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Newer neuromuscular blocking drugs. An overview of their clinical pharmacology and therapeutic use.

Four new nondepolarising muscle relaxants, pipecuronium bromide, doxacurium chloride, mivacurium chloride and Org 9426 (rocuronium) offer alternatives to the established agents atracurium besilate and vecuronium bromide. Pipecuronium and Org 9426 are steroidal compounds, the latter being a monoquaternary agent, whereas doxacurium and mivacurium are bisquaternary benzylisoquinolinium compounds. Pipecuronium and doxacurium have a relatively slow onset and a long duration of action. Pipecuronium produces maximum block in 3 to 6 min when given in a dose of 45 to 80 micrograms/kg, and a duration of clinical relaxation of between 40 and 110 min. Doxacurium is more potent, but is the least rapid and the longest acting relaxant currently available. When administered in doses of 37 to 80 micrograms/kg, it produces maximum block within 3.5 to 10 min, with a duration of clinical relaxation of 77 to 164 min. The advantage of both pipecuronium and doxacurium is their cardiovascular stability. Both agents are primarily eliminated via the kidneys and both have now been licensed for use in the US. Mivacurium is a muscle relaxant with a short duration of action. When administered in doses of 0.1 to 0.25 mg/kg it produces maximum block in 2 to 4 min, but the duration of clinical relaxation is less than 20 min. Higher doses which could induce a faster neuromuscular block are unfortunately associated with some histamine liberation. The drug is metabolised by plasma cholinesterase. Mivacurium has also been licensed for use in the US. Org 9426 is an agent with a rapid onset but an intermediate duration of action. A dose of 0.5 to 0.6 mg/kg induces maximum block in about 1.5 min and has a duration of clinical relaxation of about 30 min. The rapid onset of effect could be useful for early intubation as an alternative to suxamethonium chloride. However, much more clinical experience is needed with this agent, particularly with regard to duration of action of larger doses and occurrence of side effects. The drug is mainly eliminated via the liver.

Aging↗

Hemodynamic changes during laparoscopic cholecystectomy monitored with transesophageal echocardiography.

Although pneumoperitoneum has been well tolerated in a predominantly healthy population, there is concern that an increased intraperitoneal pressure may be poorly tolerated in patients with marginal cardiopulmonary function. The purpose of this study was to demonstrate noninvasively the hemodynamic effects of carbon dioxide pneumoperitoneum utilizing biplane transesophageal echocardiography. Fourteen otherwise-healthy patients undergoing nonemergent laparoscopic cholecystectomy were studied using bi-plane transesophageal echocardiography under a standardized anesthetic protocol utilizing isoflurane, fentanyl, and vecuronium bromide. End-tidal CO2, oxygen saturation, cardiac rhythm, temperature, and blood pressure were monitored noninvasively. Minute ventilatory volume was adjusted as needed to keep end-tidal CO2 less than 38 mmHg. Data were recorded at baseline, following abdominal insufflation to 15 mmHg with CO2, with head-up tilt of 20 degrees, following exsufflation, and with the patient level. Significance was determined using a paired Student t-test. Insufflation to 15 mmHg decreased cardiac index (C.I.) by 3% (3.34 to 3.23 l/min/m2) while both heart rate (HR) and mean arterial pressure (MAP) increased (by 7% and 16%), respectively, and stroke volume index decreased by 10% (from 51.6 to 46.6 ml/beat/m2). Head-up tilt of 20 degrees further decreased CI to 2.98 l/min/m2 (-11%) and SVI to 40.3 ml/beat/m2 (-22%) while HR increased by a total of 14% and MAP by 19%. As laparoscopic techniques are applied to a broader population, the impact of small but significant decrements in cardiac function become increasingly important. This study demonstrates that the combination of CO2 pneumoperitoneum and the reverse Trendelenburg position does adversely effect cardiac output.

Adolescent↗

Total intravenous anaesthesia with propofol, alfentanil, and oxygen-air: three different dosage schemes.

Three different dosage schemes of propofol infusions combined with a fixed-rate alfentanil infusion were investigated in total intravenous anaesthesia. In 30 premedicated patients, divided at random into three groups, anaesthesia was induced with propofol 2 mg.kg-1 immediately followed by an alfentanil infusion 10 micrograms.kg-1.min-1 as a loading dose which was decreased after ten minutes to a maintenance dose of 1 microgram.kg-1.min-1. Vecuronium bromide 0.1 mg.kg-1 was used as the muscle relaxant. After induction of anaesthesia a propofol infusion 2 mg.kg-1.hr-1 was started in group A, 3 mg.kg-1.hr-1 in group B and 4 mg.kg-1 hr-1 in group C. At signs of light anaesthesia supplementary bolus doses of 20 mg propofol and 1 mg alfentanil were given. The patients' lungs were ventilated with air-oxygen (FIO2 0.35). The mean systolic and diastolic blood pressures showed no statistical significant differences between the three groups. A significant (P less than 0.01) decrease of the mean systolic and diastolic blood pressures was present after induction of anaesthesia and tracheal intubation. Recovery was uneventful in all but one patient, who had ventilatory depression that responded to naloxone (0.2 mg IV). Awareness did not occur in any patient. The only difference between the three groups was the higher number of supplementary bolus doses of propofol and alfentanil needed in group A (P less than 0.01). In total intravenous anaesthesia propofol 3 and 4 mg.kg-1.hr-1 as a maintenance dose combined with a two-step fixed-rate alfentanil infusion provided smooth anaesthesia and uneventful rapid recovery.

Adolescent↗

Intramuscular tramadol increases gastric pH during anesthesia.

PURPOSE: Tramadol, [(1RS, 2RS)-2-dimethylamino) methyl-1-(3-methoxyphenyl)-cyclohexanol hydrochloride], is an analgesic in clinical use. It has been reported that tramadol inhibits muscarinic type 3 receptor function, which primarily mediates smooth muscle contraction and glandular secretion. We investigated the effects of tramadol on the pH of gastric juices during anesthesia to determine whether tramadol inhibits secretion from the gastric glands. METHODS: ASA physical status I or II adult patients (n = 30) presenting for major elective orthopedic surgery of the upper extremities or mastectomy were enrolled. Patients were randomly assigned to receive treatment with tramadol (n = 10), famotidine (n = 10), or saline (n = 10). General anesthesia was then induced using propofol, vecuronium bromide, and fentanyl. After inducing anesthesia, the gastric pH was measured using pH test paper and, then, 100 mg tramadol, 20 mg famotidine, or saline were injected into the deltoid muscle. Three hours after starting the operation, gastric juice was again aspirated and its gastric pH measured. RESULTS: There were no differences in the pH before anesthesia between the three groups. By contrast, gastric pH was increased in the tramadol group by the same amount as it was in the famotidine group three hours after administering the drugs. Gastric pH of the saline, famotidine, and tramadol groups was 2.6 +/- 2.5, 6.3 +/- 2.0, and 6.4 +/- 0.8, respectively. CONCLUSION: These results suggest that tramadol inhibits the secretion of gastric acid.

Adult↗

Benign hyperthermia following prolonged TIVA with propofol.

PURPOSE: Propofol is widely used for general anesthesia because of its rapid onset and recovery. We had four cases that had higher body temperatures toward the end of anesthesia. The etiology of the hyperthermia is discussed. CLINICAL FEATURES: Four patients (three male, one female, 22-26 yr of age, weighing 53-57 kg) with facial deformities were anesthetized with propofol infusion (3-10 mg x kg(-1) x hr(-1)) and fentanyl (400-1,300 microg) without nitrous oxide, immobilized with vecuronium bromide (18-37 mg) or pancuronium bromide (31 mg). In order to reduce blood loss and improve the surgical view, tri-nitro-glycerin (TNG) was used in all cases. Osteotomy of maxilla and mandible or sagittal split ramus osteotomy of mandible was successfully performed. Although their body temperatures were normal preoperatively and stable during the operation, toward the end of anesthesia (one hour), they increased to over 38 degrees C. The room temperature was decreased and the water blanket on the operating table was also decreased. In addition, cool crystalloid solution was infused. Body temperature returned to normal in the ward and no complications due to the high temperature were seen postoperatively. It is thought that lighter anesthesia was masked by continuous infusion of propofol and TNG-induced hypotension and that benign hyperthermia occurred toward the end of anesthesia. CONCLUSION: Propofol reduces blood pressure, which suggests deep anesthesia. However, care must be taken to maintain the optimum depth of anesthesia during propofol anesthesia, especially when deliberate hypotensive anesthesia is induced.

Adult↗

[No inhibition of intestinal motility following ketamine-midazolam anesthesia. A comparison of anesthesia with enflurane and fentanyl/midazolam].

Postoperative intestinal atonia is a complication which is likely to occur in patients predisposed for constipation and in patients after intra-abdominal operations. The postoperative delay of bowel movement, however, is often also related to the type of anaesthesia being used. In order to evaluate the magnitude of an anaesthetic-induced postoperative delay of bowel movement, two types of intravenous-based anaesthesia using fentanyl/midazolam (1 mg/25 mg; dosage 0.1 ml/kg/h), and ketamine/midazolam (250 mg/25 mg; dosage 0.1 ml/kg/h) respectively were compared with a volatile anaesthetic technique (enflurane; mean concentration 1.5 vol%). METHODS. In three groups of patients (each n = 15) undergoing elective surgery of the lower extremities, induction of anaesthesia was accomplished with methohexital (1-1.5 mg/kg) to facilitate intubation. For the maintenance of muscle relaxation vecuronium bromide was used. All patients were given droperidol to prevent postoperative emesis, and they were artificially ventilated with N2O/O2 (60:40) to normal end-expiratory CO2 concentrations. No anticholinergic agents were used at the end of operation since they are known to interfere with bowel motility. In order to determine gastro-intestinal motility, the H2 exhalation test was used. For this purpose 40 g lactulose in 100 ml of water was given to all patients via a gastral tube shortly before extubation. Lactulose is broken down by bacteria once it enters the colon, and H2 is released, taken up by the vascular system and exhaled. Postoperatively, patients were asked to exhale into a 20-ml syringe every 10 min. The content was analysed for hydrogen (ppm), using an electrochemical sensor (GMI exhaled hydrogen monitor). From the time of lactulose instillation to a threefold increase in end-expiratory hydrogen concentration (compared to the preoperative value), gastro-coecal transit time was computed. RESULTS. All three groups of patients were comparable in age, height and body weight. Also, the duration of operation was comparable in all three groups. Mean gastro-coecal transit time was 204 (+/- 19.6, SD) min following enflurane, 302 (+/- 32.8 SD) min following fentanyl/-midazolam and 210 (+/- 28.8 SD) min following ketamine/midazolam anaesthesia. The gastro-intestinal inhibition after the opioid-based anaesthetic technique was significantly prolonged (p < 0.001, Kruskal-Wallis test). There was no significance between patients after ketamine-based anaesthesia and those who had the volatile anaesthetic. DISCUSSION AND CONCLUSION. When using intravenous anaesthesia with an opioid, gastro-intestinal inhibition, especially in patients prone to have constipation, is likely to develop postoperatively. In classical neuroleptanaesthesia and in analgosedation in the ICU, the simultaneous use of the butyrophenone droperidol seems to counteract the inhibition of opioid-related gastrointestinal motility. In cases of opioid-related gastrointestinal atonia a gastrokinetic compound may be necessary to overcome this effect on intestinal motility.

Adult↗

[The effect of convection warming during abdominal surgery on the early postoperative heat balance].

UNLABELLED: Hypothermia (core temperature < 36 degrees C) is common after longer-lasting surgical procedures. Heat loss mainly occurs during anaesthesia and surgery and leads to increased risk, especially in the early recovery period of elderly patients. In the present study we investigated the effects of intraoperative forced-air warming, administered via an upper-body blanket ("Warm Touch", Mallinckrodt, USA), with the specific aims of: (1) drawing up heat balances; and (2) analysing postoperative thermoregulation, oxygen consumption (VO2) and cardiovascular reactions of mechanically ventilated patients. The general aim of our study was to compare intraoperative forced-air-warming and conventional patient-insulation with cotton blankets. METHODS: Twenty four ASA II and III patients scheduled for elective colon surgery were randomly assigned to a control group (n = 12, no warming therapy, upper body covered with a cotton hospital blanket) or a convective warming group (n = 12). Anaesthesia was administered with etomidate (0.2 mg/kg), fentanyl (approximately 10 micrograms/kg) and vecuronium bromide (0.1 mg/kg). During surgery the lungs were mechanically ventilated with 70% nitrous oxide in oxygen and enflurane (end-tidal-concentration max. 0.7%) using a semiclosed circuit with a fresh gas flow of 3 l/min. A hygrophobe heat and moisture exchanger ("Sterivent," Darex Corp., Italy) was used. At the end of surgery patients were transferred to the ICU, covered with a hospital cotton-quilt and normo-ventilated using a Bennett 7200 a. Patients were sedated/kept free of pain by administering titrated doses of midazolam and/or piritramide. Postoperative oxygen consumption (VO2) was recorded continuously with a Deltatrac Metabolic Monitor (Datex Corp., Finland). Pre-, intra- and postoperative measurements included heart rate, invasive blood pressure, core-temperature (before and after operation: urinary bladder-temperature, during surgery: oesophageal temperature) and mean-skin-temperature (according to Ramanathan) up to 180 min from the end of surgery. Shivering, pharmacological interventions (e.g. pethidine) and time of extubation were noted. Data are presented as median, minima and maxima. The results were analysed using the Mann-Whitney U test or Chi-Square test (shivering). Statistical significance was assumed when P < 0.05. RESULTS: Both groups were comparable for gender, body weight, height, age, duration of their operations and amount of intraoperative fluids, narcotics and muscle relaxants. Room temperatures in the control group were significantly higher than in the forced air group (24 vs 22 degrees C). Initial setting of the forced-air blower was "high" (42-46 degrees high air flow). When the oesophageal-temperature reached 36.5 degrees C, the blower temperature was reduced to 36-40 degrees C. Reduction was necessary approximately 60 min from start in the operation. At the end of surgery/administration to the ICU core-temperatures of both groups differed significantly (35.2/ 35.4 degrees C vs 36.3/36.2 degrees C). Mean-skin temperatures were higher, too, but no statistical analysis was carried out for the intraoperative period, because warm air influenced skin thermometers located on the upper body. At admission to the ICU patients in the control group had a heat loss of 4.4 kJ/kg; those in the convective warming group had a heat-gain of 0.8 kJ/kg. Further measurements of postoperative core temperatures did not differ significantly, but the skin-temperatures of patients who received forced-air warming in the theatre remained higher (P < 0.05) until 120 min from the end of surgery. Shivering was more frequent and lasted longer in the control group (8 patients, 20 min vs 4 patients, 9 min; P < 0.05). Patients in the control group needed more drugs to stop increased cardiovascular reactions (hypertension, tachycardia) or shivering.(ABSTRACT TRUNCATED)

Adult↗

Thoracic versus lumbar epidural fentanyl for postthoracotomy pain.

Thirty patients were prospectively randomized to receive either thoracic or lumbar epidural fentanyl infusion for postthoracotomy pain. Epidural catheters were inserted, and placement was confirmed with local anesthetic testing before operation. General anesthesia consisted of nitrous oxide, oxygen, isoflurane, intravenous fentanyl citrate (5 micrograms/kg), and vecuronium bromide. Pain was measured by a visual analogue scale (0 = no pain to 10 = worst pain ever). Postoperatively, patients received epidural fentanyl in titrated doses every 15 minutes until the visual analogue scale score was less than 4 or until a maximum fentanyl dose of 150 micrograms by bolus and an infusion rate of 150 micrograms/h was reached. The visual analogue scale score of patients who received thoracic infusion decreased from 8.8 +/- 0.5 to 5.5 +/- 0.7 (p < or = 0.05) by 15 minutes and to 3.5 +/- 0.4 (p < or = 0.05) by 45 minutes. The corresponding values in the lumbar group were 8.8 +/- 0.6 to 7.8 +/- 0.7 at 15 minutes and 5.3 +/- 0.9 at 45 minutes (p < or = 0.05). The infusion rate needed to maintain a visual analogue scale score of less than 4 was lower in the thoracic group (1.55 +/- 0.13 micrograms.kg-1 x h-1) than in the lumbar group (2.06 +/- 0.19 microgram.kg-1 x h-1) during the first 4 hours after operation (p < or = 0.05). The epidural fentanyl infusion rates could be reduced at 4, 24, and 48 hours after operation without compromising pain relief. Four patients in the lumbar group required naloxone hydrochloride intravenously.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia, Epidural↗

Histological investigations of muscle atrophy and end plates in two critically ill patients with generalized weakness.

We describe pathological alterations at the light microscopical and ultrastructural level of motor end plates and muscle fibres in 2 critically ill patients with generalized muscular atrophy and weakness. Axonal degeneration of intramuscular nerve fibres was not conspicuous. The sural nerve in one patient showed only minor abnormalities. There was a marked atrophy of type 1 and especially type 2 muscle fibres. Nodal and ultraterminal nerve sprouts were seen in both biopsies. Motor end plates showed features of regeneration. They were enlarged in one patient. This patient was treated for a prolonged period with vecuronium bromide. Pharmacological denervation may explain the presence of fibrillation potentials, and, partially, of the histological abnormalities. Another factor which must be considered is inhibition of neuromuscular transmission by antibiotics. In addition to disuse atrophy and a minor degree of axonal neuropathy, the production of muscle proteolytic factors may be involved in the rapidly occurring massive loss of muscle fibre size in critically ill patients.

Atrophy↗

Sympathetic nervous activity to brown adipose tissue increases in cold-tolerant mice.

Brown adipose tissue (BAT) is thought to be responsible for increased heat production in cold-acclimated rodents. We measured sympathetic nerve activity (SNA) in interscapular BAT (IBAT) during cold stimulation in cold-acclimated C57BL/6J mice (ACCLI). Cold acclimation was achieved (cold tolerance was increased) by repeated exposure to cold stress every other week for 3 weeks. We compared SNA in these animals with SNA in mice that had no previous cold stress experience (naive). During the test, mice were anesthetized by urethane and isoflurane and were paralyzed with vecuronium bromide. Sympathetic nerve activity was recorded directly from one of the fine nerves to IBAT. The animal's body caudal to the pelvic area was covered with a plastic bag containing a slurry of ice water to decrease colonic temperature 7 degrees C below control level, which took approximately 20 min. Interscapular BAT-SNA increased during cold stress in both groups, but ACCLI mice had higher IBAT-SNA during cold stress than naive mice. These findings confirmed the hypothesis that during the acute cold exposure, cold-acclimated mice have greater sympathetic outflow to BAT adipocytes.

Acclimatization↗

Sympathetic outflow to interscapular brown adipose tissue in cold acclimated mice.

C57BL/6J male mice were subjected to a cold acclimation procedure which consisted of three consecutive cold stress tests: 3-h partial restraint at 6 degrees C at 2-wk intervals. During the week following the last cold stress test, each animal previously subjected to the cold acclimation procedure, and an additional group of naive mice (animals that never had been exposed to an environment below room temperature) were anesthetized with urethan, paralyzed with vecuronium bromide, artificially ventilated, and subjected to cold stimulation for approximately 16 min. Electrical impulse activity from one of the fine sympathetic nerves entering the interscapular brown adipose tissue was recorded before and during cold stimulation, until body temperature dropped 8 degrees C below control level. Sympathetic outflow increased significantly during cold stimulation in all mice. Animals that did not achieve cold acclimation in three repeated cold stress tests (they demonstrated less cold tolerance in the last test) had lower sympathetic nervous outflow to brown adipose tissue at room temperature and during cold stimulation than mice that had achieved cold acclimation. In fact, sympathetic nervous outflow to brown adipose tissue in mice that had failed to show cold acclimation was similar to that of naive mice. These findings indicate that the sympathetic nervous system plays a primary role in cold acclimation.

Acclimatization↗

The effect of laryngeal mask cuff pressure on postoperative sore throat incidence.

STUDY OBJECTIVE: To study the effect of laryngeal mask airway (LMA) cuff pressure on the incidence of postoperative sore throat. DESIGN: Prospective, randomized, observational study. SETTING: Operating room of a university hospital. PATIENTS: 200 consecutive adult patients requiring anesthesia for gynecologic procedures. INTERVENTIONS: Anesthesia was induced with thiopental 3-5 mg/kg, fentanyl 2 micrograms/kg, vecuronium bromide 0.05mg/kg, and enflurane 0.8% to 2% and maintained with nitrous oxide and oxygen (65%/35%) and enflurane. MEASUREMENTS AND MAIN RESULTS: In Group 1, cuff pressure measurement was continuously performed until the end of the operation. In Group 2, 5 minutes after induction of anesthesia and 2 minutes after insertion of the LMA, cuff pressure was also continuously observed and reduced to the minimal pressure required for airtightness. In the recovery room, after the operation, patients were questioned for postoperative sore throat 4, 8, and 24 hours after the operation following a scoring protocol (score 0 = no complaints, score 1 = minimal sore throat, score 2 = moderate sore throat, score 3 = severe sore throat: "never a LMA again". Continuous monitoring of cuff pressure revealed a steady increase of pressure (during the first 60 minutes increases of 43 cm H2O) in Group 1. In Group 2, after release of air, cuff pressures were significantly lower through the entire operation when compared with Group 1. In Group 1, 8 patients claimed to have a sore throat (Score 1, n = 4; Score 2, n = 3; Score 3, n = 1). In Group 2, no patient complained of sore throat. CONCLUSIONS: A significant increase in cuff pressure is seen during the first 60 minutes. Three minutes after insertion of the laryngeal mask, cuff pressure can significantly be reduced without any major gas leakage. Postoperative sore throat can be reduced when cuff pressure is continuously monitored and kept on low-pressure values.

Adult↗

Effect of aerosolized milrinone during drug-induced pulmonary hypertension in lambs.

We tested whether aerosolized milrinone in lambs selectively reduces drug-induced acute pulmonary hypertension without reducing the mean systemic blood pressure (MSBP). Seven, 2-3-week-old lambs were anesthetized (50 mg/kg ketamine), paralyzed (0.1 mg/kg vecuronium bromide) and mechanically ventilated. A femoral artery, pulmonary artery, and jugular vein were catheterized for continuous monitoring of MSBP, mean pulmonary artery pressure, periodic gas-exchange analyses, and determination of cardiac output by thermodilution technique. An Airlife Misty nebulizer was used in a dry state to establish a stable baseline of an inspired fraction of oxygen (FiO(2)) at 0.21. Acute pulmonary hypertension with hypoxemia was then induced by increasing the mean pulmonary artery pressure up to 30-35% of the MSBP using 2-6 microg/kg/min of Thromboxane A(2) mimetic (U-46619), intravenously. The lambs were then subjected to 15 min of saline nebulization without milrinone followed by 30 min saline nebulization with a relatively high concentration of milrinone (10 mg/ml, total dose of 40 mg). Aerosolized milrinone had no effect on systemic or pulmonary artery pressure during combined acute pulmonary hypertension and hypoxemia. We speculate that our nebulization procedures failed to deliver sufficient amount of milrinone for producing a detectable hemodynamic effect.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

The clinical spectrum of critical illness polyneuropathy.

OBJECTIVE: To describe the entity of critical illness polyneuropathy and review our experience with six cases. DESIGN: We present case reports of six patients with polyneuropathy associated with critical illness, who received medical care at the Mayo Clinic between 1992 and 1994, and discuss similar cases from the literature. RESULTS: Critical illness may damage peripheral nerves. In previous studies, sepsis and multiorgan failure have been found to trigger a peripheral neuropathy. Of our six patients with critical illness polyneuropathy, all had a preceding severe bacterial infection or septic shock. In one patient who had long-term administration of vecuronium bromide and had received massive intravenous doses of corticosteroids, sural nerve and quadriceps muscle biopsy specimens were available; they revealed axonal neuropathy and notable myopathic changes, respectively. The outcome was good in patients who survived the critical illness. CONCLUSION: Polyneuropathy in critically ill patients may be a cause of severe generalized limb weakness and occurs in the setting of a sepsis syndrome. The long-term outcome is good in patients who recover from the underlying critical illness. Compression neuropathies may be a cause of permanent sequelae.

Acute Disease↗

Cold acclimation-associated changes in brown adipose tissue do not necessarily indicate an increase of nonshivering thermogenesis in C57BL/6J mice.

We have reported previously that a cold acclimation procedure (3-hr partial restraint at 6 degrees C, repeated 3 times at 2-week intervals) usually improves the cold tolerance of adult C57BL/6J mice. Those mice that did not improve their cold tolerance had lower cold-induced sympathetic nervous outflow to the interscapular brown adipose tissue (IBAT), suggesting a failure in the mechanisms of nonshivering thermogenesis. To understand the origin of this failure, this study was intended to measure nonshivering thermogenesis in mice that did not improve their cold tolerance after the cold acclimation procedure. After being subjected 3 times to a partial restraint at 6 degrees C, mice were anesthetized with urethane, immobilized with vecuronium bromide, and placed on artificial ventilation. The VO2 and VCO2 in expired air were measured and metabolic heat production (MHP) was calculated while body temperature was artificially lowered to 7.5 degrees C below control level. In a separate group of mice, the total amount and concentration of mitochondrial uncoupling protein, thermogenin (UCP), in IBAT was measured immediately after completion of the cold-acclimation procedure. The concentration and the amount of UCP in the mitochondria of IBAT was significantly higher in all mice that had been presented to the cold acclimation procedure, regardless of its outcome, than in mice that had never been exposed to an environment below room temperature (NAIVE). MHP increased significantly during body cooling in all mice. However, MHP before and during cold stimulation in mice that did not improve their cold tolerance as a result of the cold-acclimation procedure was significantly lower than the MHP of animals in which cold tolerance was improved, and was not different from MHP of the NAIVE group. Therefore, in mice in which cold tolerance did not improve after repeated cold exposure, the anatomical and biochemical changes in brown adipose tissue typical of cold acclimation were not associated with a cold-induced increase in MHP. We infer that the expression of UCP in brown adipose tissue is a necessary, but not sufficient, attribute of cold acclimation. Cold acclimation, measured as increased cold tolerance, occurs only if synthesis of UCP in BAT is associated with an increased cold-induced response of the sympathetic nervous system.

Acclimatization↗

[Tracheal intubation in patients with cervical spine injuries using a fiber optic laryngoscope].

Eleven patients, with a cervical spine injury and scheduled for elective cervical spine fusion at least 48 h after their initial trauma, were intubated using a new fiberoptic laryngoscope (Bullard). This technique uses either a semi-rigid guide independent of the laryngoscope blade, or a rigid one attached to the blade. The cervical spine was immobilized with either a collar or a halo. General anaesthesia was carried out with thiopentone, fentanyl and vecuronium bromide. Orotracheal intubation was successful at the first attempts in 10 out of the 11 patients. No mobilization of the cervical spine occurred. In the first six patients, the semi-rigid guide was used, and the rigid one in the remaining five. The anaesthetist who carried out the intubations was always the same. Using the rigid guide was easier than the semi-rigid one. This is confirmed by the time required, 44 +/- 22 sec for the rigid guide, and 97 +/- 92 sec for the semi-rigid one. In the patient in whom this technique failed at the first attempt, endotracheal intubation was carried out by the nasal route and controlled by the fiberoptic laryngoscope. This technique enables a rapid and easy orotracheal intubation in trauma patients with an immobilized cervical spine, but careful training is necessary.

Adolescent↗

[Determination of the dose-response curve for atracurium dibesylate in the anesthetized adult].

The mechanical response of the adductor pollicis to a 0.15 Hz stimulation of the ulnar nerve was studied in 35 unpremedicated adult patients (mean age 38 yr) under general anaesthesia using thiopentone, fentanyl and a N2O/O2 mixture under mechanical ventilation. PaCO2, pH, K, Ca, Mg plasma levels and temperature were in the normal range. Each patient received a single bolus of atracurium dibesylate: 0.10 mg . kg-1 (n = 11), 0.15 mg . kg-1 (n = 10), 0.20 mg . kg-1 (n = 11) or 0.30 mg . kg-1 (n = 4). The dose-response curve was constructed using the log-probit method for 0.10, 0.15, 0.20 mg . kg-1 doses, giving neuromuscular blocks greater than 0% and less than 0.20 mg . kg-1. The 0.20 mg . kg-1 dose had an onset time of 6.1 +/- 0.6 min, duration 0-90% of 34.3 +/- 3.2 min and a recovery index 25-75% of 10.9 +/- 1.0 min. The 0.3 mg . kg-1 dose resulted in onset time of 4.7 +/- 1.3 min, duration of 39.9 +/- 3.7 min and a recovery index of 10.7 +/- 1.8 min. Thus atracurium dibesylate seemed to be an agent of intermediate potency. Onset time was approximately the same as that for other non-depolarizing neuromuscular blocking drugs, but duration of action and recovery index were quite shorter, except for vecuronium bromide.

Adult↗

Experimental critical care in ventilated rats: effect of hypercapnia on arterial oxygen-carrying capacity.

PURPOSE: We have previously demonstrated an increased arterial O2-carrying capacity in normal ventilated dogs subjected to both acute and prolonged exogenous hypercapnia. In the present study, we tested if arterial hypercapnia, during controlled ventilation, can increase O2-carrying capacity also in rats. MATERIALS AND METHODS: Twenty young male Sprague Dawley rats were anesthetized (60 mg/kg pentobarbital), tracheostomized, intubated, and one femoral vein and artery were cannulated. Anesthesia and paralysis were maintained using 15 mg/kg/h pentobarbital intravenously, and 2 mg/kg/h vecuronium bromide. The fluid balance (5 mL/kg/h saline), normothermia, and minute volume were maintained. The mean arterial blood pressure and heart rate were continuously monitored. Experiments included the following: (1) a control group, ventilated with normoxic air for 150 minutes (n = 5); (2) mild hypercapnia, a group of eight rats ventilated with normoxic air for 30 minutes and then ventilated with a mixture of normoxic air at 60 mm Hg CO2 (8 kPa) for 1 hour; and (3) severe hypercapnia, a group of seven rats were treated exactly as in group II, except a 90 mm Hg (12 kPa) CO2 during hypercapnia. Gas-exchange profile, arterial hemoglobin (Hb) concentration, arterial Hb-oxygen saturation (Hb-O2), and arterial O2 content were periodically determined during normocapnia and 1 hour of hypercapnia. RESULTS: Exposures to mild and severe hypercapnia, in rats with maintained ventilation, significantly reduced the arterial O2 content by 20% and 33%, respectively, without significant changes in the arterial Hb concentration (-2%). Severe hypercapnia generated a significant reduction of -14% in the PaO2, but not in PaO2/ FiO2 ratio. CONCLUSION: Rats subjected to controlled ventilation and permissive hypercapnia, unlike dogs and perhaps humans, show no augmentation of Hb concentration. Hypercapnia in rats also provokes much stronger Bohr effect than in dogs. Hypercapnia-induced Bohr effect in rats is accompanied with extreme desaturations of Hb-O2, and substantial reduction in the O2-carrying capacity. We speculate that the strong hypercapnia-induced Bohr effect in rats may prevent hypoxia at the tissue level. However, to maintain a stable oxygen-carrying capacity in rats used for pulmonary critical care studies with hypercapnia, we suggest to use hyperoxia, with or without a mild hypothermia.

Analysis of Variance↗