Four-month metacarpal bone mineral density loss predicts radiological joint damage progression after 1†year in patients with early rheumatoid arthritis: exploratory analyses from the IMPROVED study.

AIM: To assess whether in early (rheumatoid) arthritis (RA) patients, metacarpal bone mineral density (BMD) loss after 4 months predicts radiological progression after 1 year of antirheumatic treatment. METHODS: Metacarpal BMD was measured 4 monthly during the first year by digital X-ray radiogrammetry (DXR-BMD) in patients participating in the IMPROVED study, a clinical trial in 610 patients with recent onset RA (2010 criteria) or undifferentiated arthritis, treated according to a remission (disease activity score<1.6) steered strategy. With Sharp/van der Heijde progression ≥0.5 points after 1 year (yes/no) as dependent variable, univariate and multivariate logistic regression analyses were performed. RESULTS: Of 428 patients with DXR-BMD results and progression scores available, 28 (7%) had radiological progression after 1 year. Independent predictors for radiological progression were presence of baseline erosions (OR (95% CI) 6.5 (1.7 to 25)) and early DXR-BMD loss (OR (95% CI) 1.5 (1.1 to 2.0)). In 366 (86%) patients without baseline erosions, early DXR-BMD loss was the only independent predictor of progression (OR (95% CI) 2.0 (1.4 to 2.9)). CONCLUSIONS: In early RA patients, metacarpal BMD loss after 4 months of treatment is an independent predictor of radiological progression after 1 year. In patients without baseline erosions, early metacarpal BMD loss is the main predictor of radiological progression.

A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study.

OBJECTIVES: To assess which treatment strategy is most effective in inducing remission in early (rheumatoid) arthritis. METHODS: 610 patients with early rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) started treatment with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (Disease Activity Score <1.6 after 4 months) tapered prednisone to zero and those with persistent remission after 8 months, tapered and stopped MTX. Patients not in early remission were randomised to receive either MTX plus hydroxychloroquine plus sulfasalazine plus low-dose prednisone (arm 1) or to MTX plus adalimumab (ADA) (arm 2). If remission was present after 8 months both arms tapered to MTX monotherapy; if not, arm 1 changed to MTX plus ADA and arm 2 increased the dose of ADA. Remission rates and functional and radiological outcomes were compared between arms and between patients with RA and those with UA. RESULTS: 375/610 (61%) patients achieved early remission. After 1 year 68% of those were in remission and 32% in drug-free remission. Of the randomised patients, 25% in arm 1 and 41% in arm 2 achieved remission at year 1 (p<0.01). Outcomes were comparable between patients with RA and those with UA. CONCLUSIONS: Initial MTX and prednisone resulted in early remission in 61% of patients with early (rheumatoid) arthritis. Of those, 68% were in remission and 32% were in drug-free remission after 1 year. In patients not in early remission, earlier introduction of ADA resulted in more remission at year 1 than first treating with disease-modifying antirheumatic drug combination therapy plus prednisone.

Outbreak of severe sepsis due to contaminated propofol: lessons to learn.

Nosocomial infections are a frequent concern in healthcare. Despite the available knowledge on nosocomial infections and preventive measures, outbreaks of infections continue to occur. An outbreak of severe sepsis in patients who underwent minor procedures in an operating theatre during two consecutive days is described and analysed in this study. We performed a retrospective cohort study using epidemiological data in order to investigate the source of infection together with microbiological and on-site investigations and interviews. Seven patients met the case definition of postoperative systemic inflammatory response syndrome (SIRS). All other patients operated on over the same period served as controls. Of the risk factors investigated, general anaesthesia and propofol were statistically significant (P=0.003). Klebsiella pneumoniae and Serratia marcescens were cultured from opened vials of propofol, propofol-related devices and from blood cultures from two of the patients. These strains were genotypically indistinguishable. Lapses in aseptic preparation, handling and storage of the propofol were observed, and were the most probable cause of the extrinsic contamination. The daily procedure of handling propofol was not performed according to the manufacturer's recommendations, the main departure being the use of a single-use vial for multiple patients. This study documents the risk of infection due to contaminated propofol and the importance of having written guidelines for its handling.

Evaluation of the electroencephalographic bispectral index during fentanyl-midazolam anaesthesia for cardiac surgery. Does it predict haemodynamic responses during endotracheal intubation and sternotomy?

The bispectral index, a value derived from the electroencephalogram, has been proposed as a measure of anaesthetic effect. The aim of the present study was to evaluate the bispectral index during midazolam-fentanyl anaesthesia for cardiac surgery for its possible role as a predictor of increases in systolic blood pressure during endotracheal intubation and sternotomy. After institutional approval 15 consenting patients, scheduled for elective cardiac surgery, were selected for the study. Anaesthesia was induced in all patients with a loading dose of fentanyl 7.5-10 micrograms kg-1, midazolam 0.15 mg kg-1 and pancuronium 0.1 mg kg-1. After a further bolus dose of fentanyl 10-12.5 micrograms kg-1 prior to the start of incision and sternotomy, maintenance infusion rates of fentanyl 4-6 micrograms kg-1 h-1 and midazolam 0.1 mg kg-1 h-1 were started and continued through surgery at the discretion of the anaesthetist and guided by the presenting clinical and haemodynamic responses. The control of anaesthesia was never based on the value of the bispectral index. The mean bispectral index value decreased from 95.7 (3.1) at base-line to 59.5 (12.0) after induction of anaesthesia and then remained below 70 throughout surgery. However, there was an important interindividual variability in bispectral index values despite standardized dosages of fentanyl and midazolam. There was no significant correlation between the bispectral index values in the pre-intubation and pre-incision period and the changes in systolic blood pressure during endotracheal intubation and sternotomy, respectively. In conclusion, the large intersubject variability in the bispectral index values should be investigated further in the light of the great variability in the clinical effects of midazolam and fentanyl. The lack of significant correlation between the bispectral index values and the haemodynamic responses suggest that the bispectral index, which is a helpful monitor of anaesthetic depth, is not a very reliable monitor of global anaesthetic adequacy during total intravenous anaesthesia with a combination of midazolam and fentanyl in cardiac surgical patients.

A double blind comparison of lidocaine 2% with or without glucose for spinal anesthesia.

The aim of the study was to compare lidocaine 2% plain to lidocaine 2% with glucose 8% for spinal anesthesia. Forty male patients scheduled for urologic surgery participated. The patients were randomly divided into two groups: the plain (P) group received 4 ml of glucose-free lidocaine 2%, the heavy (H) group received 4 ml of lidocaine 2% containing 8% glucose. After the injection, the patients remained in the sitting position for three minutes before they were placed supine. The onset and maximum level of sensory blockade were similar with both preparations (T7-T8). In both groups there were respectively 3 (P) and 4 (H) patients who did not acquire a sensory level above T10. There was a tendency towards a longer duration of sensory blockade in the P group. The patients in both groups developed an almost complete motor blockade within approximately 10 minutes. Duration of complete motorblockade of the lower extremities was significantly shorter for the H group: 59.1 +/- 6.5 minutes (mean +/- SEM) than the P group: 89.5 +/- 6.4 minutes. We consider lidocaine 2% with or without glucose a suitable agent for subarachnoid anesthesia for short procedures. As hyperbaric lidocaine results in a more rapid recovery of motor blockade, it may have advantages for patients in day-case settings.

Thoracic epidural bupivacaine plus sufentanil: high concentration/low volume versus low concentration/high volume.

BACKGROUND AND OBJECTIVES: To compare the postoperative analgesic and side effects of a continuous epidural infusion of bupivacaine with sufentanil: high concentration/low volume versus low concentration/high volume. METHODS: In a prospective study, 30 patients scheduled for thoracic surgery had a thoracic epidural catheter inserted. Postoperative analgesia was provided by a continuous epidural infusion for 3 days. The patients were randomly divided into two groups: the low volume (LV) group (1.5 to 2 mL per hour of a combination of bupivacaine 0.5% with sufentanil 4 micrograms.mL-1) and the high volume (HV) group (6 to 8 mL per hour of a combination of bupivacaine 0.125% with sufentanil 1 microgram.mL-1). RESULTS: The visual analogue scales were not different at rest or with exercise on days 1, 2, or 3. Supplemental analgesia by epidural catheter was necessary in half the patients in both groups. In two patients in the HV group and five patients in the LV group, a PaCO2 greater than mm Hg (7 kPa) was observed the first postoperative hour. Only on day 1 was the mean PaCO2 significantly increased in both groups (5.9 mm Hg [0.7] kPa in the LV group, and 6.0 mm Hg [0.4] kPa in the HV group) compared to the mean preoperative PaCO2 (5.1 mm Hg [0.5] kPa and 4.7 mm Hg [0.6] kPa). Between the groups there was no significant difference in PaCO2 at any time. CONCLUSIONS: With the thoracic epidural administration of bupivacaine and sufentanil for postoperative analgesia, the total dose is more important than the concentration or the volume of the solution.

Ventilatory function and continuous high thoracic epidural administration of bupivacaine with sufentanil intravenously or epidurally: a double-blind comparison.

Variables of ventilation were obtained preoperatively and during the first two postoperative days in 28 patients after thoracic surgery. All patients received 0.5% bupivacaine with epinephrine, 5 micrograms.ml-1 (5-10 ml), through an epidural catheter at the thoracic level supplemented by light general anesthesia. One hour after the initial dose of bupivacaine, patients were randomly allocated to one of two groups: an epidural (EP) sufentanil and an intravenous (IV) sufentanil group. Both groups received 0.125% bupivacaine via continuous epidural infusion postoperatively for three days. In addition, the EP group received 0.83 micrograms.ml-1 sufentanil added to the epidural infusion of 5-10 ml.hour-1, while the IV group received an identical dose of sufentanil via continuous intravenous infusion of 5-10 ml.hour-1. The ventilatory response to 5% CO2 was analyzed preoperatively and on postoperative Days 1 and 2. No significant depression in ventilatory response to CO2 could be detected by measurement of minute ventilation and mouth occlusion pressure at 100 milliseconds (P0.1). Pain measurement was assessed by blinded observers using the Inverse Visual Analog Scale, where 0 signifies most pain and 10 signifies least pain. The mean scores were above 7 in both groups and were attained at similar analgesic requirements. The incidence of side effects was not different. Only the initial mean sufentanil plasma levels in patients of the IV group were higher than those of the EP group. This study shows that the variables of ventilation were not affected by sufentanil administered via the epidural or the intravenous route, and that both techniques provided excellent pain relief when employed to supplement low-dose 0.125% bupivacaine epidurally.

Anaesthesia for laparoscopy. A comparison of five techniques including propofol, etomidate, thiopentone and isoflurane.

This is a report about five anaesthetic techniques for laparoscopy. Propofol and etomidate were used for total intravenous anaesthesia. Propofol, etomidate and thiopentone were used as induction agents prior to inhalational anaesthesia with isoflurane and nitrous oxide. Fentanyl was used for analgesia. Induction with propofol and thiopentone was rapid. Etomidate induction was characterised by myoclonus. Maintenance was smooth with inhalational anaesthesia. Of the groups that received total intravenous anaesthesia, propofol provided stable anaesthesia but required extra bolus doses. Recovery was the most rapid following total intravenous anaesthesia with propofol. Postoperative side effects were much lower after propofol. No difference was observed between the groups with regard to changes in arterial blood pressure and heart rate.