Propofol sedation using Diprifusor target-controlled infusion in adult intensive care unit patients.

This multicentre, non-comparative study investigated the range of target blood propofol concentrations required to sedate 122 adult intensive care patients when propofol was administered using Diprifusor target-controlled infusion systems together with opioid analgesia. Depth of sedation was assessed with a modified Ramsay score and the target blood propofol setting was adjusted to achieve the sedation desired for each patient. A desired level of sedation was achieved for 84% of the sedation period. In postcardiac surgery patients the median time-weighted average propofol target setting was 1.34 microg.ml(-1) (10th - 90th percentiles: 0.79-1.93 microg.ml(-1)). Values in brain injured and general ICU patients were 0.98 (10th - 90th percentiles: 0.60-2.55) microg.ml(-1) and 0.42 (10th - 90th percentiles: 0.16-1.19) microg.ml(-1), respectively. Measured propofol concentrations were generally close to values predicted by the Diprifusor system. Target settings in the range of 0.2-2.0 microg.ml(-1) are proposed for propofol sedation in this setting with titration as required in individual patients.

Recent advances in local anaesthetics for spinal anaesthesia.

Although local anaesthesia is mentioned in historical manuscripts, it is only a hundred years since Bier first reported the intrathecal use of local anaesthetic agents. This has been followed by a rapid progression in the art and science of spinal anaesthesia. Isomerically pure agents with favorable clinical profiles, such as ropivacaine and levobupivacaine are now available. Spinal anaesthesia is commonly used in a variety of situations, including orthopaedic, abdominal, gynaecological surgery, Caesarean section and the relief of pain in childbirth. Hyperbaric solutions of local anaesthetics appear to produce more consistent results than plain solutions and the addition of other drugs, such as opioids and clonidine may improve analgesia. In addition to traditional spinal anaesthesia, local anaesthetics are now being evaluated in continuous spinal anaesthesia and combined epidural-spinal anaesthesia. This article reviews clinical experience with levobupivacaine and ropivacaine. Compared with levobupivacaine, ropivacaine generally produces a less intense motor block of shorter duration, which has advantages for earlier mobilization and discharge from hospital and may be particularly useful in obstetrics and ambulatory surgery.

Spinal anaesthesia: comparison of plain ropivacaine 5 mg ml(-1) with bupivacaine 5 mg ml(-1) for major orthopaedic surgery.

BACKGROUND: Ropivacaine provides effective spinal anaesthesia for total hip arthroplasty. This study was designed to compare the efficacy and safety of plain ropivacaine with plain bupivacaine for spinal anaesthesia in patients undergoing total hip arthroplasty. METHODS: Sixty-six patients, ASA I or II, were randomized to receive an intrathecal injection of one of two local anaesthetic solutions. Group R (n=32) received 3.5 ml of ropivacaine 5 mg ml(-1) (17.5 mg). Group B (n=34) received 3.5 ml of bupivacaine 5 mg ml(-1) (17.5 mg). The onset and duration of sensory block at dermatome level T10, maximum upper and lower spread of sensory block and the onset, intensity and duration of motor block were recorded, as were safety data. RESULTS: Onset of motor and sensory block was rapid with no significant differences between the two groups. The median time of onset of sensory block at the T10 dermatome was 2 min (range 2-5 min) in Group R and 2 min in Group B (range 2-9 min). The median duration of sensory block at the T10 dermatome was 3.0 h (range 1.5-4.6 h) in Group R and 3.5 h (2.7-5.2 h) in Group B (P<0.0001). The median duration of complete motor block (modified Bromage Scale 3) was significantly shorter in the ropivacaine group compared with the bupivacaine group (2.1 vs 3.9 h, P<0.001). CONCLUSIONS: Intrathecal administration of either 17.5 mg plain ropivacaine or 17.5 mg plain bupivacaine was well tolerated and an adequate block for total hip arthroplasty was achieved in all patients. A more rapid postoperative recovery of sensory and motor function was seen in Group R compared with Group B.

Eradication of endotracheal tube biofilm by nebulised gentamicin.

OBJECTIVE: To compare the efficacy of gentamicin, nebulised via the endotracheal tube (ET), with that of parenteral cefotaxime or parenteral cefuroxime in preventing the formation of ET biofilm. SETTING: General intensive care units in two university teaching hospitals. DESIGN: The microbiology of ET biofilm from 36 ICU patients eligible to receive antibiotic prophylaxis was examined. Peak and trough tracheal concentrations of gentamicin, cefotaxime or cefuroxime were measured in each patient group, on the 2nd day of intubation. PATIENTS: Twelve patients received gentamicin (80 mg) nebulised in 4 ml normal saline every 8 h, 12 cefotaxime (1 g, 12 hourly) and 12 cefuroxime (750 mg, 8 hourly). Prophylaxis was continued for the duration of intubation. MEASUREMENTS AND RESULTS: Samples of tracheal secretions were taken on the 2nd day of ventilation for determination of antibiotic concentrations. Following extubation, ETs were examined for the presence of biofilm. Pathogens considered to be common aetiological agents for VAP included Staphylococcus aureus, enterococci, Enterobacteriaceae and pseudomonads. While microbial biofilm was found on all ETs from the cephalosporin group, microbial biofilm of these micro-organisms was found on 7 of the 12 ET tubes from patients receiving cefotaxime [ S. aureus (4), pseudomonads (1), Enterobacteriaceae (1), enterococcus (1)] and 8 of the 12 ET tubes from patients receiving cefuroxime [Enterobacteriaceae (6), P. aeruginosa (1) and enterococcus (1)]. While microbial biofilm was observed on five ETs from patients receiving nebulised gentamicin, none of these were from pathogens for ventilator-associated pneumonia (VAP). Tracheal concentrations of both cephalosporins were lower than those needed to inhibit the growth of pathogens recovered from ET tube biofilm. The median (and range) concentrations for cefotaxime were 0.90 (<0.23-1.31) mg/l and 0.28 (<0.23-0.58) mg/l for 2 h post-dose and trough samples, respectively. Two hours post-dose concentrations of cefuroxime (median and range) were 0.40 (0.34-0.83) mg/l, with trough concentrations of 0.35 (<0.22-0.47) mg/l. Tracheal concentrations (median and range) of gentamicin measured 1 h post-nebulisation were 790 (352-->1250) mg/l and then, before the next dose, were 436 (250-1000) mg/l. CONCLUSION: Nebulised gentamicin attained high concentrations in the ET lumen and was more effective in preventing the formation of biofilm than either parenterally administered cephalosporin and therefore may be effective in preventing this complication of mechanical ventilation.

Post-operative analgesia following total knee replacement: an evaluation of the addition of an obturator nerve block to combined femoral and sciatic nerve block.

BACKGROUND: Femoral and sciatic nerve block may not provide complete post-operative analgesia following total knee replacement. This study was designed to evaluate whether the addition of an obturator nerve block to combined femoral and sciatic nerve block improves the quality of post-operative analgesia following primary total knee replacement. METHODS: Sixty patients were randomised into one of two groups: combined femoral and sciatic nerve block with 15 ml 0.75% ropivacaine to each nerve or combined femoral and sciatic nerve block with 15 ml 0.75% ropivacaine to each nerve and an obturator nerve block with 5 ml 0.75% ropivacaine. RESULTS: Peripheral nerve blocks were successful in 85% of patients. The group which received the obturator nerve block showed a significant increase in the time until their first request for analgesia (mean 257.0 vs. 433.6 min) and a significant reduction in the total requirements for morphine throughout the study period (mean 83.8 vs. 63.0 mg) (P<0.05). There were no systemic or neurological sequelae in any of the groups. CONCLUSIONS: The addition of an obturator nerve block to femoral and sciatic blockade improved post-operative analgesia following total knee replacement.

Total knee replacement: a comparison of ropivacaine and bupivacaine in combined femoral and sciatic block.

BACKGROUND: Femoral and sciatic nerve block may improve post-operative analgesia following total knee replacement. OBJECTIVES: To compare the post-operative analgesia following primary total knee replacement provided by spinal anaesthesia alone or in combination with femoral and sciatic nerve block with bupivacaine or ropivacaine. METHODS: Seventy-five patients were randomised into one of three groups: spinal anaesthesia only; spinal anaesthesia and combined femoral and sciatic nerve block with 1 mg x kg(-1) bupivacaine 7.5 mg x ml(-1) to each nerve; spinal anaesthesia and combined femoral and sciatic nerve block with 1 mg x kg(-1) ropivacaine 7.5 mg x ml(-1) to each nerve. RESULTS: The mean (SD) time to first morphine request was significantly prolonged for both groups receiving combined femoral and sciatic block, 912 (489) min for the bupivacaine group and 781 (394) min for the ropivacaine group (P<0.001) compared with 413 (208) min for the group receiving spinal anaesthesia alone. Morphine consumption was significantly reduced in both groups receiving combined femoral and sciatic block. There were no systemic or neurological sequelae in any of the groups. CONCLUSIONS: Femoral and sciatic blockade following intrathecal bupivacaine/diamorphine provided superior analgesia when compared with intrathecal bupivacaine/diamorphine alone. There were no significant clinical differences between the group receiving bupivacaine 7.5 mg x ml(-1) and the group receiving ropivacaine 7.5 mg x ml(-1).

Evaluation of long-term efficacy and safety of transdermal fentanyl in the treatment of chronic noncancer pain.

The objective of this international, multicenter, open-label trial was to assess the efficacy and safety of up to 12 months of therapy with transdermal therapeutic system (TTS) fentanyl in patients (n = 532) with chronic noncancer pain. The trial was completed by 301 (57%) of the patients. The main outcome measures were pain control assessment, global treatment satisfaction, patient preference for TTS fentanyl, and quality of life. The mean dose of transdermal fentanyl (TDF) increased from 48 to 90 microg/h during a period of 12 months. During treatment, on average 67% of patients within the efficacy analysis group (n = 524) reported very good, good, or moderate pain control. Global satisfaction (very good or good) was also stable at 42%. The majority (86%) of patients reported a preference for TDF over their previous treatment (P < .001, binomial test). Short Form 36 quality-of-life scores improved from baseline for bodily pain. The most frequent treatment-related adverse events were nausea (31%), constipation (19%), and somnolence (18%). With regard to opioid-specific adverse events (respiratory depression [< 1%], adrenal insufficiency [< 1%], drug abuse/dependence [1%], and opioid withdrawal syndrome [3%]), these were extremely rare and, with the exception of opioid withdrawal syndrome, none was considered definitively related to the treatment. Long-term treatment with TDF provided a stable degree of pain control in the majority of patients with moderate to severe chronic noncancer pain. It was preferred by the majority of patients compared with their previous opioid medication. Overall, long-term treatment with TDF was generally well tolerated, particularly in view of the low incidence of potentially serious side effects such as drug abuse/dependence and respiratory depression. However, at present, it is important that patients receiving TDF should still be subject to careful assessment and monitoring.

Health assessment and its relationship to nursing practice in New Zealand.

Health assessment has been an integral component of nursing education in Australia for over a decade. New Zealand has only recently embarked down this path and might benefit from the Australian experience. This article will discuss health assessment in the context of three issues currently topical in nursing in New Zealand. The issues are annual registration based on evidence of competence to practice, a review of undergraduate curricula, and the development of nurse practitioner/advanced nurse practitioner roles. The meaning of the concept 'health assessment' is also clarified in order to provide consistency as new initiatives in nursing are currently being developed.

Intrathecal ropivacaine for total hip arthroplasty: double-blind comparative study with isobaric 7.5 mg ml(-1) and 10 mg ml(-1) solutions.

This study was designed to evaluate the efficacy and safety of two concentrations of intrathecal ropivacaine, 7.5 and 10 mg ml(-1), in patients undergoing total hip arthroplasty. One hundred and four patients, ASA I-III, were randomized to receive an intrathecal injection of one of two concentrations of isobaric ropivacaine. Group 1 (n=51) received 2.5 ml of 7.5 mg ml(-1) ropivacaine (18.75 mg). Group 2 (n=53) received 2.5 ml of 10 mg ml(-1) ropivacaine (25 mg). The onset and offset of sensory block at dermatome level T10, maximum upper and lower spread of sensory block and the onset, intensity and duration of motor block were recorded, as were safety data. Onset of motor and sensory block was rapid with no significant differences between the two groups. The median time of onset of sensory block at the T10 dermatome was 2 min (range 1-25 min) in Group 1 and 2 min (range 1-21 min) in Group 2. The median duration of sensory block at the T10 dermatome was 3.0 h (range 0.5-4.2 h) in Group 1 and 3.4 h (1.1-5.9 h) in Group 2 (P=0.002). The median duration of complete motor block was significantly prolonged (P<0.05) in Group 2 compared with Group 1 (1.9 vs 1.2 h, respectively). Anaesthetic conditions were excellent in all but one patient. Intrathecal ropivacaine, in doses of 18.75 and 25 mg, was well tolerated and provided effective anaesthesia for total hip arthroplasty.

Efficacy and uptake of ropivacaine and bupivacaine after single intra-articular injection in the knee joint.

The efficacy of ropivacaine 100 mg (5 mg ml(-1)), 150 mg (7.5 mg ml(-1)) and 200 mg (10 mg ml(-1)) and bupivacaine 100 mg (5 mg ml(-1)) given by intra-articular injection into the knee after the end of surgery was studied in 72 ASA I-II patients scheduled for elective knee arthroscopy under general anaesthesia in a randomized, double-blind study. Kapake (paracetamol 1 g and codeine 60 mg) was given as a supplementary analgesic. Pain scores were assessed 1-4 h after surgery and a verbal rating scale of overall pain severity was assessed on second postoperative day. Ropivacaine or bupivacaine concentrations were determined in peripheral venous plasma up to 3 h after injection in eight patients in each group. Verbal rating pain scores were lower with ropivacaine 150 mg compared with bupivacaine 100 mg (P<0.05). There was a tendency for lower analgesic consumption and pain scores with all doses of ropivacaine (not significant). The mean (SD) maximum total plasma concentrations of ropivacaine were 0.64 (0.25), 0.78 (0.43), and 1.29 (0.46) mg litre(-1) after 100, 150 and 200 mg. The corresponding unbound concentrations were 0.018 (0.009), 0.024 (0.020) and 0.047 (0.022) mg litre(-1). Both were proportional to the dose. The maximum total concentration after bupivacaine 100 mg was 0.57 (0.36) mg litre(-1). The time to reach maximum plasma concentration was similar for all doses and varied between 20 and 180 min. All concentrations were well below the threshold for systemic toxicity.

Lyngbyabellin B, a toxic and antifungal secondary metabolite from the marine cyanobacterium Lyngbya majuscula.

Lyngbyabellin B (1) was isolated from a marine cyanobacterium, Lyngbya majuscula, collected near the Dry Tortugas National Park, Florida. This new cyclic depsipeptide displayed potent toxicity toward brine shrimp and the fungus Candida albicans. The planar structure was deduced using 1D and 2D NMR spectroscopic methods, and the stereochemistry is proposed through a combination of NMR and chiral GC/MS analysis.

Serum mitochondrial aspartate transaminase activity after isoflurane or halothane anaesthesia.

We examined the effect of halothane or isoflurane anaesthesia on hepatic function in 30 ASA I-III patients aged 18-70 yr undergoing lumbar discectomy. Hepatic function was assessed before anaesthesia, at the end of surgery, and at 3, 6, 24 and 48 h after surgery using routine enzyme tests of hepatic function and mitochondrial aspartate transaminase (mAST) activity. Although serum mAST activities increased after surgery in both groups of patients, these increases were statistically significantly greater in the group that received halothane. The groups were similar with regard to other tests of hepatic function. Calculation of the ratio of serum enzyme activities compared to baseline values suggested that mAST is a sensitive marker of anaesthetic-induced hepatic injury.

Two new malyngamides from a Madagascan Lyngbya majuscula.

The lipid extract of a Madagascan Lyngbya majuscula has yielded malyngamides Q and R, both amides of 7-methoxytetradec-4-enoic acid. The isolation of these metabolites was accomplished using preparative liquid chromatography, with final purification through repetitive reversed-phase HPLC. Structure elucidation was accomplished utilizing 1D and 2D NMR spectroscopic characterization of the natural products and comparisons with malyngamides A and B. DPFGSE 1D NOE data suggested a different geometrical stereochemistry at C-6 in malyngamides Q and R from that observed for malyngamide A, as well as the other known malyngamides. The Z stereochemistry was confirmed for malyngamide R by measurement of key diagnostic (3)J(CH) couplings utilizing the HSQMBC pulse sequence. The absolute stereochemistry of C-4' ' of the pyrrolidone ring was defined by chiral GCMS analysis of serine released by ozonolysis and acid hydrolysis.

The efficacy and safety of epidural infusions of levobupivacaine with and without clonidine for postoperative pain relief in patients undergoing total hip replacement.

UNLABELLED: We assessed the efficacy and tolerability of epidural infusions of levobupivacaine, levobupivacaine plus clonidine, and clonidine for postoperative analgesia in 86 patients undergoing total hip replacement. For each group, an epidural cannula was inserted before surgery and 15 mL of 0.75% plain levobupivacaine was administered. Three hours later, an epidural infusion (6 mL/h) of levobupivacaine 0.125% (L), levobupivacaine 0.125% plus clonidine 8.3 microg/mL (LC) or clonidine alone (8.3 microg/mL) (C) was initiated. Morphine consumption was recorded for the following 24 h as were visual analog pain scores and the degree of sensory and motor blockade. The mean (median) morphine consumption was lowest in the combination group (LC),14 (7) mg; higher in the clonidine group (C), 23 (21) mg; and highest in the levobupivacaine group (L), 37 (36) mg (P = 0.022). The median times until the first request for analgesia which were 2. 9, 5.9, and 12.5 h for Groups L, C, and LC, respectively (P < or = 0. 01). There were no statistical differences among the groups regarding the maximum degree of postoperative motor blockade. On average, the systolic blood pressure in the two clonidine groups was slightly lower than in those from the levobupivacaine group. We conclude that the epidural administration of a combination of levobupivacaine plus clonidine is well tolerated and gives better analgesia than either drug used alone. IMPLICATIONS: In patients undergoing total hip replacement, the addition of the alpha(2)-adrenergic agonist clonidine to epidural infusions of levobupivacaine significantly improved postoperative analgesia.

Implications of endotracheal tube biofilm for ventilator-associated pneumonia.

OBJECTIVE: To determine the relationship between, and antibiotic resistance of, endotracheal tube (ET) biofilm and pulmonary pathogens in ventilator-associated pneumonia (VAP). SETTING: General intensive care units in two university teaching hospitals. DESIGN: The microbiology of ET biofilm and tracheal samples from patients with and without VAP were compared. For individual patients, matching pairs of pathogens were confirmed as identical and characterised for antibiotic susceptibility. PATIENTS: 40 intensive care unit patients - 20 with VAP, 20 without VAP as control. The duration of intubation (median and range) was 6.5 days (3-17) and 5 days (2-10), respectively. MEASUREMENTS AND RESULTS: Samples of tracheal secretions were taken during ventilation for bacteriological culture. Following extubation, ETs were examined for the presence of biofilm. Isolates of high pathogenic potential included Staphylococcus aureus, enterococci, Enterobacteriaceae, pseudomonads and Candida spp. Where the same microorganism was found on tracheal and ET samples by phenotyping, these were confirmed as identical by genotyping and characterised for antibiotic susceptibility in both the free floating and biofilm forms. Seventy per cent of patients with VAP had identical pathogens isolated from both ET biofilm and tracheal secretions. No pairing of pathogens was observed in control patients (p < 0.005). Susceptibility data for these pairs show that the ET acts as a reservoir for infecting microorganisms which exhibit significantly greater antibiotic resistance than their tracheal counterparts. CONCLUSION: This investigation provides further evidence for the role of ET biofilm in VAP. The difficulty in eradicating an established microbial biofilm using antibiotics implies that increased attention must be directed towards modification of the ET to prevent or substantially reduce biofilm formation.