Prevention of Lidocaine Aerosol-induced Bronchoconstriction with Intravenous Lidocaine

Background: Lidocaine applied topically provokes bronchoconstriction in persons with hyperreactive airway disease. The authors questioned whether intravenous lidocaine would prevent lidocaine-aerosol induced bronchoconstriction. They compared the effects of lidocaine administered intravenously and by the aerosol route on baseline airway tone, and on the prevention of histamine-induced bronchoconstriction in five Basenji-Greyhound dogs.

Methods: Dogs were pretreated with either intravenous or aerosol lidocaine followed by histamine aerosol challenge. On separate days, dogs were pretreated with intravenous lidocaine, followed by aerosol lidocaine administration at similar doses. Airway caliber was assessed using high-resolution computed tomography. Data were analyzed by two-way analysis of variance. Serum lidocaine concentrations were obtained.

Results: Histamine alone decreased the airway area by 32 +/- 3%. Lidocaine administered intravenously or by the aerosol route significantly inhibited histamine-induced bronchoconstriction. There was no significant difference between the two routes in preventing histamine-induced bronchoconstriction. At the dose that inhibited histamine-induced bronchoconstriction, lidocaine administered by the aerosol route decreased baseline airway area by 27 +/- 3% (P <0.01), whereas intravenous lidocaine had no effect. Intravenous lidocaine prevented lidocaine aerosol-induced bronchoconstriction, and the combination of intravenous and aerosol lidocaine significantly dilated the airways by 20 +/- 5% (P < 0.01 compared with control).     

Neuromuscular Blocking Agents' Differential Bronchoconstrictive Potential in Guinea Pig Airways

Background: Neuromuscular blocking agents are designed to antagonize nicotinic cholinergic receptors on skeletal muscle but also antagonize muscarinic receptors. Several muscle relaxants have the potential to promote bronchoconstriction due to unintended effects exemplified by histamine release of atracurium or mivacurium and detrimental interactions with muscarinic receptors by rapacuronium. Although interactions of muscle relaxants with muscarinic receptors have been extensively characterized in vitro, limited information is available on their potential interactions with airway tone in vivo.

Methods: Changes in pulmonary inflation pressures and heart rates induced by vagal nerve stimulation and intravenous acetylcholine were measured in the absence and presence of increasing doses of gallamine, pancuronium, mivacurium, vecuronium, cisatracurium, rocuronium, or rapacuronium in guinea pigs. Mivacurium's and rapacuronium's potential of inducing bronchoconstriction by histamine release was also evaluated.

Results: Rapacuronium potentiated both vagal nerve-stimulated and intravenous acetylcholine-induced increases in airway pressures, which were totally blocked by atropine but not pyrilamine. Vecuronium, rocuronium, mivacurium, and cisatracurium were devoid of significant airway effects. Mivacurium, at high doses, increased pulmonary inflation pressures, which were attenuated by pyrilamine.     

Evidence for opioid modulation and generation of prostaglandins in sulphur dioxide (SO)2-induced bronchoconstriction.

BACKGROUND: Inhalation of sulphur dioxide (SO2) provokes bronchoconstriction in asthmatic subjects. Cholinergic mechanisms contribute, but other mechanisms remain undefined. The effect of morphine, an opioid agonist, on the cholinergic component of SO2-induced bronchoconstriction was investigated, and the effect of indomethacin, a cyclooxygenase inhibitor, on SO2-induced bronchoconstriction and tachyphylaxis was studied. METHODS: In the first study 16 asthmatic subjects inhaled either ipratropium bromide or placebo 60 minutes before an SO2 challenge on days 1 and 2. On day 3 an SO2 challenge was performed immediately after intravenous morphine. In the second study 15 asthmatic subjects took either placebo or indomethacin for three days before each study day when two SO2 challenges were performed 30 minutes apart. The response was measured as the cumulative dose causing a 35% fall in specific airways conductance (sGaw; PDsGaw35). RESULTS: Ipratropium bromide significantly inhibited SO2 responsiveness, reducing PDsGaw35 by 0.89 (95% CI 0.46 to 1.31) doubling doses. This effect persisted after correction for bronchodilatation induced by ipratropium bromide. The effect of ipratropium bromide and morphine on SO2 responsiveness also correlated (r2 = 0.71). In the second study SO2 tachyphylaxis developed with PDsGaw35 on repeated testing, being reduced by 0.62 (95% CI 0.17 to 1.07) doubling doses. Indomethacin attenuated baseline SO2 responsiveness, increasing PDsGaw35 by 0.5 (95% CI 0.06 to 0.93) doubling doses. CONCLUSIONS: These results suggest that opioids modulate the cholinergic component of SO2 responsiveness and that cyclooxygenase products contribute to the immediate response to SO2.     

Pancuronium, gallamine, and d-tubocurarine compared: is speed of onset inversely related to drug potency?

The relative potency and speed of onset of action of pancuronium, gallamine, and d-tubocurarine was studied in 55 adult female patients receiving nitrous oxide/oxygen-narcotic anesthesia. The integrated electromyogram of the adductor pollicis muscle was monitored using a cumulative dose-response technique; train-of-four stimuli were administered at 0.05 Hz. The measured ED95 values for pancuronium and gallamine were 0.069 and 2.38 mg/kg, respectively. In three separate groups, pancuronium 0.07 mg/kg, gallamine 2.4 mg/kg, or d-tubocurarine 0.45 mg/kg were given as a single bolus and the speed of onset and time to maximum effect determined. Peak twitch depression was essentially identical in all groups (92.7 +/- 1.4 [SE] vs. 93.3 +/- 1.1 vs. 93.7 +/- 1.1%, respectively). The rate of onset of neuromuscular blockade in these three groups was, however, quite different. After administration of pancuronium (n = 10) the times to 5%, 20%, 50%, and 80% twitch depression were 68 +/- 5, 97 +/- 6, 141 +/- 8, and 222 +/- 18 s. The comparable times following gallamine (n = 10) were 29 +/- 2, 42 +/- 3, 66 +/- 5, and 136 +/- 14 s; d-tubocurarine (n = 10) was intermediate in speed with onset times of 40 +/- 4, 63 +/- 6, 99 +/- 11, and 178 +/- 25 s. It appears that the onset times of different nondepolarizing blocking agents (even when given in equipotent doses) may vary by clinically appreciable amounts. The results of this study support the hypothesis that nondepolarizing neuromuscular blocking agents of low potency may have a more rapid onset of action than that seen with agents of high potency.     

Effects of the α2-Adrenoceptor Agonist Dexmedetomidine on Bronchoconstriction in Dogs

Background: Tracheal intubation can elicit reflex bronchoconstriction in patients with asthma or chronic obstructive pulmonary disease, complicating mechanical ventilation and weaning from mechanical support. In vitro studies of human and animal bronchial tissue indicate that [alpha]2-adrenoceptor stimulation can lead to smooth muscle relaxation and prevention of bronchoconstriction. Dexmedetomidine is a selective [alpha]2-adrenoceptor agonist approved for sedation in the intensive care unit. Whether dexmedetomidine can affect reflex bronchoconstriction is unknown.

Methods: After the approval of the institutional animal care and use committee, five mongrel dogs were anesthetized with thiopental, endotracheally intubated, and ventilated, and their airways were challenged with histamine. High-resolution computed tomography was used to measure airway luminal areas at baseline and after nebulized histamine. After recovery to baseline, on separate days, dexmedetomidine (0.5 [mu]g/kg) was administered either intravenously or as an aerosol, and the histamine challenge was repeated.

Results: At baseline, histamine constricted the airways to 66 +/- 27% (mean +/- SD) (P < 0.0001) and 59 +/- 30% (P < 0.0001) of maximum on the days dexmedetomidine was administered by intravenous and inhalational means, respectively. After recovery, intravenous administration of dexmedetomidine blocked the histamine-induced bronchoconstriction (87 +/- 30.4% of maximum, compared with histamine alone (P < 0.0001), whereas dexmedetomidine administered by inhalation showed no protective effect (45 +/- 30% of maximum; P < 0.0001 compared with histamine alone).     

Effect of Increasing Perfluorocarbon Dose on ˙Va/˙Q Distribution during Partial Liquid Ventilation in Acute Lung Injury

Background: Although gas exchange during partial liquid ventilation (PLV) depends on perfluorocarbon liquid, the effect of perfluorocarbon dose on the ventilation-perfusion ([spacing dot above]Va/[spacing dot above]Q) distribution is not known. This study investigated how [spacing dot above]Va/[spacing dot above]Q distribution of an acutely injured lung is affected during PLV at increasing perfluorocarbon dose.

Methods: In eight rabbits (3.2 +/- 0.1 kg), acute lung injury (ALI) was created by repeated saline lavage (arterial oxygen partial pressure/fraction of inspired oxygen, 37 +/- 11 mm Hg). Three different doses of perfluorodecalin (9 ml/kg = low dose; 13.5 ml/kg = medium dose; 18 ml/kg = functional residual capacity [FRC] dose) were applied in random order during PLV. [spacing dot above]Va/[spacing dot above]Q distribution at different doses was evaluated by multiple inert gas elimination technique.

Results: Inert gas shunt (63 +/- 21% at ALI) decreased with increasing perfluorocarbon dose (43 +/- 21% at low dose, 29 +/- 10% at medium dose, 11 +/- 9% at FRC dose;P = 0.022). Compared with ALI (0%), the proportion of low [spacing dot above]Va/[spacing dot above]Q units was higher at all tested doses (19 +/- 10, 25 +/- 12, and 34 +/- 18%, respectively; all P < 0.05). Compared with ALI (27 +/- 14%), the proportion of normal [spacing dot above]Va/[spacing dot above]Q units was not increased at low or medium doses but was increased only at the FRC dose (45 +/- 13% ;P = 0.027).     

Isoflurane and halothane attenuate coronary artery constriction evoked by serotonin in isolated porcine vessels and in intact pigs

Serotonin is a vasoconstrictor thought to cause coronary artery constriction in humans. The purpose of this study was to determine if isoflurane and halothane each attenuated coronary artery constriction evoked by serotonin in pigs. Both in vitro and in vivo experimental methods were used. Isolated coronary arteries with an without endothelium were studied in organ chambers in the presence and absence of 2.5% concentrations of the anesthetics. In intact pigs serotonin was infused directly into the left anterior descending coronary arteries to induce constriction. The vasodilator effects of 0.5%, 1.25%, and 2.0% isoflurane and halothane were determined using quantitative angiography. Contractile responses of isolated coronary arteries were depressed by the two anesthetics. Maximum contractile responses to serotonin were as follows: rings with endothelium 45 +/- 5% untreated versus 29 +/- 5% with isoflurane 2.5% (difference between dose-response curves, P less than 0.01) and without endothelium 67 +/- 5% untreated versus 51 +/- 6% with isoflurane 2.5% (P less than 0.001); with endothelium 52 +/- 7% untreated versus 28 +/- 7% with halothane 2.5% (P less than 0.001) and without endothelium 65 +/- 5% untreated versus 40 +/- 6% with halothane 2.5% (P less than 0.001). In intact pigs isoflurane and halothane dilated constricted coronary arteries with and without endothelium at all anesthetic concentrations tested, including concentrations as low as 0.5%. Isoflurane 1.25% increased diameter of vessels with endothelium from 1.5 +/- 0.1 mm to 1.7 +/- 0.1 mm (P less than 0.02) and halothane 1.25% increased diameter from 1.6 +/- 0.1 mm to 1.7 +/- 0.1 mm (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromuscular Relaxants as Antagonists for M sub 2 and M sub 3 Muscarinic Receptors

Background: Neuromuscular relaxants such as pancuronium bind to M sub 2 and M3 muscarinic receptors as antagonists. Blockade of muscarinic receptors in atria of the M2 subtype mediates tachycardia. In the lung, blockade of M2 receptors on parasympathetic nerves potentiates vagally induced whereas blockade of M sub 3 receptors on bronchial smooth muscle inhibits bronchospasm. The current study was designed to quantify the affinity of a series of neuromuscular relaxants for the M2 and M3 muscarinic receptors, which were individually stably transfected in Chinese hamster ovary cell lines.

Methods: Competitive radioligand binding assays determined the relative binding affinities of the neuromuscular relaxants pancuronium, succinylcholine, mivacurium, doxacurium, atracurium, rocuronium, gallamine, and pipecuronium for the muscarinic receptor in the presence of a muscarinic receptor antagonist (sup 3 H-QNB) in membranes prepared from cells individually expressing either the M2 or M3 muscarinic receptor.

Results: All muscle relaxants evaluated displaced3 H-QNB from muscarinic receptors. The relative order of potency for the M2 muscarinic receptor (highest to lowest) was pancuronium, gallamine, rocuronium, atracurium, pipecuronium, doxacurium, mivacurium, and succinylcholine. The relative order of potency for the M3 muscarinic receptor (highest to lowest) was pancuronium, atracurium, pipecuronium, rocuronium, mivacurium, gallamine, succinylcholine, and doxacurium.     

Bronchodilatation and the site of airway resistance in severe chronic bronchitis.

Twenty-one patients with severe chronic bronchitis and emphysema (FEV1 less than 1 1) inhaled 80 microgram of the atropine-like agent ipratropium or placebo in a double-blind study and three hours later inhaled 200 microgram salbutamol. After 80 microgram ipratropium, mean FEV1 was significantly greater than after 200 microgram salbutamol (P less than 0.025), but the difference was only 40 ml and the clinical significance of this difference is unproved. There was no correlation between the patient's response to ipratropium and the response to salbutamol. When salbutamol was administered three hours after ipratropium, the FEV1 rose to higher levels than after either agent alone (P less than 0.01). Studies breathing 80% helium/20% oxygen suggest that ipratropium dilates both large and small airways. There was no correlation between the response to helium/oxygen and the response to either bronchodilator. The results suggest that in severe chronic bronchitis and emphysema ipratropium is at least as effective as salbutamol, and that such patients should have reversibility studies with salbutamol alone, ipratropium alone, and after both agents together. The combination of ipratropium and salbutamol may be clinically useful.     

Sodium cromoglycate and ipratropium bromide in exercise-induced asthma.

In thirteen patients with extrinsic asthma the effects of placebo, sodium cromoglycate, ipratropium bromide, and ipratropium bromide plus sodium cromoglycate were studied in a random double-blind fashion to assess their inhibitory action in exercise-induced asthma (EIA). Exercise testing consisted of steady state running on an inclined treadmill for up to eight minutes. In eight of the 13 patients studied the baseline ratio of expiratory flow at 50% vital capacity (VC) breathing helium-oxygen (V50He) to V50air was over 1.20 and they were called responders; the remaining five patients were called non-responders. There was a significantly lower baseline maximum mid-expiratory flow rate (MMEF) in non-responders (P less than 0.02) as compared to responders but no difference in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). Sodium cromoglycate (P less than 0.02), ipratropium bromide (P less than 0.01), and ipratropium bromide plus spdium cromoglycate (P less than 0.01) all significantly inhibited the percentage fall in FEV1 after exercise in the responders. Ipratropium bromide had no preventive action on non-responders, unlike sodium cromoglycate (P less than 0.05) and ipratropium bromide plus sodium cromoglycate (P less than 0.02). It is postulated that mediator release is an important factor in development of EIA in most extrinsic asthmatics, whereas cholinergic mechanisms are relevant only in those patients in whom the main site of airflow obstruction is in the large central airways.     

Prophylactic Use of Epidural Mepivacaine/Morphine, Systemic Diclofenac, and Metamizole Reduces Postoperative Morphine Consumption after Major Abdominal Surgery

Background: Surgical trauma induces nociceptive sensitization leading to amplification and prolongation of postoperative pain. While preemptive analgesic treatment with numerous agents has been successful in experimental animals, results of human studies remain conflicting. The authors used a multimodal approach for preemptive analgesia before abdominal surgery: diclofenac and metamizole inhibit prostaglandin synthesis, thus influencing peripheral sensitization; epidural local anesthetics induce conduction block, epidural opioids inhibit nociceptive synaptic transmission, and metamizole induces descending inhibition. The interaction of these drugs might suppress spinal nociceptive sensitization and postoperative analgesic demand.

Methods: One hundred forty-two patients scheduled for major abdominal surgery were randomly assigned to one of three groups and studied prospectively. Epidural catheters in groups 1 and 2 were placed at interspaces T8-T10, the position of the catheter was confirmed by epidurography, and sensory testing after administration of 5 ml mepivacaine 1%. Group 1 received 75 mg intramuscular diclofenac, 1000 mg intravenous metamizole, 5.3+/-1 mg epidural morphine, and 15-20 ml mepivacaine 1% 85+/-41 min before skin incision. Epidural analgesia was maintained by injections of 0.1 ml *symbol* kg sup -1 *symbol* h sup -1 mepivacaine 1%. Group 2 patients received the balanced analgesia regimen before wound closure (221+/-86 min after skin incision). Group 3 patients did not receive any study substances. General anesthesia was induced with 5 mg/kg thiopental and 2 micro gram/kg fentanyl and maintained with enflurane and nitrous oxide. Postoperative analgesia consisted of patient-controlled intravenous morphine over 5 days.

Results: Median visual analog scale pain intensities were < 3 cm and did not differ among the groups. Morphine consumption per hour on postoperative day 2 was 0.8+/-0.1 mg/h (group 1) < 1.2+/- 0.1 mg/h (group 2) = 1.1+/-0.1 mg/h (group 3) and cumulative morphine consumption (in mg) on the morning of day 5 was 95+/-9 (group 1) < 111+/-11 (group 2) < 137+/-10 (group 3).     

Ropivacaine, 0.1%, Plus Sufentanil, 0.5 μg/ml, versus Bupivacaine, 0.1%, Plus Sufentanil, 0.5 μg/ml, Using Patient-controlled Epidural Analgesia for Labor: A Double-blind Comparison

Background: This study compared the administration of 0.1% ropivacaine and 0.5 [mu]g/ml sufentanil with that of 0.1% bupivacaine and 0.5 [mu]g/ml sufentanil via patient-controlled epidural analgesia route during labor.

Methods: Two hundred healthy pregnant women at term with a single fetus with a vertex fetal presentation were randomized in a double-blind fashion to receive either 0.1% ropivacaine and 0.5 [mu]g/ml sufentanil or 0.1% bupivacaine and 0.5 [mu]g/ml sufentanil using a patient-controlled epidural analgesia pump (5-ml bolus dose, 10-min locked-out period, no basal infusion). Pain score on a visual analog scale, Bromage score (0-3), level of sensory block, patient-controlled epidural analgesia ratio, drug use, supplemental boluses, and side effects were recorded at 30 min and then hourly. Mode of delivery, duration of first and second stages of labor, umbilical cord pH, Apgar scores of the newborn, and a measure of maternal satisfaction were recorded after delivery.

Results: No differences were seen between the two groups for pain scores on a visual analog scale during labor, volume of anesthetic solution used, mode of delivery, or side effects. Motor block during the first stage of labor was significantly less in the ropivacaine group than in the bupivacaine group (no motor block in 97.8 of patients vs. 88.3%, respectively;P < 0.01). Duration of the second stage of labor was shorter in the ropivacaine group (1.3 +/- 1.0 vs. 1.5 +/- 1.2 h [mean +/- SD];P < 0.05). Maternal satisfaction was greater in the bupivacaine group (91 +/- 13 mm for contraction, 89 +/- 19 mm for delivery on a visual scale: 0 = not satisfied at all, 100 = fully satisfied) than in the ropivacaine group (84 +/- 21 and 80 +/- 25 mm;P < 0.0001). Patients in the ropivacaine group requested more supplemental boluses to achieve analgesia during the second stage of labor than those in the bupivacaine group (29.7 vs. 19.8%, respectively, requested one or more supplemental boluses;P < 0.05).     

Bronchodilator effects of ipratropium bromide and albuterol sulfate among subjects with tetraplegia

Objective: In addition to lung volume restriction, persons with chronic tetraplegia demonstrate obstructive airway physiology evinced by pharmacologically-induced bronchodilation. We previously found independent evidence that anticholinergic agents (ipratropium bromide; IB) and beta-2 adrenergic agonists (albuterol sulfate; AS) were associated with significant bronchodilation in subjects with tetraplegia as determined via spirometry or body plethysmography. Direct comparison of these two classes of agents has received little attention.

Methods: Twelve subjects with chronic tetraplegia completed single dose treatment on alternate days with nebulized IB or AS. Patients underwent pre- and 30-minute post-bronchodilator spirometry, body plethysmography, and impulse oscillation system (IOS) in accordance with established protocols.

Results: Spirometry and specific airway conductance revealed significant bronchodilator responsiveness following both IB and AS. As determined by increases in specific airway conductance post-bronchodilator, IB tended toward greater bronchodilation than AS (71% vs. 47%). IOS revealed a greater reduction in central airway resistance (R20) following IB compared to AS (22% vs. 9%, P?Conclusion: Among subjects with tetraplegia, both IB and AS elicit significant bronchodilation, although the magnitude of the bronchodilator response is greater following IB. This lends support to theory of overriding cholinergic airway tone in tetraplegia. The IOS findings further suggest that the predominant site of action of IB is upon the larger central airways congruent with findings in able-bodied subjects.     

Korean hand acupressure for motion sickness in prehospital trauma care: a prospective, randomized, double-blinded trial in a geriatric population

Patients with trauma or medical illnesses transported to the hospital by ambulance have a frequent incidence of motion sickness. Because the administration of drugs in the ambulance is prohibited by law in Austria, the noninvasive Korean hand acupressure point at K-K9 may be an alternative against nausea and vomiting. We enrolled 100 geriatric patients with minor trauma, randomizing them into a K-K9 group and a sham acupressure group. We recorded visual analog scores (VAS) for nausea and for the patient's overall satisfaction with the treatment, hemodynamic variables, and peripheral vasoconstriction. In the K-K9 group, a significant (P < 0.01) increase in nausea was recorded in all cases: from VAS of 0 mm to 25 +/- 6 mm. A similarly significant (P < 0.01) increase was registered in the sham group: from VAS of 0 mm to 83 +/- 8 mm. However, at the time of arrival in the hospital, nausea scores were significantly different between the K-K9 group and the sham group (P < 0.01). Although all patients had been vasoconstricted at the emergency site before treatment, there was a significant difference (P < 0.01) between groups with regard to the number of vasoconstricted patients at the hospital (4 and 46 constricted and dilated, respectively, in the K-K9 group versus 48 and 2 constricted and dilated, respectively, in the sham group). On arrival in the hospital, a significant difference (P < 0.01) in heart rate was noted between the K-K9 group and the sham group (65 +/- 6 bpm versus 98 +/- 8 bpm). The patients' overall satisfaction with the provided care was significantly higher (P < 0.01) in the K-K9 group (19 +/- 9 mm VAS) than in the sham group (48 +/- 12 mm VAS). Neither group experienced a significant change in blood pressure. K-K9 stimulation was an effective and simple treatment for nausea during emergency care and significantly improved patient satisfaction. IMPLICATIONS: Korean hand acupressure at the K-K9 point was effective in reducing nausea and subjective symptoms of motion sickness in emergency trauma transport of patients at high risk of motion sickness.     

A Multicenter, Randomized, Controlled Trial Comparing Bupivacaine with Ropivacaine for Labor Analgesia

Background: A meta-analysis of studies comparing high doses of bupivacaine with ropivacaine for labor pain found a higher incidence of forceps deliveries, motor block, and poorer neonatal outcome with bupivacaine. The purpose of this study was to determine if there is a difference in these outcomes when a low concentration of patient-controlled epidural bupivacaine combined with fentanyl is compared with ropivacaine combined with fentanyl.

Methods: This was a multicenter, randomized, controlled trial, including term, nulliparous women undergoing induction of labor. For the initiation of analgesia, patients were randomized to receive either 15 ml bupivacaine, 0.1%, or 15 ml ropivacaine, 0.1%, each with 5 [mu]g/ml fentanyl. Analgesia was maintained with patient-controlled analgesia with either local anesthetic, 0.08%, with 2 [mu]g/ml fentanyl. The primary outcome was the incidence of operative delivery. We also examined other obstetric, neonatal, and analgesic outcomes.

Results: There was no difference in the incidence of operative delivery between the two groups (148 of 276 bupivacaine recipients vs. 135 of 279 ropivacaine recipients;P = 0.25) or any obstetric or neonatal outcome. The incidence of motor block was significantly increased in the bupivacaine group compared with the ropivacaine group at 6 h (47 of 93 vs. 29 of 93, respectively;P = 0.006) and 10 h (29 of 47 vs. 16 of 41, respectively;P = 0.03) after injection. Satisfaction with mobility was higher with ropivacaine than with bupivacaine (mean +/- SD: 76 +/- 23 vs. 72 +/- 23, respectively;P = 0.013). Satisfaction for analgesia at delivery was higher for bupivacaine than for ropivacaine (mean +/- SD: 71 +/- 25 vs. 66 +/- 26, respectively;P = 0.037).     

Sigh Improves Gas Exchange and Lung Volume in Patients with Acute Respiratory Distress Syndrome Undergoing Pressure Support Ventilation

Background: The aim of our study was to assess the effect of periodic hyperinflations (sighs) during pressure support ventilation (PSV) on lung volume, gas exchange, and respiratory pattern in patients with early acute respiratory distress syndrome (ARDS).

Methods: Thirteen patients undergoing PSV were enrolled. The study comprised 3 steps: baseline 1, sigh, and baseline 2, of 1 h each. During baseline 1 and baseline 2, patients underwent PSV. Sighs were administered once per minute by adding to baseline PSV a 3- to 5-s continuous positive airway pressure (CPAP) period, set at a level 20% higher than the peak airway pressure of the PSV breaths or at least 35 cm H2O. Mean airway pressure was kept constant by reducing the positive end-expiratory pressure (PEEP) during the sigh period as required. At the end of each study period, arterial blood gas tensions, air flow and pressures traces, end-expiratory lung volume (EELV), compliance of respiratory system (Crs), and ventilatory parameters were recorded.

Results: Pao2 improved (P < 0.001) from baseline 1 (91.4 +/- 27.4 mmHg) to sigh (133 +/- 42.5 mmHg), without changes of Paco2. EELV increased (P < 0.01) from baseline 1 (1,242 +/- 507 ml) to sigh (1,377 +/- 484 ml). Crs improved (P < 0.01) from baseline 1 (40.2 +/- 12.5 ml/cm H2O) to sigh (45.1 +/- 15.3 ml/cm H2O). Tidal volume of pressure-supported breaths and the airway occlusion pressure (P0.1) decreased (P < 0.01) during the sigh period. There were no significant differences between baselines 1 and 2 for all parameters.     

Vaporized Perfluorocarbon Improves Oxygenation and Pulmonary Function in an Ovine Model of Acute Respiratory Distress Syndrome

Background: Perfluorocarbon liquids are being used experimentally and in clinical trials for the treatment of acute lung injury. Their resemblance to inhaled anesthetic agents suggests the possibility of application by vaporization. The authors' aim was to develop the technical means for perfluorocarbon vaporization and to investigate its effects on gas exchange and lung function in an ovine model of oleic acid-induced lung injury.

Methods: Two vaporizers were calibrated for perfluorohexane and connected sequentially in the inspiratory limb of a conventional anesthetic machine. Twenty sheep were ventilated in a volume controlled mode at an inspired oxygen fraction of 1.0. Lung injury was induced by intravenous injection of 0.1 ml oleic acid per kilogram body weight. Ten sheep were treated with vaporized perfluorohexane for 30 min and followed for 2 h; 10 sheep served as controls. Measurements of blood gases and respiratory and hemodynamic parameters were obtained at regular intervals.

Results: Vaporization of perfluorohexane significantly increased arterial oxygen tension 30 min after the end of treatment (P < 0.01). At 2 h after treatment the oxygen tension was 376 +/- 182 mmHg (mean +/- SD). Peak inspiratory pressures (P < 0.01) and compliance (P < 0.01) were significantly reduced from the end of the treatment interval onward.     

Effects of the Beach Chair Position, Positive End-expiratory Pressure, and Pneumoperitoneum on Respiratory Function in Morbidly Obese Patients during Anesthesia and Paralysis

Background: The authors studied the effects of the beach chair (BC) position, 10 cm H2O positive end-expiratory pressure (PEEP), and pneumoperitoneum on respiratory function in morbidly obese patients undergoing laparoscopic gastric banding.

Methods: The authors studied 20 patients (body mass index 42 +/- 5 kg/m2) during the supine and BC positions, before and after pneumoperitoneum was instituted (13.6 +/- 1.2 mmHg). PEEP was applied during each combination of position and pneumoperitoneum. The authors measured elastance (E,rs) of the respiratory system, end-expiratory lung volume (helium technique), and arterial oxygen tension. Pressure-volume curves were also taken (occlusion technique). Patients were paralyzed during total intravenous anesthesia. Tidal volume (10.5 +/- 1 ml/kg ideal body weight) and respiratory rate (11 +/- 1 breaths/min) were kept constant throughout.

Results: In the supine position, respiratory function was abnormal: E,rs was 21.71 +/- 5.26 cm H2O/l, and end-expiratory lung volume was 0.46 +/- 0.1 l. Both the BC position and PEEP improved E,rs (P < 0.01). End-expiratory lung volume almost doubled (0.83 +/- 0.3 and 0.85 +/- 0.3 l, BC and PEEP, respectively; P < 0.01 vs. supine zero end-expiratory pressure), with no evidence of lung recruitment (0.04 +/- 0.1 l in the supine and 0.07 +/- 0.2 in the BC position). PEEP was associated with higher airway pressures than the BC position (22.1 +/- 2.01 vs. 13.8 +/- 1.8 cm H2O; P < 0.01). Pneumoperitoneum further worsened E,rs (31.59 +/- 6.73; P < 0.01) and end-expiratory lung volume (0.35 +/- 0.1 l; P < 0.01). Changes of lung volume correlated with changes of oxygenation (linear regression, R2 = 0.524, P < 0.001) so that during pneumoperitoneum, only the combination of the BC position and PEEP improved oxygenation.     

Respiratory Sites of Action of Propofol: Absence of Depression of Peripheral Chemoreflex Loop by Low-dose Propofol

Background: Propofol has a depressant effect on metabolic ventilatory control, causing depression of the ventilatory response to acute isocapnic hypoxia, a response mediated via the peripheral chemoreflex loop. In this study, the authors examined the effect of sedative concentrations of propofol on the dynamic ventilatory response to carbon dioxide to obtain information about the respiratory sites of action of propofol.

Methods: In 10 healthy volunteers, the end-tidal carbon dioxide concentration was varied according to a multifrequency binary sequence that involved 13 steps into and 13 steps out of hypercapnia (total duration, 1,408 s). In each subject, two control studies, two studies at a plasma target propofol concentration of 0.75 [mu]g/ml (Plow), and two studies at a target propofol concentration of 1.5 [mu]g/ml (Phigh) were performed. The ventilatory responses were separated into a fast peripheral component and a slow central component, characterized by a time constant, carbon dioxide sensitivity, and apneic threshold. Values are mean +/- SD.

Results: Plasma propofol concentrations were approximately 0.5 [mu]g/ml for Plow and approximately 1.3 mg/ml for Phigh. Propofol reduced the central carbon dioxide sensitivity from 1.5 +/- 0.4 to 1.2 +/- 0.3 (Plow;P < 0.01 vs. control) and 0.9 +/- 0.1 l [middle dot] min-1 [middle dot] mmHg-1 (Phigh;P < 0.001 vs. control). The peripheral carbon dioxide sensitivity remained unaffected by propofol (control, 0.5 +/- 0.3; Plow, 0.5 +/- 0.2; Phigh, 0.5 +/- 0.2 l [middle dot] min-1 [middle dot] mmHg-1). The apneic threshold was reduced from 36.3 +/- 2.7 (control) to 35.0 +/- 2.1 (Plow;P < 0.01 vs. control) and to 34.6 +/- 1.9 mmHg (Phigh;P < 0.01 vs. control).     

Selective Pulmonary Vasodilation Induced by Aerosolized Zaprinast

Background: Zaprinast, an inhibitor of guanosine-3',5'-cyclic monophosphate (cGMP)-selective phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators (including inhaled nitric oxide [NO]). The present study was designed to examine the effects of inhaled nebulized zaprinast, alone, and combined with inhaled NO.

Methods: Eight awake lambs with U46619-induced pulmonary hypertension sequentially breathed two concentrations of NO (5 and 20 ppm), followed by inhalation of aerosols generated from solutions containing four concentrations of zaprinast (10, 20, 30, and 50 mg/ml). The delivered doses of nebulized zaprinast at each concentration (mean +/- SD) were 0.23 +/- 0.06, 0.49 +/- 0.14, 0.71 +/- 0.24, and 1.20 +/- 0.98 mg [center dot] kg sup -1 [center dot] min sup -1, respectively. Each lamb also breathed NO (5 and 20 ppm) and zaprinast (0.23 +/- 0.06 mg [center dot] kg sup -1 [center dot] min sup -1) in combination after a 2-h recovery period.

Results: Inhaled NO selectively dilated the pulmonary vasculature. Inhaled zaprinast selectively dilated the pulmonary circulation and potentiated and prolonged the pulmonary vasodilating effects of inhaled NO. The net transpulmonary release of cGMP was increased by inhalation of NO, zaprinast, or both. The duration of the vasodilation induced by zaprinast inhalation was greater than that induced by NO inhalation.