Effects of Depth of Propofol and Sevoflurane Anesthesia on Upper Airway Collapsibility, Respiratory Genioglossus Activation, and Breathing in Healthy Volunteers.

BACKGROUND: Volatile anesthetics and propofol impair upper airway stability and possibly respiratory upper airway dilator muscle activity. The magnitudes of these effects have not been compared at equivalent anesthetic doses. We hypothesized that upper airway closing pressure is less negative and genioglossus activity is lower during deep compared with shallow anesthesia. METHODS: In a randomized controlled crossover study of 12 volunteers, anesthesia with propofol or sevoflurane was titrated using a pain stimulus to identify the threshold for suppression of motor response to electrical stimulation. Measurements included bispectral index, genioglossus electromyography, ventilation, hypopharyngeal pressure, upper airway closing pressure, and change in end-expiratory lung volume during mask pressure drops. RESULTS: A total of 393 attempted breaths during occlusion maneuvers were analyzed. Upper airway closing pressure was significantly less negative at deep versus shallow anesthesia (-10.8 ± 4.5 vs. -11.3 ± 4.4 cm H2O, respectively [mean ± SD]) and correlated with the bispectral index (P < 0.001), indicating a more collapsible airway at deep anesthesia. Respiratory genioglossus activity during airway occlusion was significantly lower at deep compared with light anesthesia (26 ± 21 vs. 35 ± 24% of maximal genioglossus activation, respectively; P < 0.001) and correlated with bispectral index (P < 0.001). Upper airway closing pressure and genioglossus activity during airway occlusion did not differ between sevoflurane and propofol anesthesia. CONCLUSIONS: Propofol and sevoflurane anesthesia increased upper airway collapsibility in a dose-dependent fashion with no difference at equivalent anesthetic concentrations. These effects can in part be explained by a dose-dependent inhibiting effect of anesthetics on respiratory genioglossus activity.

Anesthesia and increased hypercarbic drive impair the coordination between breathing and swallowing.

BACKGROUND: Coordination between breathing and swallowing helps prevent aspiration of foreign material into the respiratory tract. The authors examined the effects of anesthesia and hypercapnia on swallowing-breathing coordination. METHODS: In a randomized controlled crossover study, general anesthesia with propofol or sevoflurane was titrated using an up-down method to identify the threshold for suppression of the motor response to electrical stimulation of the forearm. Additional measurements included bispectral index, genioglossus electromyogram, ventilation (pneumotachometer), and hypopharyngeal pressure. During wakefulness and at each level of anesthesia, carbon dioxide was added to increase the end-tidal pressure by 4 and 8 mmHg. A swallow was defined as increased genioglossus activity with deglutition apnea and an increase in hypopharyngeal pressure. Spontaneous swallows were categorized as physiological (during expiration or followed by expiration) or pathological (during inspiration or followed by an inspiration). RESULTS: A total of 224 swallows were analyzed. Anesthesia increased the proportion of pathological swallows (25.9% vs. 4.9%) and decreased the number of swallows per hour (1.7±3.3 vs. 28.0±22.3) compared to wakefulness. During anesthesia, hypercapnia decreased hypopharyngeal pressure during inspiration (-14.1±3.7 vs. -8.7±2 mmHg) and increased minute ventilation, the proportion of pathological swallows (19.1% vs. 12.3%), and the number of swallows per hour (5.5±17.0. vs. 1.3±5.5). CONCLUSIONS: Anesthesia impaired the coordination between swallowing and respiration. Mild hypercapnia increased the frequency of swallowing during anesthesia and the likelihood of pathological swallowing. During anesthesia, the risk for aspiration may be further increased when ventilatory drive is stimulated.

Case report: profound hypotension after anesthetic induction with propofol in patients treated with rifampin.

Rifampin is commonly used for the treatment of tuberculosis and staphylococcal infections, as well as for prevention of infection in cardiac valve and bone surgeries. We report a case of profound hypotension after anesthesia induction with propofol in a patient who was treated with two 600 mg doses of rifampin for prophylaxis of infection before surgery. In a retrospective case-control study of 75 patients, we confirmed this potentially serious drug-drug interaction. After rifampin, there was a significant and prolonged arterial blood pressure reduction when patients received propofol, but not thiopental.

Early use of eyeglasses for myopia predicts long axial length of the eye.

Patients with long axial length (AL) eyes (> 25 mm) are at increased risk of globe perforation during performance of intraconal (retrobulbar) eye block. These patients often require glasses or contact lenses for myopia (nearsightedness) as children or young adults. A history of early correction for myopia might, therefore, be a predictor of long AL eyes. One hundred one patients undergoing cataract surgery had AL measured and answered questions about their use of corrective lenses. We found that a history of correction for myopia as a child or young adult was 82% sensitive and 84% specific for having a measured AL > or = 25 mm. Patients with this history may be at increased risk for globe perforation during intraconal block.

Pentobarbital dose-dependently increases respiratory genioglossus muscle activity while impairing diaphragmatic function in anesthetized rats.

BACKGROUND: Anesthetics depress both ventilatory and upper airway dilator muscle activity and thus put the upper airway at risk for collapse. However, these effects are agent-dependent and may involve upper airway and diaphragm muscles to varying degrees. The authors assessed the effects of pentobarbital on upper airway dilator and respiratory pump muscle function in rats and compared these results with the effects of normal sleep. METHODS: Tracheostomized rats were given increasing doses of pentobarbital to produce deep sedation then light and deep anesthesia, and negative pressure airway stimuli were applied (n = 11). To compare the effects of pentobarbital with those of natural sleep, the authors chronically instrumented rats (n = 10) with genioglossus and neck electromyogram and electroencephalogram electrodes and compared genioglossus activity during wakefulness, sleep (rapid eye movement and non-rapid eye movement), and pentobarbital anesthesia. RESULTS: Pentobarbital caused a dose-dependent decrease in ventilation and in phasic diaphragmatic electromyogram by 11 +/- 0.1%, but it increased phasic genioglossus electromyogram by 23 +/- 0.2%. Natural non-rapid eye movement sleep and pentobarbital anesthesia (10 mg/kg intraperitoneally) decreased respiratory genioglossus electromyogram by 61 +/- 29% and 45 +/- 35%, respectively, and natural rapid eye movement sleep caused the greatest decrease in phasic genioglossus electromyogram (95 +/- 0.3%). CONCLUSIONS: Pentobarbital in rats impairs respiratory genioglossus activity compared to the awake state, but the decrease is no greater than seen during natural sleep. During anesthesia, in the absence of pharyngeal airflow, phasic genioglossus activity is increased in a dose-dependent fashion.

Knowledge-based errors in anesthesia: a paired, controlled trial of learning and retention.

PURPOSE: Optimizing patient safety by improving the training of physicians is a major challenge of medical education. In this pilot study, we hypothesized that a brief lecture, targeted to rare but potentially dangerous situations, could improve anesthesia practitioners' knowledge levels with significant retention of learning at six months. METHODS: In this paired controlled trial, anesthesia residents and attending physicians at Massachusetts General Hospital took the same 14-question multiple choice examination three times: at baseline, immediately after a brief lecture, and six months later. The lecture covered material on seven "intervention" questions; the remaining seven were "control" questions. The authors measured immediate knowledge acquisition, defined as the change in percentage of correct answers on intervention questions between baseline and post-lecture, and measured learning retention as the difference between baseline and six months. Both measurements were corrected for change in performance on control questions. RESULTS: Fifty of the 89 subjects completed all three examinations. The post-lecture increase in percentage of questions answered correctly, adjusted for control, was 22.2% [95% confidence interval (CI) 16.0-28.4%; P < 0.01], while the adjusted increase at six months was 7.9% (95% CI 1.1-14.7%; P = 0.024). CONCLUSION: A brief lecture improved knowledge, and the subjects retained a significant amount of this learning at six months. Exposing residents or other practitioners to this type of inexpensive teaching intervention may help them to avoid preventable uncommon errors that are rooted in unfamiliarity with the situation or the equipment. The methods used for this study may also be applied to compare the effect of various other teaching modalities while, at the same time, preserving participant anonymity and making adjustments for ongoing learning.

Development of peripheral opioid antagonists' new insights into opioid effects.

The recent approval by the US Food and Drug Administration of 2 medications--methylnaltrexone and alvimopan--introduces a new class of therapeutic entities to clinicians. These peripherally acting mu-opioid receptor antagonists selectively reverse opioid actions mediated by receptors outside the central nervous system, while preserving centrally mediated analgesia. Methylnaltrexone, administered subcutaneously, has been approved in the United States, Europe, and Canada. In the United States, it is indicated for the treatment of opioid-induced constipation in patients with advanced illness (eg, cancer, AIDS) who are receiving palliative care, when response to laxative therapy has not been sufficient. Alvimopan, an orally administered medication, has been approved in the United States to facilitate recovery of gastrointestinal function after bowel resection and primary anastomosis. Clinical and laboratory studies performed during the development of these drugs have indicated that peripheral receptors mediate other opioid effects, including decreased gastric emptying, nausea and vomiting, pruritus, and urinary retention. Laboratory investigations with these compounds suggest that opioids affect fundamental cellular processes through mechanisms that were previously unknown. These mechanisms include modifications of human immunodeficiency virus penetration, tumor angiogenesis, vascular permeability, and bacterial virulence.

Haloperidol versus ondansetron for prophylaxis of postoperative nausea and vomiting.

BACKGROUND: Haloperidol is effective for postoperative nausea and vomiting prophylaxis, but there are almost no data comparing it to 5-HT(3) antagonists. METHODS: Two hundred forty-four adults were randomized to receive i.v. haloperidol 1 mg or ondansetron 4 mg, during general anesthesia. Nausea, vomiting, need for rescue, sedation, extrapyramidal effects, QTc intervals, and time to postanesthesia care unit discharge were evaluated with a third-party blind design. RESULTS: There was no intergroup difference in any measure of efficacy or toxicity. Haloperidol and ondansetron subjects (78.2% and 76.8%) had complete response. Postoperatively, prolonged QTc occurred in 28.9% and 22.1% (N.S.). CONCLUSIONS: In a mixed surgical population, the efficacy and toxicity of postoperative nausea and vomiting prophylaxis with haloperidol 1 mg was not significantly different from ondansetron 4 mg.

Haloperidol plus ondansetron versus ondansetron alone for prophylaxis of postoperative nausea and vomiting.

INTRODUCTION: Haloperidol 1 mg and ondansetron 4 mg are equally safe and effective for postoperative nausea and vomiting prophylaxis. We compared the combination to ondansetron alone in a mixed surgical population. METHODS: Two-hundred and sixty-eight adults undergoing general anesthesia received 4 mg ondansetron plus 1 mg haloperidol or saline in this randomized, double-blind protocol. Efficacy and safety data were obtained until 480 min after postanesthesia care unit entry. RESULTS: The combination had more complete responders (76.2% vs 59.2%), less nausea, less rescue, and longer time to rescue. Sedation, time to postanesthesia care unit discharge, and QTc prolongation were not different. No subject had dystonia, akathisia, or serious dysrhythmias. CONCLUSIONS: Postoperative nausea and vomiting prophylaxis with both drugs is significantly more effective and longer lasting than ondansetron alone. There is no detectable increase in side effects.

Stimulation of the posterior cord predicts successful infraclavicular block.

Infraclavicular (IC) block is often performed by localizing one cord within the brachial plexus sheath and placing all the local anesthetic solution at that location. We hypothesized that posterior cord stimulation would be associated with a greater likelihood of IC block success. We enrolled 369 patients scheduled for surgery to the lower arm or hand in a prospective, nonrandomized observational trial. All underwent IC blocks using a standard technique, and the cord stimulated immediately before drug injection was recorded. Motor and sensory functioning were evaluated 15 min after injection. Compared with stimulation of either the lateral or medial cord, stimulation of the posterior cord was associated with rapid onset of motor block in significantly more nerves, as well as a decreased likelihood of block failure (motor and sensory block inadequate to perform surgery). Failure rates were 5.8% for posterior cord, 28.3% for lateral (P < 0.05), and 15.4% for medial (P < 0.05). The differences were highly significant when adjusted for multiple possible confounders, such as gender, body mass index, location of the incision, and level of training of the individual performing the block (P < 0.001, lateral versus posterior; P = 0.003, medial versus posterior). A low failure rate was also predicted by stimulation of more than one cord simultaneously (P < 0.05). We conclude that injection after locating the posterior cord or multiple cords predicts successful IC block.

Rapid absorption of tumescent lidocaine above the clavicles: a prospective clinical study.

BACKGROUND: Tumescent local anesthesia has been adapted for surgery of the face and neck, but there are no data regarding drug absorption when tumescent injection is used in this region. The aim of this study was to characterize the changes in plasma lidocaine concentrations over time when a tumescent solution is injected into the subcutaneous tissue of the neck. The study was carried out in human volunteer subjects, and injection of lidocaine to the thighs provided control data. METHODS: Eight healthy female volunteer subjects were studied twice using a prospective, crossover design. Tumescent lidocaine solution was injected into the subcutaneous tissue of the neck in one session and the thighs in another session. The order of injection was randomized. Blood samples were collected for 14 hours after injection, and the plasma concentration of lidocaine measured. The injected solution consisted of lidocaine 0.1%, NaHCO3 12.5 mEq/L, and epinephrine 1:1,000,000 in normal saline. A standardized dose of lidocaine (7 mg/kg) was used for each injection and no surgical procedure was performed. RESULTS: All subjects completed the study. Subject weight was 66.1 +/- 12.8 kg, body fat was 29.0 +/- 4.7 percent, and body mass index was 23.8 +/- 3.1 kg/m2. The average time to reach peak lidocaine concentration after neck injection was 5.8 hours, whereas peak lidocaine concentration after thigh injection did not occur until 12.0 hours. This difference of 6.2 hours was highly significant (p = 0.009). The average peak concentration after neck injection was 16 percent greater than that after thigh injection (0.94 microg/ml versus 0.81 microg/ml), with the difference approaching significance (p = 0.06). No adverse reactions were noted. CONCLUSIONS: Tumescent injection above the clavicles results in a rapid rise in plasma lidocaine concentration when compared with injection to the lower extremities. Toxic symptoms could occur much earlier than expected for lower extremity tumescent anesthesia. In addition, dangerous plasma levels could occur if tumescent anesthesia in the lower extremities is followed by tumescent injection above the clavicles, because the absorption curves would be superimposed.

Postoperative nausea and vomiting after total intravenous anesthesia with propofol and remifentanil or alfentanil: how important is the opioid?

STUDY OBJECTIVE: To compare the frequency and duration of postoperative nausea and vomiting (PONV) following total intravenous anesthesia (TIVA) with propofol and either remifentanil or alfentanil in outpatients undergoing arthroscopic surgery of the extremities. DESIGN: Randomized, third-party blinded study. SETTING: University medical center. PATIENTS: 100 ASA physical status I and II patients scheduled for arthroscopic surgery of the knee or shoulder. INTERVENTIONS: The anesthesia regimen consisted of a bolus followed by continuous infusion of propofol (2 mg/kg followed by 120 microg/kg/min) and the opioid (remifentanil 0.5 microg/kg followed by 0.1 microg/kg/min or alfentanil 10 microg/kg followed by 0.25 microg/kg/min). Patients breathed 100% oxygen spontaneously through a Laryngeal Mask Airway (or an endotracheal tube when medically indicated). Opioids were titrated to maintain blood pressure and heart rate within 20% of baseline and a respiratory rate of 10 to 16 breaths/min. Propofol was titrated downward as low as possible without permitting patient movement. MEASUREMENTS: Nausea was determined by an 11-point categorical scale and was recorded before surgery and multiple time points thereafter. The times of emetic episodes were recorded. Treatment of PONV was at the discretion of the postanesthesia care unit (PACU) nurses who were blinded to the identity of the opioid used. MAIN RESULTS: Nausea scores were 0 at all time points in over 70% of the patients in each group. None of the 100 patients vomited while in the hospital, and only one patient required antiemetic therapy. CONCLUSION: When propofol-based TIVA is used for arthroscopic surgery, short-acting opioids do not significantly affect the risk of PONV.