Comparison of different quantitative sensory testing methods during remifentanil infusion in volunteers.

BACKGROUND: The aim of this study was to compare thermal and current sensory testing stimuli with respect to opioid responsiveness. METHODS: Eighteen healthy volunteers were randomized in a placebo-controlled, double-blind crossover study to receive an infusion of remifentanil 0.08 micro g kg(-1) min(-1) or saline for 40 min. Test procedures included determination of pain perception thresholds (PPT) and pain tolerance thresholds (PTT) to heat, cold, and current at 5, 250 and 2000 Hz, at baseline and at the end of the infusion. RESULTS: Both current at 5 Hz (PPT 3.69 (SD 2.48) mA vs 2.01 (1.52) mA; PTT 6.42 (2.79) mA vs 3.63 (2.31) mA; P<0.001) and 250 Hz (PPT 4.31 (2.42) mA vs 2.89 (1.57) mA; PTT 7.08 (2.68) mA vs 4.81 (2.42) mA; P<0.001) and heat (PPT 47.4 (2.7) degrees C vs 45.2 (3) degrees C; PTT 51.1 (1.8) degrees C vs 49.7 (1.8) degrees C; P<0.05) detected a significant analgesic effect of remifentanil compared with placebo. No analgesic effect was shown on cold or current at 2000 Hz. The magnitude of responsiveness of current stimuli at 5 Hz and 250 Hz was superior to heat stimuli. CONCLUSION: Both current (5 and 250 Hz) and heat sensory testing detected a significant analgesic effect of a remifentanil infusion compared with saline. There was more response to current testing.

Waste gas exposure to sevoflurane and nitrous oxide during anaesthesia using the oesophageal-tracheal Combitube small adult.

Exposure to sevoflurane (SEV) and nitrous oxide during ventilation using a Combitube (37Fr) small adult (SA) was compared with waste gas exposure using conventional endotracheal tubes. Trace concentrations of SEV and nitrous oxide were assessed using a direct reading spectrometer during 40 gynaecological laparoscopic procedures under general anaesthesia. Measurements were made at the patients' mouth and in the anaesthetists' breathing zone. Mean (SD) concentrations of SEV and nitrous oxide measured at the patients' mouth were comparable in the Combitube SA (SEV 0.6 (0.2) p.p.m.; nitrous oxide 9.7 (8.5) p.p.m.) and endotracheal tube group (SEV 1.2 (0.8) p.p.m.; nitrous oxide 17.2 (10.6) p.p.m.). These values caused comparable contamination of the anaesthetists' breathing zone (SEV 0.6 (0.2) p.p.m. and nitrous oxide 4.3 (3.7) p.p.m. for the Combitube SA group, compared with SEV 0.5 (0.2) p.p.m. and nitrous oxide 4.1 (1.8) p.p.m. for the endotracheal tube group). We conclude that the use of the Combitube SA during positive pressure ventilation is not necessarily associated with increased waste gas exposure, especially when air conditioning and scavenging devices are available.

A follow-up study on occupational exposure to inhaled anaesthetics in Eastern European surgeons and circulating nurses.

OBJECTIVE: Although no dose-response relationship exists for the health risks associated with the occupational exposure to inhaled anaesthetics, public health authorities recommend threshold values. The aim of the present study was to assess whether and to what extent these threshold values are exceeded in surgeons and circulating nurses of an Eastern European university hospital, before and after measures had been taken to reduce occupational exposure. METHODS: At nine workplaces, occupational exposure to nitrous oxide and the volatile anaesthetic used (halothane or isoflurane) was measured within the breathing zones of surgeons and circulating nurses by means of photoacoustic infrared spectrometry. The measurements were carried out in 1996 and were repeated in 1997 after the installation of active scavenging devices at five workplaces, and an air-conditioning system at one workplace. RESULTS: Occupational exposure to nitrous oxide and halothane or isoflurane was lower in 1997 compared with that of 1996. In 1996, 89% of the nitrous oxide values were above the European threshold value of 100 ppm, whereas in 1997 approximately 50% were above this limit. In 1996 the majority of the measurements for the volatile anaesthetics were already below 5 ppm halothane and 10 ppm isoflurane and the number of measurements exceeding these limits was further reduced in 1997. CONCLUSION: The measures taken were effective in reducing waste gas exposure. Nevertheless, further efforts are necessary, especially for nitrous oxide, to reach Western European standards and to minimise possible health risks. These efforts comprise the installation of (active) scavenging devices, air-conditioning systems and new anaesthesia machines at all workplaces, the use of low-flow anaesthesia, the replacement of inhaled anaesthetics by intravenous anaesthetics and an appropriate working technique.

The effect of remifentanil on the heat pain threshold in volunteers.

Remifentanil offers a wide range of clinical uses and has been successfully combined with general anesthetics. However, there are few human experimental studies demonstrating the analgesic property of remifentanil. It was our aim to determine the analgesic effect of remifentanil with regard to dose-dependent increments in a human model of heat pain threshold assessment. Twenty healthy volunteers were randomized in a double-blinded cross-over design to receive an infusion of remifentanil or saline. The stepped infusion was increased every 5 min by 0.01 microg. kg(-1). min(-1) up to 0.17 microg. kg(-1). min(-1)and terminated in case of defined safety limits. Thermal sensory testing of the heat pain threshold was performed every 5 min at the left forearm. The dose-response relationship and the effective dose for at least 50% of the subjects (ED(50)) were determined. Remifentanil led to a clear dose-dependent increase of the heat pain threshold differing significantly from placebo (P < 0.0007). The ED(50) of remifentanil equals 0.05 microg. kg(-1). min(-1) (first quartile 0.025 microg. kg(-1). min(-1) and third quartile 0.06 microg. kg(-1). min(-1)) in this experimental setting. In conclusion, an opioid-mediated analgesic effect of remifentanil was determined in a human heat pain threshold model. The dose of 0.05 microg. kg(-1). min(-1) is an effective and safe increment in healthy volunteers.

Pharmacokinetics of human cerebral opioid extraction: a comparative study on sufentanil, fentanyl, and alfentanil in a patient after severe head injury.

BACKGROUND: The pharmacodynamic differences in time to onset and dissipation of effect of sufentanil, fentanyl, and alfentanil probably result from different rates of blood-brain equilibration. The authors investigated this hypothesis in humans. METHODS: After simultaneous central venous bolus application of sufentanil (10 microg), fentanyl (100 microg), and alfentanil (1,000 microg), arterial and jugular bulb blood samples were drawn simultaneously at 20, 30, 45, 60, 75, 90, 105, 120, 140, 160, 180, 210, 240, 300, 360, and 420 s from 19 patients during the postacute stage of head injury with normal intracranial pressure, cerebral perfusion pressure, and cerebral oxygen metabolism during normocapnia. RESULTS: Peak brain concentration, indicated by equilibrium between arterial and jugular bulb opioid concentrations, was achieved for alfentanil at 45 s, for sufentanil at 5 min, and for fentanyl at 6 min. The corresponding median time intervals (fifth and ninety-fifth percentiles) to reach 50% of peak brain concentration were 15 (14-18), 25 (18-38) and 35 (25-45) s, respectively. Uptake was highest 20 s after bolus and decreased continuously for fentanyl and sufentanil, whereas alfentanil uptake was biphasic. The ratio of the relative amounts of sufentanil, fentanyl, and alfentanil retained in the brain at peak brain concentration was 1x:x6x:x90. CONCLUSIONS: The differences in the time lag between changes in serum concentrations and drug effect after bolus application of nearly equipotent doses of sufentanil, fentanyl, and alfentanil originate from the different times required to reach blood-brain equilibration, mainly depending on different levels and different time profiles of arterial blood concentrations caused by the different tissue distribution volumes.

Effect of pre-emptive hydromorphone administration on postoperative pain relief--a randomized controlled trial.

BACKGROUND AND AIM OF STUDY: Pre-emptive analgesia represents a treatment strategy which tries to prevent the development of pain by inhibiting central reactions to peripheral sensory stimuli. In a prospective randomized double-blind placebo-controlled study, the effect of oral premedication with 4 mg of a slow-release hydromorphone preparation on postoperative piritramide consumption and subjective pain perception is being evaluated. PATIENTS AND METHODS: 96 women undergoing hysterectomy were randomly assigned to four study groups. Patients from groups 1 and 2 received hydromorphone and placebo respectively two hours before surgery, while those from groups 3 and 4 were given the same substances one hour after the end of the operation. Postoperative pain relief was provided by a patient-controlled infusion pump with piritramide. The intensity of postoperative pain as perceived by the patients was quantified on a visual analogue scale. Piritramide consumption and pain scores were recorded at 1 and 24 hours after surgery. Approval of the local Ethics Committee had been obtained beforehand as well as written informed consent from the patients. RESULTS: No significant differences in piritramide consumption were observed in between the four study groups. Visual analogue scale (VAS) ratings at 1 and 24 hours after surgery did not show any significant differences either--irrespective of whether the patients had received hydromorphone or placebo preoperatively or postoperatively. CONCLUSION: In our study, oral administration of 4 mg of slow-release hydromorphone did not show any greater pre-emptive analgesic effect than placebo.

Waste anaesthetic gases induce sister chromatid exchanges in lymphocytes of operating room personnel.

Genotoxicity related to waste anaesthetic gas exposure is controversial. We have investigated the frequency of sister chromatid exchanges in peripheral lymphocytes of operating room personnel exposed to trace concentrations of isoflurane and nitrous oxide. Occupational exposure was recorded using a direct reading instrument. Frequencies of sister chromatid exchanges were measured in lymphocyte cultures of 27 non-smokers working in the operating room and 27 non-smoking controls. Personnel were exposed to an 8-h time-weighted average of nitrous oxide 11.8 ppm and isoflurane 0.5 ppm. After exposure, sister chromatid exchange frequency was increased significantly (mean 9.0 (SD 1.3) vs 8.0 (1.4) in exposed and control personnel, respectively) (P < 0.05). We conclude that exposure to even trace concentrations of waste anaesthetic gases may cause genetic damage comparable with smoking 11-20 cigarettes per day.

Occupational exposure to sevoflurane during sedation of adult patients.

OBJECTIVES: In a field study we evaluated the workplace pollution occurring during conscious sedation with sevoflurane in adults. METHODS: Sevoflurane was given in 100% oxygen at a fresh gas flow rate of 3 l/min via a nasal mask. This was conducted in 25 patients scheduled for surgical procedures performed under regional anesthesia. Trace concentrations of sevoflurane were directly measured every minute in the breathing zone by means of a photoacoustic infrared spectrometer in an operating room with an air turnover of 20 changes/h. RESULTS: The mean sedation time was 49.6+/-20.4 min. The average vaporizer setting of the anesthesia machine was 1.63+/-0.6 vol%, resulting in a patient's mean end-tidal sevoflurane concentration of 0.78+/-0.2 vol%. The 8-h time-weighted average was calculated to be 0.58 ppm sevoflurane. CONCLUSIONS: The trace gas concentrations were low and comparable with values obtained under inhalation induction in adults and children. Although no occupational standard for sevoflurane is currently defined, the measured values are clearly under the standards recommended for enflurane (20 ppm) and isoflurane (10 ppm) by the European health authorities. We conclude that the new anesthesiologic method of conscious sedation with sevoflurane in adults using a nasal mask would not result in a violation of occupational standards, provided that the future value set for sevoflurane would be similar to those recommended for isoflurane or enflurane.

Sister chromatid exchange in human lymphocytes exposed to isoflurane and nitrous oxide in vitro.

The question of whether or not inhalation anaesthetics are genotoxic remains controversial. Therefore, we have studied the in vitro genotoxic potential of isoflurane and nitrous oxide in human lymphocytes. Blood samples were obtained from eight healthy male, non-smoking volunteers, which were incubated and exposed to increasing concentrations of isoflurane (0.0, 0.3, 0.6 and 1.2 mmol litre-1) or 50% nitrous oxide in oxygen. Baseline sister chromatid exchange (SCE) rate per cell was mean 7.65 (SD 1.5) which increased to 9.15 (1.0), 9.55 (1.4) and 9.95 (1.8) SCE/cell during exposure to isoflurane 0.3, 0.6 and 1.2 mmol litre-1, respectively. During 50% nitrous oxide exposure, SCE rate was 9.26 (1.4). The difference between the control and exposed cells was statistically significant (P < or = 0.05). We conclude that exposure to nitrous oxide and subanaesthetic concentrations of isoflurane can produce genetic damage in peripheral lymphocytes in vitro.

Exposure to sevoflurane and nitrous oxide during four different methods of anesthetic induction.

UNLABELLED: The National Institute for Occupational Safety and Health-recommended exposure levels for nitrous oxide exposure are 25 ppm as a time-weighted average over the time of exposure. The exposure limit for halogenated anesthetics (without concomitant nitrous oxide exposure) is 2 ppm. Inhaled sevoflurane provides an alternative to i.v. induction of anesthesia. However, the inadvertent release of anesthetic gases into the room is likely to be greater than that with induction involving i.v. anesthetics. We therefore evaluated anesthesiologist exposure during four different induction techniques. Eighty patients were assigned to one of the induction groups to receive: 1) sevoflurane and nitrous oxide from a rebreathing bag, 2) sevoflurane and nitrous oxide from a circle circuit, 3) propofol 3 mg/kg, and 4) thiopental sodium 5 mg/kg. Anesthesia was maintained with sevoflurane and nitrous oxide via a laryngeal mask. Trace concentrations were measured directly from the breathing zone of the anesthesiologist. During induction, peak concentrations of sevoflurane and nitrous oxide with the two i.v. methods rarely exceeded 2 ppm sevoflurane and 50 ppm nitrous oxide. Concentrations during the two inhalation methods were generally <20 ppm sevoflurane and 100 ppm nitrous oxide. During maintenance, median values were near 2 ppm sevoflurane and 50 ppm nitrous oxide in all groups. Sevoflurane concentrations during inhaled induction frequently exceeded the National Institute for Occupational Safety and Health-recommended exposure ceiling of 2 ppm but mostly remained <20 ppm. Exposure during the maintenance phase of anesthesia also frequently exceeded the 2-ppm ceiling. We conclude that operating room anesthetic vapor concentrations are increased during inhaled inductions and remain increased with laryngeal mask ventilation. IMPLICATIONS: We compared waste gas concentrations to sevoflurane and nitrous oxide during four different induction methods. During inhaled induction with a rebreathing bag or a circle circuit system, waste gas concentrations frequently exceed National Institute for Occupational Safety and Health limits of 2 ppm sevoflurane and 50 ppm nitrous oxide. Therefore, we recommend that people at risk (e.g., women of child-bearing age) should pay great attention when using this technique.

Occupational exposure to sevoflurane and nitrous oxide in operating room personnel.

OBJECT: To quantify the exposure of operating room personnel to sevoflurane and nitrous oxide. DESIGN: Prospective study at a university hospital. METHODS: In 25 patients undergoing elective surgical procedures, anaesthesia was induced with thiopentone/etomidate, vecuronium and fentanyl and maintained with fentanyl, sevoflurance in 35% oxygen and 65% nitrous oxide (N2O). Occupational exposure to sevoflurane and N2O was measured in the breathing zone of one representative of each of three personnel groups (anaesthetist, surgeon, auxiliary nurse) by means of a direct reading instrument using photoacoustic infrared spectrometry. RESULTS: The mean trace concentrations of sevoflurane for the single anaesthetic procedures exceeded the 0.5 ppm level in more than 50% of the measurements. The 2 ppm level was not exceeded in the case of the anaesthetist and the surgeon, but was exceeded in 16% of the measurements for the auxiliary nurse. The level of 25 ppm N2O were exceeded in 28% of the measurements for the anaesthetist and in 16% of these for the surgeon and for the auxiliary nurse. CONCLUSIONS: To keep exposure low, sevoflurane and N2O were used in a modern working environment: a low-leakage anaesthesia machine, high room ventilation rates, scavenging system, no intermittent mask ventilation, low to medium concentrations of sevoflurane, and strict control of the cuff pressure. Nevertheless, exposure could not be kept under NIOSH threshold values in all cases.

Isoflurane waste gas exposure during general anaesthesia: the laryngeal mask compared with tracheal intubation.

We have compared exposure to isoflurane while using the laryngeal mask airway (LMA) during anaesthesia under positive pressure ventilation with exposure while using tracheal intubation. Trace concentrations of isoflurane were measured directly using a highly sensitive photoacoustic infrared spectrometer (Bruel and Kjaer 1302, Denmark) during general anaesthesia in 20 eye surgery procedures. Measurements were made at six locations (three personnel-related, three leakage-related) in the operating theatre. Despite some high isoflurane values (greater than 2000 ppm at one leakage-related measurement point) all measured values at the personnel-related points were low (the majority were less than isoflurane 2 ppm). In the LMA group, mean trace concentrations were slightly higher than in the tracheal tube (ET) group. Mean exposure to isoflurane, expressed as median (range) related to anaesthetic administration, was highest for the auxiliary nurse (0.64 (0.22-26.89) ppm for the LMA compared with 0.31 (0.02-1.07) ppm for the tracheal tube), followed by the anaesthetist (0.50 (0.28-2.28) ppm for the LMA compared with 0.35 (0.02-0.73) ppm for the tracheal tube) and the surgeon (0.36 (0.20-3.93) ppm for the LMA compared with 0.29 (0.01-0.50) ppm for the tracheal tube). We conclude that the use of the LMA in patients undergoing ventilation is not associated necessarily with high concentrations of isoflurane in a modern working environment.