Jerome M. Klafta

Three sudden postoperative respiratory arrests associated with epidural opioids in patients with sleep apnea

Current prominent textbooks on anesthesiology mention sleep apnea syndrome (SAS) only briefly. However, three patients in Illinois (two at one hospital) had sudden postoperative arrests associated with epidural opioids and sleep apnea. We therefore reevaluated the literature, which suggests that epidural opioids are the therapy of choice for patients with sleep apnea (1). Of the 15 patients with SAS reported in the literature, 10 had severe respiratory problems due to postoperative analgesia. Only one report was associated with epidural analgesia, to which we now add three. Based on the experiences we now describe (Case Reports l-3) and review of the literature (Case Reports 4-18), we believe that SAS patients are at particularly high risk of postoperative respiratory depression from any mode of analgesic therapy. Our theory is based on a review of a series of cases and not on mathematical estimates of relative risk. Because of our conclusion, we suggest guidelines for the anesthetic management of such patients.

The unexpected difficult airway and lingual tonsil hyperplasia: a case series and a review of the literature.

Background An unexpected difficult intubation occurs because physical examination of the airway is imperfect in predicting it. Lingual tonsil hyperplasia (LTH) is one risk factor for an unanticipated failed intubation that is not detectable during a routine oropharyngeal examination. The authors attempted to determine the incidence of LTH in unanticipated failed intubation in patients subjected to general anesthesia. Methods Thirty-three patients with unanticipated failed intubation via direct laryngoscopy were subjected to airway examinations and fiberoptic pharyngoscopy to determine the cause(s) of failure. Mouth opening, mandibular subluxation, head extension, thyromental distance, and Mallampati airway class were recorded. Fiberoptic pharyngoscopy was then performed to evaluate the base of the tongue and valleculae. Results Of these 33 patients, none had an airway examination that suggested a difficult intubation. The lungs of 12 patients were difficult to ventilate by mask. In 15 patients, airway measurements were within normal limits with Mallampati class of I or II. Ten patients had a Mallampati class III airway, 6 associated with obesity and 5 with mildly limited head extension. Among the 5 morbidly obese patients, most of the weight was distributed on the lower trunk and body. The 3 remaining patients had a thyromental distance of 6 cm or less but otherwise had a normal airway examination. The only finding common to all 33 patients was LTH observed on fiberoptic pharyngoscopy. Conclusion Lingual tonsil hyperplasia can interfere with rigid laryngoscopic intubation and face mask ventilation. Routine physical examination of the airway will not identify its presence. The prevalence of LTH in adults and the extent of its contribution to failed intubation is unknown.

Subjective, psychomotor, cognitive, and analgesic effects of subanesthetic concentrations of Sevoflurane and nitrous oxide

Background: Sevoflurane is a volatile general anesthetic that differs in chemical nature from the gaseous anesthetic nitrous oxide. In a controlled laboratory setting, the authors characterized the subjective, psychomotor, and analgesic effects of sevoflurane and nitrous oxide at two equal minimum alveolar subanesthetic concentrations. Methods: A crossover design was used to test the effects of two end‐tidal concentrations of sevoflurane (0.3% and 0.6%), two end‐tidal concentrations of nitrous oxide (15% and 30%) that were equal in minimum alveolar concentration to that of sevoflurane, and placebo (100% oxygen) in 12 healthy volunteers. The volunteers inhaled one of these concentrations of sevoflurane, nitrous oxide, or placebo for 35 min. Dependent measures included subjective, psychomotor, and physiologic effects, and pain ratings measured during a cold‐water test. Results: Sevoflurane produced a greater degree of amnesia, psychomotor impairment, and drowsiness than did equal minimum alveolar concentrations of nitrous oxide. Recovery from sevoflurane and nitrous oxide effects was rapid. Nitrous oxide but not sevoflurane had analgesic effects. Conclusions: Sevoflurane and nitrous oxide produced different profiles of subjective, behavioral, and cognitive effects, with sevoflurane, in general, producing an overall greater magnitude of effect. The differences in effects between sevoflurane and nitrous oxide are consistent with the differences in their chemical nature and putative mechanisms of action.

Effects of naloxone on nitrous oxide actions in healthy volunteers

A number of studies have examined the effects of naloxone on nitrous oxide-induced analgesia with conflicting results. In the present study the effects of a relatively high dose of naloxone was examined to determine its effects on nitrous oxide-induced analgesia, as well as on the subjective and psychomotor effects of nitrous oxide. Fourteen subjects participated in a four-session crossover trial in which they received intravenous injections of either saline or 30mg/70kg naloxone 10min into a 35min period in which they were inhaling either 100% oxygen or 30% nitrous oxide in oxygen. Ten minutes after the naloxone administration, subjects were tested on the cold pressor test. Mood and psychomotor performance were also assessed before, during and after the inhalation period. Subjects reported higher pain ratings after the naloxone injection than the saline injection, but there was no evidence of naloxone reversing the analgesic effects of nitrous oxide. Similarly while naloxone also affected mood and impaired psychomotor performance, there was no evidence of naloxone reversing the effect of nitrous oxide on these measures. The results of this study call into question the role of the opioidergic system in mediating various effects of nitrous oxide in humans.

Propofol at conscious sedation doses produces mild analgesia to cold pressor-induced pain in healthy volunteers.

STUDY OBJECTIVE To determine whether subanesthetic doses of propofol have analgesic effects in healthy volunteers. DESIGN Prospective, double-blind, placebo-controlled, randomized, crossover trial. SETTING Human psychomotor performance laboratory within our anesthesia and critical care department. SUBJECTS 12, non-drug abusing volunteers, aged 22 to 38 years. INTERVENTIONS Five drug conditions were used in which a loading injection was followed by a 20-minute infusion period: placebo [saline (Intralipid)] injection, Intralipid infusion; propofol 0.125 mg/kg injection, propofol 12.5 mcg/kg/min infusion; propofol 0.25 mg/kg injection, propofol 25 mcg/kg/min infusion; propofol 0.5 mg/kg injection, propofol 50 mcg/kg/min infusion; fentanyl 1.4 mcg/kg injection (positive control), Intralipid infusion. Five minutes into the infusion period and 115 minutes after the infusion period was terminated, subjects immersed their forearms in ice-cold water for three minutes while pain assessments were recorded. MEASUREMENTS AND MAIN RESULTS Propofol at the two higher doses during part of the first immersion produced a significant reduction (p < 0.05) in pain intensity and bothersomeness ratings. However, relative to fentanyl, the analgesia was mild. Propofol did not affect any ratings on the 15-item short-form McGill Pain Questionnaire, whereas fentanyl reduced 10 of the ratings. CONCLUSION Our laboratory results are consistent with the commonly accepted clinical practice of supplementing propofol with an opioid in conscious sedation procedures to provide a satisfactory level of pain relief.

The effect of sevoflurane and desflurane on upper airway reactivity

Background Although bronchial reactivity can be assessed by changes in airway resistance, there is no well-accepted measure of upper airway reactivity during anesthesia. The authors used the stimulus of endotracheal tube cuff inflation and deflation to assess changes in airway reactivity in patients anesthetized with sevoflurane and desflurane. Methods Sixty-four patients classified as American Society of Anesthesiologists physical status I or II participated in this randomized, double-blind study. Patients were anesthetized with either sevoflurane or desflurane at 1.0 and 1.8 minimum alveolar concentration (MAC). The trachea was stimulated by inflating the endotracheal tube cuff. A blinded observer assessed the severity of patient response to the stimulus and changes in hemodynamic variables. The process was repeated at the second MAC treatment condition. Results At 1.0 MAC, patients anesthetized with desflurane had a more intense response and a greater likelihood of significant coughing and associated hemodynamic changes (both at P < 0.05). At 1.8 MAC, sevoflurane and desflurane both suppressed clinically significant responses to tracheal stimulation. Interrater reliability was excellent for this measure of upper airway reactivity (P < 0.001). Conclusions The assessment of the cough response to tracheal stimulation by endotracheal tube cuff inflation is a reliable and clinically meaningful measure of upper airway reactivity. At 1.0 MAC, sevoflurane is superior to desflurane for suppressing moderate and severe responses to this stimulus.

A dose-response study of the effects of intravenous midazolam on cold pressor-induced pain

The effects of intravenous midazolam (0.75, 1.5, and 3 mg/70 kg) were examined and compared to that of fentanyl (0.1 mg/70 kg; positive control) and saline on pain induced by a cold pressor test. Both sensory and affective components of the pain response were assessed, as there is some evidence that benzodiazepines reduce the affective component. Healthy volunteers (three females, nine males) were enrolled in a prospective, double-blind, randomized, cross-over trial in which mood and psychomotor performance were also examined. Five minutes and 135 min postinjection, subjects immersed their forearm in ice-cold water for 3 min while assessments of pain were recorded. During the first immersion, subjects reported significantly lower pain intensity and bothersomeness ratings after having been injected with fentanyl, relative to the saline and midazolam conditions, which did not differ significantly from each other. Fentanyl and midazolam had prototypical mood altering and psychomotor impairing effects. We conclude that midazolam in our laboratory setting at the doses and route of administration studied had no effects on either the sensory or affective components of the pain experience. (Anesth Analg 1995;80:521-5)

The acute and residual effects of subanesthetic concentrations of isoflurane/nitrous oxide combinations on cognitive and psychomotor performance in healthy volunteers.

A blind, randomized, cross-over trial was conducted to determine the degree of psychomotor/cognitive impairment and the recovery profile produced by combinations of subanesthetic concentrations of isoflurane and nitrous oxide in healthy volunteers. In the experiment, subjects (n = 10) inhaled 100% oxygen-placebo, 30% nitrous oxide in oxygen, and 0.2% and 0.4% isoflurane in oxygen, alone, and in combination with 30% nitrous oxide, in different seesions. Dependent measures included psychomotor and cognitive performance. Impairment was profound with the combination of inhaled anesthetics, and from an analysis of control conditions (the anesthetics alone), it appeared that isoflurane produced more impairment than did nitrous oxide. The time course of recovery was extremely rapid, with subjects returning to control-level functioning 5 min after cessation of the drug inhalation. The drug combination of isoflurane and nitrous oxide appears to be a promising candidate for conscious sedation procedures, although its analgesic and mood-altering effects need to be studied more systematically. (Anesth Analg 1996;82:153-7)

The effects of alcohol history on the reinforcing, subjective and psychomotor effects of nitrous oxide in healthy volunteers

The purpose of this study was to characterize the reinforcing, subjective and psychomotor effects of nitrous oxide in healthy volunteers with different alcohol histories. Subjects were divided into two groups: light drinkers (n = 9) and moderate drinkers (n = 10). A choice procedure was used in which subjects first sampled placebo and a given concentration of nitrous oxide, and then chose between the two. Nitrous oxide concentration varied across the four-session experiment from 10-40%. Besides choice, subjective and psychomotor effects served as dependent measures. The majority of subjective effects of nitrous oxide, and its psychomotor-impairing effects, did not vary as a function of drinking group. However, a Wilcoxon rank sum test showed that the median number of times moderate drinkers chose nitrous oxide (three) was significantly higher than the median number of times light drinkers chose nitrous oxide (one). This study provides suggestive evidence that the reinforcing effects of nitrous oxide are modulated by alcohol history.

Neurological and psychiatric adverse effects of anaesthetics: epidemiology and treatment.

SummaryThe practice of anaesthesia has changed considerably over the past 20 to 30 years owing largely to technological advances in patient monitoring and an expanded and improved pharmacological repertoire. While patient safety in anaesthesia has greatly improved, the risk of neurological and psychiatric adverse effects of anaesthetics remains and is the focus of continued investigation. For example, a great deal of attention has recently been directed at intraoperative awareness. This adverse event can be caused by delivering an inappropriate amount or type of anaesthetic.Another risk of anaesthesia involves drug-induced unpleasant subjective states in patients. Those drugs most frequently associated with these states include ketamine, droperidol and scopolamine. This risk can often be attenuated by careful adjustment of drug dose and the use of adjunctive agents such as benzodiazepines which may produce amnesia of the unpleasant subjective state. While it is well established that modern anaesthetic drugs cause acute impairment of cognition and psychomotor functioning, there is little evidence that these drugs have long term impairing effects. Finally, a particular kind of surgery, cardiac surgery requiring cardiopulmonary bypass, can be associated with adverse neurological and psychiatric sequelae which, while not directly related to anaesthesia, are of intense interest to anaesthesiologists.