Effect of beta and alpha adrenergic blockade on glucose-induced thermogenesis in man.

After intravenous glucose/insulin infusion there is an increase in oxygen consumption and energy expenditure that has been referred to as thermogenesis. To examine the contribution of the beta and alpha adrenergic nervous system to this thermogenic response, 12 healthy volunteers participated in three studies: (a) euglycemic insulin (plasma insulin approximately 100 microunits/ml) clamp study (n = 12); (b) insulin clamp study after beta adrenergic blockade with intravenous propranolol for 1 h (n = 12); (c) insulin clamp study after alpha adrenergic blockade with phentolamine for 1 h (n = 5). During the control insulin clamp study total glucose uptake, glucose oxidation and nonoxidative glucose uptake averaged 7.85 +/- 0.47, 2.62 +/- 0.22, and 5.23 +/- 0.51 mg/kg X min. After propranolol infusion, insulin-mediated glucose uptake was significantly reduced, 6.89 +/- 0.41 (P less than 0.02). This decrease was primarily the result of a decrease in glucose oxidation (1.97 +/- 0.19 mg/kg X min, P less than 0.01) without any change in nonoxidative glucose metabolism. Phentolamine administration had no effect on total glucose uptake, glucose oxidation, or nonoxidative glucose disposal. The increments in energy expenditure (0.10 +/- 0.01 vs. 0.03 +/- 0.01 kcal/min) and glucose/insulin-induced thermogenesis (4.9 +/- 0.5 vs. 1.5 +/- 0.5%) were reduced by 70% during the propranolol/insulin clamp study. The increments in energy expenditure (0.12 +/- 0.03 kcal/min) and thermogenesis (5.0 +/- 1.5%) were not affected by phentolamine. These results indicate that activation of the beta adrenergic receptor plays an important role in the insulin/glucose-mediated increase in energy expenditure and thermogenesis. In contrast, the alpha adrenergic receptor does not appear to participate in this response.

The effect of selective beta adrenergic blockade on glucose-induced thermogenesis in man.

We have previously shown that the increase in energy expenditure following glucose/insulin infusion is, in large part, mediated by the sympathetic nervous system and that this sympathetic component can be blocked by the nonselective beta-1, beta-2 antagonist propranolol. To examine which beta adrenergic receptor mediates this thermogenic response, we performed euglycemic insulin clamp studies in eight healthy control subjects with and without metoprolol at a dose known to block only the beta-1 adrenergic receptor. Basal glucose oxidation and energy expenditure were similar in the control and metoprolol groups. During the last hour of the insulin clamp study, glucose oxidation (3.06 +/- 0.25 v 2.92 +/- 0.21 mg/kg X min), total body glucose uptake (8.17 +/- 0.70 v 7.13 +/- 0.49 mg/kg X min), and nonoxidative glucose uptake (5.11 +/- 0.60 v 4.21 +/- 0.44 mg/kg X min) were not different in the control compared to the metoprolol group. However, the increment in energy expenditure was inhibited by 64% during metoprolol infusion (0.04 +/- 0.01 v 0.11 +/- 0.02 kcal/min, P less than 0.01). Glucose/insulin-induced thermogenesis was similarly reduced by metoprolol (2.56 +/- 0.81 v 5.04 +/- 0.74%, P less than 0.01). These results are quantitatively quite similar to those observed with propranolol. We conclude that the beta adrenergic nervous system and, specifically, the beta-1 receptor mediates the thermogenic response to glucose/insulin infusion.

Acute pulmonary edema in the post partum and cor triatriatum sinistrum.

A case is described of an apparently healthy young woman in her first pregnancy who presented with acute pulmonary edema in the early postpartum period in the context of mild pregnancy-induced hypertension. After quick improvement in her condition, a Doppler followed by a transesophageal study revealed a left atrial septation with a small atrial septal defect secundum type and moderate mitral regurgitation strongly suggestive of a cor triatriatum sinistrum.

A double-blind, parallel-group, placebo-controlled, dose-ranging, multicenter study of intravenous granisetron in the treatment of postoperative nausea and vomiting in patients undergoing surgery with general anesthesia.

STUDY OBJECTIVE: To compare the effectiveness of granisetron with placebo in the treatment of established postoperative nausea and vomiting (PONV). DESIGN: Randomized, placebo-controlled study. SETTING: 34 hospitals in Europe, Scandinavia, and South Africa. PATIENTS: 519 ASA physical status I, II, and III patients who developed PONV within 4 hours of the end of surgery performed with general anesthesia. INTERVENTIONS: Patients received a single intravenous dose of granisetron 0.1 mg, 1 mg, or 3 mg, or placebo when symptoms of nausea or vomiting were experienced. Additional rescue medication could be given at the investigator's discretion if nausea and vomiting were not controlled. MEASUREMENTS AND MAIN RESULTS: At all doses investigated, granisetron was significantly more effective (p < or = 0.001) than placebo in controlling vomiting: 38%, 46%, and 49% of patients receiving granisetron, 0.1 mg, 1.0 mg, and 3.0 mg, respectively, experienced no vomiting in the first 24 hours following drug administration, compared with 20% receiving placebo. There was a statistically significant linear relationship between vomiting control and granisetron dose (p < 0.001). Survival distributions of time to resolution of vomiting confirmed the statistically significant difference between patients receiving granisetron and those receiving placebo. Granisetron was well tolerated: the most common adverse experiences were pain, constipation, anemia, and headache, and the incidence of adverse experiences was not statistically significantly higher in any of the granisetron groups than in the placebo group. CONCLUSION: Granisetron was significantly more effective than placebo in all groups. Further studies in specific subgroups may be warranted.

[Energy metabolism and craniocerebral injury]. / Métabolisme énergétique et traumatisme crâniocérébral.

Severe head injury induces major hormonal, humoral and metabolic changes, characterized by increases in stress hormone secretion, lymphokines production, associated with high lipid and protein catabolism as well as changes in energy expenditure (EE). Numerous factors influence EE in head-injured patients, particularly anthropometric data, body temperature, nutritional support, level of consciousness, muscular tone and activity. Resting EE is usually increased following brain trauma; however, normal or decreased metabolic rates can be observed in curarized patients on mechanical ventilation or in patients receiving high doses of barbiturates.

[Algorithms for oxygenation and difficult intubations in obstetrics]. / Algorithmes de l'oxygénation et de l'intubation difficiles en obstétrique.

The obstetrical population is prone to difficult or failed intubation. Control of the airway is complicated by several factors specific to obstetric anesthesia; time of apnea is short due to a reduced functional residual capacity, pregnancy-induced hypertension and obesity are relatively frequent; anesthetist's skill can also be mentioned. The best approach to this problem lies in its prevention, using epidural analgesia as soon as possible. Furthermore, the number of difficult intubations can be considerably reduced by a thorough pre-anesthetic examine. Each anesthetist must keep an algorithm in mind, should a difficult or failed intubation in obstetrical patient. Whichever method is used (ventilation through a facial mask or laryngeal mask, transtracheal oxygenation), the anesthetist must never forget that the first priority is always the safety of the mother.

[Flecainide and paroxysmal supraventricular tachycardia in the operating room]. / Flecaïnide et tachycardie supraventriculaire paroxystique en salle d'opération.

The case is reported of a 52-year-old woman who developed paroxysmal supraventricular tachycardia prior to induction of general anesthesia. This arrhythmia, resistant to vagal stimulation and verapamil, was finally ended by the administration of flecainide in the operating room.

[Principles of the measurement of energy expenditure]. / Principes de la mesure de la dépense énergétique.

Numerous methods can be used to assess energy expenditure (EE). The Fick method allows an easy calculation of EE in critically ill patients with Swan-Ganz catheters. Indirect calorimetry can be performed using either closed circuit or open circuit techniques. The latter is accurate when the patient is breathing air or low-FiO2 gaz mixture, but inaccurate at high FiO2. The accuracy of instruments, the presence of a leak-free system and the mathematical manipulations are critical points. Calorimetric studies performed in patients receiving high FiO2 must be interpreted with caution.

[Principles of the use of indirect calorimetry in intensive care]. / Principes d'utilisation de la calorimétrie indirecte en médecine intensive.

Energy expenditure measurements in critically ill patients using indirect calorimetry is complex and often very inaccurate. Analysis of the data should first question their validity. The components of energy expenditure should be carefully separated to assess the effects of illness, drugs and supportive treatments.

Effect of propofol on cerebrospinal fluid pressure and cerebral perfusion pressure in patients undergoing craniotomy.

The effects of propofol on cerebrospinal fluid pressure, mean arterial pressure, cerebral perfusion pressure and heart rate were studied during induction, tracheal intubation and skin incision in 23 patients scheduled for elective craniotomy. Premedication consisted of midazolam 0.1 mg/kg intramuscularly and metoprolol 1 mg/kg orally. Measurements were made or derived at time zero and 0.5, 1, 1.5, 2 and 3 minutes after an induction dose of propofol 1.5 mg/kg. A continuous infusion of propofol was started at time zero at a rate of 100 mg/kg/minute. Fentanyl 2 micrograms/kg was added before tracheal intubation, application of the pin head holder and skin incision. Cerebrospinal fluid pressure and mean arterial pressure decreased significantly 2 minutes after propofol alone, by 32% and 10% respectively, while a cerebral perfusion pressure above 70 mmHg was maintained. Heart rate did not change. Propofol combined with moderate dose of fentanyl, obtunded the usual cerebrospinal fluid and arterial pressure responses to intubation and other noxious stimuli. Thus propofol seems to be a suitable intravenous anaesthetic agent for induction and maintenance in neuroanaesthesia.

[Difficult intubation in obstetrics]. / Intubation difficile en obstétrique.

The obstetrical population is prone to difficult or failed intubation. Control of the airway is complicated by several factors specific to obstetric anesthesia: time of apnea is short due to a reduced functional residual capacity and pregnancy-induced hypertension and obesity are relatively frequent; anesthetist's skill can also be mentioned. The best approach to this problem lies in its prevention, using epidural analgesia as soon as possible. Furthermore, the number of difficult intubations can be considerably reduced by a thorough pre-anesthetic examination. Each anesthetist must keep an algorithm in mind, should a difficult or failed intubation in obstetrical patient occur. Whichever method is used (ventilation through a facial mask or laryngeal mask, transtracheal oxygenation), the anesthetist must never forget that the first priority is always the safety of the mother.

Glucose disposal in obese non-diabetic and diabetic type II patients. A study by indirect calorimetry and euglycemic insulin clamp.

Insulin resistance is a characteristic finding in obesity and in non insulin dependent (Type II) diabetes mellitus. However, the interaction between diabetes and obesity has been poorly characterized and the metabolic disturbances contributing to the defect in insulin-mediated glucose uptake have not been defined. To examine these questions euglycemic and hyperinsulinemic clamp studies (40 mU/m2/min) were performed in 10 control non-obese subjects, 10 non diabetic obese subjects, 8 normal weight Type II diabetics, and 12 obese Type II diabetics. During the insulin clamp study total body glucose uptake in the obese non diabetics (157 +/- 18 mg/m2.min, p less than 0.01), the normal weight diabetics (159 +/- 21, p less than 0.01) and the obese diabetics (125 +/- 11, p less than 0.001) was significantly reduced compared to the non-obese non diabetic control group (249 +/- 22 mg/m2.min). The impairment in total body glucose uptake was the result mainly of a defect in non-oxidative glucose disposal. Indeed non-oxidative glucose disposal was blunted by 50% in the obese groups (p less than 0.01), somewhat less significantly in the non-obese diabetic group (p less than 0.05) but more when obesity and diabetes mellitus were combined (p less than 0.001). Total glucose oxidation was significantly diminished (p less than 0.01) in both diabetic groups but not in the obese non diabetic group when compared to lean control. A significant inverse correlation between the fasting free fatty acids levels and total glucose uptake (r = -0.453, p less than 0.001) and total glucose oxidation (r = -0.446, p less than 0.001) during the clamp was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorto-subclavian thromboembolism: a rare complication associated with moderate ovarian hyperstimulation syndrome.

The case of an arterial aorto-subclavian thromboembolism associated with a moderate ovarian hyperstimulation syndrome (OHSS) and following ovulation induction for in-vitro fertilization in a young woman is reported. Because of the lack of response to systemic thrombolysis, a left postero-lateral thoracotomy was performed on day 8 after embryo transfer. A fibrinocruoric embolus situated at the junction of the left subclavian artery from the aorta was removed through a left subclavian arteriotomy. The distal axillary embolus was removed by a retrograde balloon catheter embolectomy. A moderate OHSS was observed. The ovarian stimulation and OHSS-related risks of thromboembolism are discussed. We conclude that, in the absence of risk factors, counselling about possible complications resulting from stimulation must be emphasized.

Intrathecal clonidine and fentanyl with hyperbaric bupivacaine improves analgesia during cesarean section.

UNLABELLED: Seventy-eight pregnant women at term, scheduled for elective cesarean section, were enrolled in this multicenter trial to compare the analgesic efficacy and side effect profile of a spinal block with hyperbaric bupivacaine alone (Group B) or combined with 75 microg of clonidine (Group BC) or with clonidine 75 microg and fentanyl 12.5 microg (Group BCF). Intraoperatively, clonidine increased the spread of the sensory block and decreased pain (pain scores 23+/-7 mm vs 17+/-6 and 2+/-1 mm for Group B versus Groups BC and BCF; P < 0.05) and analgesic supplementation. This improved analgesia was best with the clonidine-fentanyl combination (Group BC versus Group BCF; P < 0.05). Postoperative analgesia was prolonged only in Group BCF (215+/-79 min vs 137+/-35 and 183+/-80 min for Group BCF versus Groups B and BC; P < 0.05). Blood pressure and heart rate changes were not significantly different among groups, whereas sedation and pruritus were significantly more frequent in Group BCF. Nausea and vomiting were decreased in Groups BC and BCF. Apgar scores and umbilical artery blood pH were not different among groups. We conclude that adding a small dose of intrathecal clonidine to bupivacaine increases the quality of intraoperative analgesia and decreases pain during cesarean section. Combining clonidine with fentanyl further improved analgesia. IMPLICATIONS: In this study, we demonstrate improved intraoperative spinal analgesia by adding 75 microg of clonidine to bupivacaine; side effects were not increased. The combination of clonidine and fentanyl further improved analgesia but moderately increased sedation and pruritus.

Hyperosmolarity does not contribute to transient radicular irritation after spinal anesthesia with hyperbaric 5% lidocaine.

BACKGROUND AND OBJECTIVES: In addition to major neurologic injury, local anesthesia toxicity may also include less severe but more common neurologic side effects. The authors recently observed symptoms suggestive of transient radicular irritation in one third of patients after spinal anesthesia with hyperbaric 5% lidocaine, whereas evidence of neurologic symptoms was lacking with hyperbaric 0.5% bupivacaine. The purpose of this prospective double-blinded study was to evaluate if the high osmolarity of hyperbaric 5% lidocaine solution might contribute to the development of transient radicular irritation. METHODS: Forty-four patients undergoing brief gynecologic procedures under spinal anesthesia were randomly allocated to receive 1.5 mL of one of three study drugs: 5% lidocaine in 7.5% dextrose (drug A), 0.5% bupivacaine in 8.25% dextrose (drug B), or 5% lidocaine in 2.7% dextrose (drug C). Drug C was prepared by the pharmacy (University Hospital, Basel, Switzerland) with an osmolarity similar to that of drug B. Drugs A and B were commercially available. Patients were evaluated on postoperative day 1 for symptoms of transient radicular irritation by an anesthesiologist who was unaware of the drug given or details of the anesthetic technique. RESULTS: Symptoms suggestive of transient radicular irritation were observed with a similar high incidence in patients receiving both lidocaine preparations, but in no patient receiving hyperbaric 0.5% bupivacaine (P < .01). CONCLUSIONS: The results suggest that transient radicular irritation did not result from the marked hyperosmolarity of the hyperbaric 5% lidocaine. However, because lidocaine and bupivacaine were not administered at equipotent dosages, the relative potential for both drugs to induce transient radicular irritation remains to be determined.