Incidence and intensity of myoclonus after induction with etomidate are dose-related, suppressed by pretreatment, and unassociated with seizure-like EEG activity.
Our data demonstrate that intravenous methylnaltrexone can induce laxation and reverse slowing of oral cecal-transit time in subjects taking high opioid dosages. Low-dosage methylnaltrexone may have clinical utility in managing opioid-induced constipation.
Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier and the potential to antagonize the peripherally mediated effects of opioids. The effectiveness of methylnaltrexone in preventing morphine-induced changes in gastrointestinal motility and transit without affecting analgesia was evaluated in humans. Twelve healthy volunteers were given intravenous placebo, placebo plus 0.05 mg/kg morphine, or 0.45 mg/kg methylnaltrexone plus 0.05 mg/kg morphine. Oral-cecal transit time was assessed by the pulmonary hydrogen measurement technique, and analgesia was measured with use of the cold-pressor test. Morphine significantly increased oral-cecal transit time from 104.6 +/- 31.1 minutes (mean +/- SD) to 163.3 +/- 39.8 minutes (p < 0.01). Methylnaltrexone prevented 97% of morphine-induced increase in oral-cecal transit time (106.3 +/- 39.8 minutes; not significant compared with baseline; p < 0.01 compared with morphine alone). Methylnaltrexone did not affect the analgesic effect of morphine on both pain intensity and pain bothersomeness ratings. At a higher dose of morphine (0.1 mg/kg), our preliminary results indicated that 0.45 mg/kg methylnaltrexone also prevented the morphine-induced delay in oral-cecal transit time, with no effect on analgesia. Methylnaltrexone may be a useful adjunct to opioids for the relief of opioid-induced constipation.
A literature review of anesthesia journals revealed several inadequacies and inconsistencies in statistical reports of results of comparison studies with regard to interchangeability of measurement methods. We encourage journal editors to evaluate submissions on this subject carefully to ensure that their readers can draw valid conclusions about the value of new technologies.
We assessed the usefulness of routine laboratory screening of preoperative patients. Computer-readable laboratory, demographic, and discharge diagnostic data were assembled for 2,000 patients undergoing elective surgery over a four-month period, and randomly selected samples of patients were studied. Several tests ordered by protocol and performed by the laboratory at the time of admission were examined in these samples, including complete blood cell count, differential cell count, prothrombin time, partial thromboplastin time, platelet count, six-factor automated multiple analysis, and glucose level. Sixty percent of these routinely ordered tests would not have been performed if testing had only been done for recognizable indications, and only 0.22% of these revealed abnormalities that might influence perioperative management. Chart review indicated that these few abnormalities were not acted on nor did they have adverse surgical or anesthetic consequences. In the absence of specific indications, routine preoperative laboratory tests contribute little to patient care and could reasonably be eliminated.
A number of issues relating to patient education in anesthesia have been addressed in this review and, based upon the available data, some questions can be answered clearly. It is apparent both that a large minority of the American, British, and Australian public is under the misconception that anesthesiologists are not physicians and that the role of the anesthesiologist, both in and out of the operating room, is not fully understood. Many surgical patients, particularly younger ones, have fears about the anesthetic that are distinct from their fears about the surgery, the most common of them relating to waking up prematurely or not at all. Traditional attire for anesthesiologists is preferred by patients but does not appear to significantly influence patient satisfaction. While there are numerous putative advantages to improving patient rapport, good communication as judged by the patient is associated with a lower incidence of malpractice litigation. Preoperative instruction has been demonstrated to have benefit with regard to patient anxiety, postoperative pain, and length of hospitalization. It is also clear that patients' coping behavior varies considerably and strongly influences the usefulness of providing detailed preoperative information. Preoperative teaching should therefore be tailored accordingly. An issue that is less clear concerns the optimal methods for educating patients and the general public. Preliminary evaluation of videotape instruction has yielded somewhat encouraging results, but whether the preoperative visit, supplemented by videotape or in-hospital, on-demand television programming, or computer networks, such as the World Wide Web or home television, are the most effective and practical means for this education remains to be seen. How best to identify in a cost-effective way patients who would most likely benefit from more information is an important question that remains relatively unaddressed. Advances in surgical diagnosis and treatment and critical care have depended upon the development of anesthesia as a specialty. Our ability to continue to develop may depend upon our success in educating the public, politicians, and other health care professionals about what we do. The evaluation of educational methods for disseminating information about anesthesia thus may be important in determining the very future of our specialty and the quality of surgical and pain therapy that patients will receive.
Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier that has the potential to antagonize the peripherally mediated gastrointestinal effects of opioids. In recent trials in human volunteers, we demonstrated that intravenous methylnaltrexone prevented morphine-induced changes in gastrointestinal motility and transit, without affecting analgesia. In this study, 14 healthy volunteers were first given three ascending oral doses of methylnaltrexone to obtain safety and tolerance data (phase A study). In phase B, these subjects were then given single-blind oral placebo and intravenous placebo, followed by randomized, double-blind oral placebo and intravenous morphine (0.05 mg/kg) or oral methylnaltrexone (19.2 mg/kg, an established highest and safe dose based on previous administrations of two smaller doses of 0.64 mg/kg and 6.4 mg/kg in phase A) and intravenous morphine (0.05 mg/kg). Oral-cecal transit time was assessed by the pulmonary hydrogen measurement technique after lactulose ingestion. Morphine significantly increased oral-cecal transit time from 114.6 +/- 37.0 minutes (mean +/- SD) to 158.6 +/- 50.2 minutes (p < 0.001). Oral methylnaltrexone (19.2 mg/kg) completely prevented morphine-induced increase in oral-cecal transit time (110.4 +/- 45.0 minutes; not significant compared with baseline; p < 0.005 compared with morphine alone). These sessions were then followed by single-blind evaluations of descending doses of methylnaltrexone. We observed that 6.4 mg/kg oral methylnaltrexone significantly attenuated the morphine-induced delay in oral-cecal transit time (p < 0.005 compared with morphine alone), and a dose-dependent response was obtained. There was no correlation between oral methylnaltrexone effects on the transit time and the drug plasma concentration, suggesting direct preferential luminal effects of oral methylnaltrexone. Oral methylnaltrexone may have a clinical value in the prevention and treatment of constipation induced by long-term opioid use.
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