Does functional ability in the postoperative period differ between remifentanil- and fentanyl-based anesthesia?

STUDY OBJECTIVES: To compare patients' functional ability in the 24-hour postoperative period following a remifentanil compared to a hypnotic-fentanyl-treated anesthesia regimen using a 24-Hour Functional Ability Questionnaire. DESIGN: Prospective, 1:1 single-blind, randomized, controlled effectiveness study. SETTING: Multicenter study including 156 hospitals and ambulatory surgery facilities. PATIENTS: 2438 patients (1496 outpatients and 942 inpatients) 18 years of age or older, scheduled for elective surgeries under general endotracheal anesthesia, with an expected duration of unconsciousness of > or =30 minutes. INTERVENTIONS: Patients were randomized to receive either intravenous remifentanil (0.5 microg/kg/min for induction and intubation; with the infusion rate decreased to 0.25 microg/kg/min after intubation) or fentanyl (administered according to anesthesiologists' usual practice) as the opioid during surgery. Concomitant hypnotic drugs were propofol and/or isoflurane (with or without nitrous oxide) titrated according to protocol. Transition analgesia with either morphine or fentanyl was given in the remifentanil patients and at the discretion of the anesthesiologists in the fentanyl patients. MEASUREMENTS: A validated set of measurements of functional ability, rather than more traditional clinical psychological methods, to compare the recovery of patients from remifentanil- and fentanyl-treated anesthetic regimens up to 24 hours after surgery. MAIN RESULTS: Remifentanil was statistically superior to fentanyl for the four functional assessments evaluated: walking without dizziness, thinking clearly, concentration, and communicating effectively. These differences reflect events occurring within the first 24 hours after anesthesia and surgery. CONCLUSIONS: A remifentanil-treated anesthetic demonstrated earlier return to some functions than a fentanyl-treated technique. Although functional assessment is a field that is still in its infancy, a questionnaire to assess functional ability during the 24 hours after anesthesia may provide more practical information about anesthetic recovery than previously used, traditional psychomotor evaluations.

Propofol in an emulsion of long- and medium-chain triglycerides: the effect on pain.

IMPLICATIONS: In a test of two formulations of propofol for induction, patients experienced less pain with the formulation in Intralipid (Propofol-Lipuro 1%) than with Diprivan 1%.

Better health while you wait: a controlled trial of a computer-based intervention for screening and health promotion in the emergency department.

STUDY OBJECTIVE: We evaluate a computer-based intervention for screening and health promotion in the emergency department and determine its effect on patient recall of health advice. METHODS: This controlled clinical trial, with alternating assignment of patients to a computer intervention (prevention group) or usual care, was conducted in a university hospital ED. The study group consisted of 542 adult patients with nonurgent conditions. The study intervention was a self-administered computer survey generating individualized health information. Outcome measures were (1) patient willingness to take a computerized health risk assessment, (2) disclosure of behavioral risk factors, (3) requests for health information, and (4) remembered health advice. RESULTS: Eighty-nine percent (470/542) of eligible patients participated. Ninety percent were black. Eighty-five percent (210/248) of patients in the prevention group disclosed 1 or more major behavioral risk factors including current smoking (79/248; 32%), untreated hypertension (28/248; 13%), problem drinking (46/248; 19%), use of street drugs (33/248; 13%), major depression (87/248; 35%), unsafe sexual behavior (84/248; 33%), and several other injury-prone behaviors. Ninety-five percent of patients in the prevention group requested health information. On follow-up at 1 week, 62% (133/216) of the prevention group patients compared with 27% (48/180) of the control subjects remembered receiving advice on what they could do to improve their health (relative risk 2.3, 95% confidence interval 1.77 to 3.01). CONCLUSION: Using a self-administered computer-based health risk assessment, the majority of patients in our urban ED disclosed important health risks and requested information. They were more likely than a control group to remember receiving advice on what they could do to improve their health. Computer methodology may enable physicians to use patient waiting time for health promotion and to target at-risk patients for specific interventions.

Is there a learning curve associated with the use of remifentanil?

UNLABELLED: This study prospectively determined whether there was a learning curve with the use of remifentanil, as indicated by decreased hemodynamic variability, improved recovery profile, and decreased incidence of opioid-related adverse events with increasing experience. Patients undergoing diverse surgical procedures (outpatient [n = 1340] and inpatient [n = 560]) were enrolled by investigators (n = 190) who had no previous experience with remifentanil use. Each investigator enrolled 10 patients. A standardized protocol for administration of remifentanil was used. Data were analyzed to determine differences between the first three patients and the last three patients enrolled for each anesthesiologist in the study. There were no differences in hemodynamic variables between the first triad and the last triad in either outpatients or inpatients. Requirements for hypnotic drugs and the doses of remifentanil used were also similar between groups. Analgesic medications administered at the end of surgery and in the postanesthesia care unit (PACU) were similar between groups, except that the last triad in the outpatient group received smaller doses of fentanyl compared with the first triad. Times to response to verbal command, tracheal extubation, and operating room discharge did not differ between groups. However, patients in the last triad undergoing outpatient surgery had shorter times to eligibility for PACU discharge, but times to eligibility for discharge home did not differ. The overall incidence of all adverse events (i.e., hypotension, hypertension, muscle rigidity, respiratory depression, apnea, nausea, and vomiting) was less in the last triad as compared with the first triad. When analyzed separately, only the incidence of vomiting (in the outpatient group) was decreased in the last triad as compared with the first triad. This study suggests that there is a learning curve that aids reduction of minor adverse effects associated with the use of analgesic medications administered at the end of surgery in outpatients, which might have reduced the incidence of postoperative vomiting and the duration of PACU stay. IMPLICATIONS: This study demonstrated that anesthesiologists rapidly acquire the ability to use remifentanil with limited experience. However, there is a learning curve that aids reduction of minor adverse effects associated with the use of analgesic medications administered at the end of surgery in outpatients, which might have reduced the incidence of postoperative vomiting and the duration of postanesthesia care unit stay.

Sensitivity of diagnostic and localization tests for pheochromocytoma in clinical practice.

BACKGROUND: Although pheochromocytomas are believed to account for fewer than 0.3% of all cases of hypertension, aggressive diagnostic and surgical intervention is recommended whenever a pheochromocytoma is suspected because uncontrolled catecholamine release from the tumors can lead to catastrophic consequences. Many biochemical diagnostic and imaging localization tests exist for detecting pheochromocytomas. We sought to evaluate the sensitivity of these tests used over a 35-year period at a single institution. METHODS: Thirty-five patients with complete medical records who had pathologically confirmed pheochromocytomas between 1962 and 1997 at the University of Chicago Hospitals were identified. Sensitivity and 95% confidence intervals were calculated for 12 laboratory diagnostic tests and 5 imaging studies. RESULTS: The most sensitive laboratory diagnostic tests in our study were plasma total catecholamines (95%) and urine total metanephrines (100%). Testing for urine vanillylmandelic acid, while less expensive and easier to perform than many other tests, had a slightly lower sensitivity (89%). The most sensitive imaging tests in the study were magnetic resonance imaging (100%) and iodine I-131 metaiodobenzylguanidine scintigraphy (100%). The more often used computed tomography had only 88% sensitivity. Localization was safely and successfully performed on two pregnant patients using magnetic resonance imaging and ultrasound. CONCLUSIONS: By properly choosing from the wide array of laboratory diagnostic and imaging tests, pheochromocytomas can be identified and localized with nearly 100% sensitivity. These tests should be performed in any patient for whom the diagnosis of pheochromocytoma is being considered.

Safe and cost-effective preoperative preparation of patients with pheochromocytoma.

This study examines the management of patients diagnosed with pheochromocytoma at a major academic teaching hospital. The findings indicate that most patients can be safely managed as outpatients preoperatively, resulting in significantly shorter hospitalizations and no adverse sequelae.

Effects of enteric-coated methylnaltrexone in preventing opioid-induced delay in oral-cecal transit time.

BACKGROUND: Methylnaltrexone is the first peripheral opioid receptor antagonist. It has the potential to prevent or reverse the peripherally mediated gastrointestinal effects of opioids. In previous human volunteer trials, we demonstrated that oral uncoated methylnaltrexone prevented morphine-induced delay in gastrointestinal transit time. METHODS: This trial consisted of two studies: a pilot study and a controlled study. The lactulose hydrogen breath test was used to measure the oral-cecal transit time. RESULTS: In the pilot study with three subjects, an oral dose of 6.4 mg/kg enteric-coated methylnaltrexone effectively reversed the effects of morphine, producing transit times shorter than baseline levels. Subsequently, in the controlled study with another nine subjects, the transit time increased after intravenous morphine administration in all nine subjects, and the lower dose (3.2 mg/kg) of enteric-coated methylnaltrexone completely prevented the morphine-induced change in oral-cecal transit time in all nine subjects. Morphine significantly increased oral-cecal transit time from baseline level of 96.7 +/- 54.1 minutes (mean +/- SD) to 155.0 +/- 53.6 minutes (P = .014). After enteric-coated methylnaltrexone and morphine, the transit time returned to the baseline level (93.3 +/- 56.0 minutes; P = .55 compared with placebo). Plasma concentrations after 6.4 mg/kg and 3.2 mg/kg enteric-coated methylnaltrexone were substantially lower compared with those after 6.4 mg/kg of the uncoated formulation. CONCLUSION: Our results suggest that there is a prevailing direct and local luminal effect of enteric-coated methylnaltrexone and that the enteric-coated formulation exerts its gut pharmacologic actions more efficiently than the uncoated formulation.

Comparing methods of clinical measurement: reporting standards for bland and altman analysis.

UNLABELLED: In this era of medical technology assessment and evidence-based medicine, evaluating new methods to measure physiologic variables is facilitated by standardization of reporting results. It has been proposed that assessing repeatability be followed by assessing agreement with an established technique. If the "limits of agreement" (mean bias +/- 2SD) are not clinically important, then one could use two measurements interchangeably. Generalizability to larger populations is facilitated by reporting confidence intervals. We identified 44 studies that compared methods of clinical measurement published during 1996 to 1998 in seven anesthesia journals. Although 42 of 44 (95.4%) used the limits of agreement methodology for analysis, several inadequacies and inconsistencies in reporting the results were noted. Limits of agreement were defined a priori in 7.1%, repeatability was evaluated in 21.4%, and relationship (pattern) between difference and average was evaluated in 7.1%. Only one of the articles reported confidence intervals. A computer macro for the Minitab statistical package (State College, PA) is described to facilitate reporting of Bland and Altman analysis with confidence intervals. We propose standardization of nomenclature in clinical measurement comparison studies. IMPLICATIONS: 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.

Methylnaltrexone for reversal of constipation due to chronic methadone use: a randomized controlled trial.

CONTEXT: Constipation is the most common chronic adverse effect of opioid pain medications in patients who require long-term opioid administration, such as patients with advanced cancer, but conventional measures for ameliorating constipation often are insufficient. OBJECTIVE: To evaluate the efficacy of methylnaltrexone, the first peripheral opioid receptor antagonist, in treating chronic methadone-induced constipation. DESIGN: Double-blind, randomized, placebo-controlled trial conducted between May 1997 and December 1998. SETTING: Clinical research center of a university hospital. PARTICIPANTS: Twenty-two subjects (9 men and 13 women; mean [SD] age, 43.2 [5.5] years) enrolled in a methadone maintenance program and having methadone-induced constipation. MAIN OUTCOME MEASURES: Laxation response, oral-cecal transit time, and central opioid withdrawal symptoms were compared between the 2 groups. RESULTS: The 11 subjects in the placebo group showed no laxation response, and all 11 subjects in the intervention group had laxation response after intravenous methylnaltrexone administration (P<.001). The oral-cecal transit times at baseline for subjects in the methylnaltrexone and placebo groups averaged 132.3 and 126.8 minutes, respectively. The average (SD) change in the methylnaltrexone-treated group was -77.7 (37.2) minutes, significantly greater than the average change in the placebo group (-1.4 [12.0] minutes; P<.001). No opioid withdrawal was observed in any subject, and no significant adverse effects were reported by the subjects during the study. CONCLUSIONS: 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.

Design and reliability of pediatric HealthQuiz: preliminary report of a comprehensive, computerized, self-administered child health assessment.

The time available for pediatric ambulatory visits is rarely sufficient to permit a truly comprehensive health assessment. We hypothesized that a reliable, computerized, self-administered questionnaire could be designed to screen for a full range of pediatric health issues and provide a comprehensive health database for pediatric patients. An age- and gender-specific pediatric questionnaire of 478 questions was formatted to elicit only a "Yes," "No," or "Not Sure" response and structured in a branched, decision-tree format. The initial draft was reviewed for content by pediatric experts in Canada and the United States and revised in accordance with their suggestions. The questionnaire was divided into two modules, Medical Peds, covering biomedical issues and Prevent Peds, covering prevention, psychosocial, educational, and safety topics. Cognitive interviews were carried out with 132 parents in pediatric ambulatory care centers in Chicago and Halifax, with use of scripted and nonscripted probe questions, to ensure comprehensibility among patients with widely varying educational levels and health knowledge. Reliability was tested in 100 parents of children aged 1 month to 12 years, through use of five different test-retest sequences. Respondents' impressions were surveyed on completion of the procedure. Following content reviews, and cognitive and reliability testing, the total bank of questions was reduced to 375. As a result of the use of branching logic, individual parents answered an average of 111 Prevent Peds and 144 Medical Peds questions. Average time required to complete the entire questionnaire was 13 minutes for Prevent Peds and 19 minutes for Med Peds. Retesting within 36 hours showed an overall 97% concordance of response pairs in the Medical Peds and Prevent Peds questionnaires. There were no statistically significant differences in test-retest reliability between different sequence formats used, (e.g., HealthQuiz followed by personal interview, or HealthQuiz vs. HealthQuiz). A few questions that frequently elicited "Not Sure" responses were eliminated. As a result, the majority of questions elicited either a "Yes" or "No" response. Pediatric HealthQuiz identified a wide spectrum of child health problems that are often overlooked in routine health visits. Parents completing Pediatric HealthQuiz indicated a high degree of satisfaction with the procedure. Most reported that they believed the information would improve their child's health care.

Use of electronic mail for postoperative follow-up after ambulatory surgery.

The authors report on a patient who used electronic mail to report satisfactory recovery from ambulatory surgery and anesthesia. The potential benefits and pitfalls of using electronic mail for patient follow-up and communication, as well as research purposes, are reviewed. Potential benefits include cost savings, ease in collecting quality improvement data, and the potential for increased reporting of unpleasant events. Potential pitfalls include lack of universal access (with racial and socioeconomic differentials), privacy and security concerns, and potential slow responses to messages that might require emergent responses or actions.

Second step: testing-outcome measurements.

Despite worldwide enthusiasm for endoscopic surgery, this new technology is now on the top of McKinlay's "product life circle curve." Critical questions are being asked about its benefits and burdens, but the concepts applied and the methodologies used for technology assessment are in a similar position as endoscopic surgery and need a critical evaluation. (1) There are incorrect and outdated concepts for the scientific basis of surgery (surgical theory) including the basic sciences involved; biomedicine still dominates, but assessment of outcome after operations is no longer possible without clinical epidemiology and social psychology. (2) Based on an outdated scientific theory for surgery, an outdated concept of disease is still propagated. It is denoted as mechanical and is based solely on biomedicine. Human subjects are reduced to biologic machines, and outcomes measurement excludes most dimensions of functioning and well-being. To achieve a valid result for outcome measures, a hermeneutic approach must be combined with the mechanical approach. (3) Based on an outdated model of disease, the outcomes used in endoscopic surgery rely too much on traditional measures, such as mortality rate, complication rate, hospital stay, and especially an endless list of biochemical mediators. Their alterations during the perioperative period have not yet been shown to be related to clinical or hermeneutic outcomes. A new method of assessment for clinical trials in endoscopic surgery and for other surgical problems is outlined, such as for surgical infections and for surgical oncology. It includes an index of recovery and objective health status assessed by the doctor, a quality-of-life self-report by the patient, and the true endpoint concept as a critical weighting of both types of outcome by patients and doctors.

Reducing myoclonus after etomidate.

BACKGROUND: The authors hypothesized that myoclonus after etomidate is dose-related, could be suppressed when small doses of etomidate were administered before induction, and is unassociated with seizure-like activity on electroencephalogram (EEG). METHODS: Three studies were performed. In the first study, 36 men were randomly assigned to receive 0.025, 0.050, 0.075, 0.100, 0.200, or 0.300 mg/kg of etomidate. In a second crossover study, eight men were randomly allocated to receive either a pretreatment dose of 0.050 mg/kg etomidate or placebo 50 s before 0.300 mg/kg etomidate was injected. EEG was recorded for subjects in the first two studies. In a third study, 60 patients were randomly allocated to one of three pretreatment doses of etomidate: 0.030, 0.050, or 0.075 mg/kg before 0.300 mg/kg was given. RESULTS: In Study 1, myoclonus was not observed after 0.025 or 0.050 mg/kg etomidate. One volunteer had myoclonus after 0.075 mg/kg and another after 0.100 mg/kg etomidate; three had myoclonus after 0.200 mg/kg; and five after 0.300 mg/kg. Incidence of myoclonus was dose-related (P < or = 0.01). In Study 2, two volunteers (25%) with etomidate pretreatment had mild myoclonus compared to six (75%) with placebo pretreatment (P < or = 0.05). EEG changes, other than delta waves, were not seen during myoclonic epochs. In Study 3, myoclonus was less likely after the small pretreatment doses (0.030 or 0.050 mg/kg) than after the large dose (0.075 mg/kg, P < or = 0.01). CONCLUSIONS: Incidence and intensity of myoclonus after induction with etomidate are dose-related, suppressed by pretreatment, and unassociated with seizure-like EEG activity.

Solvent for etomidate may cause pain and adverse effects.

We tested the hypothesis that the solvent for etomidate was a factor in the incidence of pain and other side effects after injection, and that these were associated with histamine release. Nine of 10 volunteers who received etomidate in a propylene glycol formulation reported moderate to severe pain on injection; only one of 10 subjects who received a lipid emulsion formulation reported mild pain (P < 0.05). The incidence of venous sequelae in the injected vein over the next 8 days was 50% in the propylene glycol group and 0% in the lipid emulsion group (P < 0.05). In one volunteer in the propylene group, there was a 13-fold increase in histamine concentrations and in one subject a four-fold increase. In the lipid emulsion group, no volunteer had an increase in histamine concentrations > 1 ng ml-1. We conclude that etomidate formulated in propylene glycol may cause direct injury to vascular endothelium resulting in pain and venous sequelae, whereas etomidate in lipid emulsion does not. There was no relationship between pain or venous sequelae and histamine release.