS: Propofol infused at a rate sufficient to suppress the electroencephalogram does not depress the heart or excessively prolong emergence from anesthesia after cardiopulmonary bypass and deep hypothermic circulatory arrest.     

Pharmacokinetics of intravenous milrinone in patients undergoing cardiac surgery

BACKGROUND: Milrinone is a phosphodiesterase inhibitor with positive inotropic and vasodilator effects that are useful in the treatment of ventricular dysfunction after cardiac surgery. However, the pharmacokinetics of the drug have been investigated only in healthy volunteers and in patients with chronic congestive heart failure. This study investigates the pharmacokinetics of milrinone in adult cardiac surgical patients after cardiopulmonary bypass. METHODS: Milrinone was administered to 25 patients just before or immediately after separation from cardiopulmonary bypass. Arterial blood was sampled over the next 16 h and milrinone plasma concentrations were determined by high-performance liquid chromatography. Data were analyzed by extended nonlinear least-squares regression. The relation between milrinone plasma concentration and hemodynamic effect was examined in an additional 11 patients who had cardiac indices less than 2.5 l.min-1.m-2 immediately after separation from cardiopulmonary bypass. Milrinone was administered and plasma concentrations were related to changes in cardiac index during the next 10 min. RESULTS: A milrinone dose of 50 micrograms/kg in conjunction with an infusion of 0.5 micrograms.kg-1.min-1 consistently maintained plasma concentrations in excess of 100 ng/ml. A triexponential equation describing the plasma concentration as a function of time was used to describe the data. Central-compartment volume was 102 ml/kg, volume of distribution was 1,698 ml/kg, and elimination clearance was 1.88 ml.kg-1.min-1. Pharmacokinetic parameters were independent of dose. The relation between plasma concentration and percentage increase in cardiac index could be described by a sigmoidal curve with the plasma concentration associated with a 50% increase in cardiac index equal to 167 ng/ml. CONCLUSIONS: A milrinone dose of 50 micrograms/kg with an infusion at 0.5 micrograms.kg-1.min-1 maintains plasma concentrations at or above the threshold of therapeutic effects.     

Effects of premedication on dose requirements for propofol: comparison of clonidine and hydroxyzine

The influence of a single dose of clonidine (5 micrograms kg-1) or hydroxyzine (1 mg kg-1) on intraoperative propofol requirements was determined in 28 male patients (ASA I) undergoing elective orthopaedic surgery. Patients were randomly allocated to receive either clonidine or hydroxyzine orally 2 h before induction of anaesthesia. After a loading dose of propofol (2.5 mg kg-1), mivacurium (0.2 mg kg-1) and alfentanil (15 micrograms kg-1), anaesthesia was maintained with a standardized propofol infusion supplemented with nitrous oxide (66%) in oxygen. During surgery, additional propofol boluses (1 mg kg-1) were administered when heart rate or mean arterial pressure increased by more than 10% compared with preinduction values. The clonidine group demonstrated a 14.5% decrease in total propofol requirements (P < 0.05) and a 52.2% reduction in additional propofol boluses (P < 0.02) in comparison with the hydroxyzine group. intraoperative heart rate and mean arterial pressure were significantly lower in the clonidine group but no patients needed treatment with ephedrine for hypotension or bradycardia. Recovery of psychomotor function and discharge from the recovery room were not delayed in the clonidine group. This study indicates that 5 micrograms kg-1 clonidine given as premedication in ASA I patients reduces intraoperative propofol requirements in comparison with 1 mg kg-1 hydroxyzine without inducing adverse effects on recovery or haemodynamic stability.     

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.     

Effects of human atrial natriuretic peptide on hemodynamics and pulmonary gas exchanges in cardiac surgery patients

We investigated the effects of human atrial natriuretic peptide (hANP) on hemodynamics and pulmonary gas exchanges in 22 cardiac surgery patients without pulmonary hypertension. In 10 patients, hANP was infused at a rate of 0.2 microgram.kg-1.min-1 throughout the surgery (hANP group), while in other 12 patients hANP was not infused at all (control group). Before cardiopulmonary bypass (CPB), mean arterial pressure and systemic vascular resistance decreased and cardiac output increased significantly in hANP group as compared with those in control group. After weaning from CPB and at the completion of surgery there was no significant difference in these hemodynamic variables between the two groups. Mean pulmonary arterial pressure, pulmonary vascular resistance, arterial pH, arterial oxygen tension, arterial carbon dioxide tension and shunt ratio did not show any significant difference between the two groups throughout surgery. These findings indicate that hANP infusion causes greater systemic vasodilation with less pulmonary vasodilation, and suggest that this systemic vasodilating effect contributes to the improvement of left ventricular function in patients undergoing open heart surgery.     

Lewis (FUT3) genotypes in two different Chinese populations

BACKGROUND: In our animal study, it was revealed that diadenosine tetraphosphate (Ap4A:F-1500) has a dose-dependent hypotension effect of up to 60% decrease in mean arterial pressure compared to control value. Furthermore, in healthy male volunteers, the safety of Ap4A up to 4 mg.min-1 was confirmed. In patients who require surgical procedures under general anesthesia together with controlled hypotension, hypotension was induced by Ap4A in order to examine its hypotensive effect and modulating action on the blood pressure. METHODS: Ten patients who required controlled hypotension and who were scheduled for elective surgery under general anesthesia were studied. Anesthesia was maintained with isoflurane (n = 7) or sevoflurane (n = 3) in oxygen-nitrous oxide. Controlled hypotension was induced by Ap4A administered at a rate of 10-20 micrograms.kg-1.min-1. The dose was adjusted at a maximum rate of 80 micrograms.kg-1.min-1 until the target blood pressure was achieved. Arterial blood pressure and heart rate were monitored. Arterial samples were drawn at 4 separate time points to measure the concentration of Ap4A in the plasma. RESULTS: The time required for attaining the target blood pressure after initiation of Ap4A infusion was about 16 min, and the time lapse between withdrawal of infusion to recovery of blood pressure was about 18 min. No reflex tachycardia was observed during infusion of Ap4A and no rebound hypertension was evident after withdrawal. The plasma Ap4A concentration increased in response to the acceleration rate of Ap4A administration with a tendency of augmented hypotensive effect. CONCLUSION: As it produces an excellent hypotensive effect together with a modulating action on blood pressure, Ap4A was assessed as useful in producing controlled hypotension.     

Temperament and personality features in panic disorder with or without comorbid mood disorders

We treated a patient with a 30-year history of ethanol and benzodiazepine abuse who, on emerging from general anesthesia, was combative and confused. Our working diagnosis was acute ethanol withdrawal, and the patient received intravenous (i.v.) propofol, and midazolam. Initially small doses (10 to 20 mg) of propofol, combined with a midazolam infusion (50 mg/hr), produced sedation. Later, however, the patient became increasingly combative, confused, hypertensive, and tachycardic despite an i.v. propofol infusion at doses up to 1,000 micrograms/kg/min (total propofol dose: 1,755 mg). Immediate sedation was produced by thiopental bolus (500 mg) and i.v. infusion (200 mg/hr). The implication of the patient's initial appropriate response to propofol, followed by the lack of effect when much higher doses were employed, is discussed. While tachyphylaxis has been reported after long-term propofol use, we believe this to be the first case of acute tachyphylaxis.     

Transmucosal, oral controlled-release, and transdermal drug administration in human subjects: a crossover study with melatonin

PURPOSE: Midazolam has been used clinically as a sedative and as an anaesthetic induction agent. However, the bronchodilating effects of midazolam have not been comprehensively evaluated. We sought to determine relaxant effects of midazolam on the airway. METHODS: After our Animal Care Committee approved the study, eight mongrel dogs were anaesthetized with 30 mg.kg-1 pentobarbitone iv, and were paralysed with 200 micrograms.kg-1.hr-1 pancuronium. The trachea was intubated with an endotracheal tube (ID 7 mm) that had a second lumen for insertion of a superfine fibreoptic bronchoscope (OD 2.2 mm) to measure the bronchial cross-sectional area (BCA) continuously. The tip of the bronchoscope was placed at the level of the second or third bronchial bifurcation of the right bronchus. A videoprinter printed the BCA which was then measured with a NIH image program. Bronchoconstriction was produced with histamine (H) 10 micrograms.kg-1 followed by 500 micrograms.kg-1.hr-1. Thirty minutes later, 0 [saline], 0.01, 0.1 and 1.0 mg.kg-1 midazolam and 25 micrograms.kg-1 flumazenil were given. The BCA was assessed before (basal area) and 30 min after the start of H infusion, and was also measured five minutes after each midazolam and flumazenil iv. At the same time, arterial blood was sampled for plasma catecholamine measurement. RESULTS: Histamine infusion decreased BCA to 49.7 +/- 17.3% of basal BCA. More than 0.1 mg.kg-1 midazolam increased BCA up to 71.7 +/- 15.3% of the basal (1.0 mg.kg-1) (P < 0.01). Plasma adrenaline concentration was decreased from 6.9 +/- 3.8 to 3.7 +/- 1.9 ng.ml-1 by 1.0 mg.kg-1 midazolam (P < 0.05). Flumazenil did not antagonize the relaxant effect of midazolam but reversed the inhibitory effect of midazolam on histamine-induced adrenaline release. CONCLUSION: Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil.