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Background In this prospective, randomized, double-blind, placebo-controlled study, we investigated the effect of pregabalin on oxycodone consumption, postoperative confusion, and pain in elderly cardiac surgery patients. Methods Seventy patients, aged ≥75 yr, were randomized to receive either 150 mg of pregabalin before operation and 75 mg of pregabalin twice daily for 5 postoperative days or placebo. Pain intensity was measured with the Verbal Rating Scale (VRS). When pain intensity was ≥2 on the VRS, patients received oxycodone either i.v. (0.05 mg kg-1) or orally (0.10–0.15 mg kg-1). Postoperative confusion was measured with the Confusion Assessment Method for the intensive care unit (CAM-ICU). Postoperative pain was assessed by a telephone interview 1 and 3 months after operation. Results Cumulative consumption of parenteral oxycodone during 16 h after extubation was reduced by 44% and total oxycodone consumption from extubation to the end of the fifth postoperative day was reduced by 48% in the pregabalin group. Time to extubation was 138 min shorter and CAM-ICU scores were significantly lower on the first postoperative day in the placebo group, although there was no significant difference with respect to the Mini-Mental State Examination or the Richmond Agitation Sedation Score. The incidence of pain during movement was significantly lower in the pregabalin group at 3 months postoperative. Conclusions The administration of pregabalin reduced postoperative opioid consumption after cardiac surgery reduced the incidence of confusion on the first postoperative day and increased time to extubation when compared with placebo. Three months after operation, patients in the pregabalin group experienced less pain during movement.

Functional magnetic resonance imaging has been widely used to study brain activation induced either by specific sensory stimulation or motor or cognitive task performance. We demonstrate that functional magnetic resonance imaging can provide information of brain regions involved in opioid-induced central nervous system effects. The reproducibility of the responses in the predefined regions of interest was confirmed by repeated boluses of ultra-short acting mu-opioid receptor agonist remifentanil and saline. We report spatially and temporally detailed information after remifentanil administration. Areas rich in mu-opioid receptors showed strong activations, whereas primary somatosensory cortex that has the lowest density of mu-opioid receptors showed negligible activation. The cingulate, orbitofrontal, posterior parietal and insular cortices, and amygdala showed activation, which was temporally closely related to most subjective sensations that were strongest at 80 to 90 s after drug administration. These areas belong to a circuitry that modulates the affective experience of sensory stimuli.

Background Ropivacaine 2 mg ml −1 (0.2%) provides longer-lasting analgesia after deflation of the tourniquet cuff, with fewer side-effects, than lidocaine 5 mg ml −1 (0.5%) after i.v. regional anaesthesia (IVRA). Whether ropivacaine 2 mg ml −1 also exerts this advantage over prilocaine 5 mg ml −1 , the local anaesthetic of choice in IVRA in most European countries was investigated in this study. Methods Sixty outpatients scheduled for forearm or hand surgery received IVRA with 40 ml of ropivacaine 2 mg ml −1 (Ropi) or prilocaine 5 mg ml −1 (Prilo) in a randomized, double-blinded fashion. The development and recovery of pin-prick analgesia and motor power of the hand, as well as ropivacaine and prilocaine plasma concentrations ( n =30), were assessed during and after operation. Results Anaesthesia for surgery was adequate in both groups. Pin-prick analgesia was achieved at a similar rate, except in the radial nerve distribution area where at 10 min 60% of Ropi and 90% of Prilo patients had analgesia ( P =0.017). At 10 min 100 and 97% had motor block of the hand in the Ropi and Prilo groups, respectively. Recovery of the sensory block in all innervation areas was already observed 2 min after the tourniquet cuff release. At 10 min after releasing the tourniquet cuff 31% of the Ropi patients and none of the Prilo patients still had analgesia in the median nerve distribution ( P =0.004). At 12 min, 42% in the Ropi group and none in the Prilo group had decreased grip strength. After the release of the tourniquet, mean plasma concentrations of ropivacaine were higher than those of prilocaine. The highest individual concentration of ropivacaine was 1.65 μg ml −1 and that of prilocaine 0.6 μg ml −1 . None of the Ropi patients experienced any symptoms of local anaesthetic toxicity. Conclusions Compared with prilocaine 5 mg ml −1 , analgesia in IVRA with ropivacaine 2 mg ml −1 developed slightly more slowly, while motor block developed at a similar rate. After the release of the tourniquet, sensation recovered quickly and at a similar rate in the two groups, except for a slightly slower recovery after ropivacaine in the innervation area of the median nerve, but no surgically useful extended analgesia after the cuff deflation was observed. Despite a 60% lower milligram-dose, ropivacaine plasma concentrations were markedly higher than those of prilocaine.

Although retrobulbar and peribulbar regional anaesthetic techniques are used (by both anaesthesiologists and ophthalmologists) in various types of eye surgery, topical anaesthesia of the conjunctiva and cornea, followed—as needed—by sub-Tenon's block, is now common in routine cataract surgery. Intracameral administration of local anaesthetic by the ophthalmologist is also performed. Sedation during ophthalmic surgery is distinctly lighter than for other surgery because it is essential that the patient remains alert and can cooperate with the surgeon. Continuous insufflation of oxygen-enriched air is needed to ascertain that CO 2 has been flushed away. With a catheter placed into the nostril, the patient (whose head is draped and ‘hidden') can have the end-tidal CO 2 monitored. Finger index (FI), a palpation method that assesses the ease of performing retrobulbar block, is introduced. Because of the risk of life-threatening complications in ophthalmic regional anaesthesia, the services of an anaesthesiologist must be available and training of anaesthesia residents in ophthalmic regional anaesthesia is highly recommended.

Certain drugs or chemicals may be added to local anesthetic solutions to enhance the tissue spread of the local anesthetic. Perhaps the best known is glucose (dextrose) added to spinal anesthesia solution to make it hyperbaric and to allow the local anesthetic to spread in the cerebrospinal fluid by gravity, as needed. Hyaluronidase addition has been abandoned in almost all other regional anesthetic blocks except ophthalmologic blocks. Hylauronidase is expensive and it is not devoid of side-effects and, therefore, as low concentrations as possible are recommended. Even as low concentration as 3.75 IU/mL of hyaluronidase is able to enhance the spread of the concentrated local anesthetic solution, causing analgesia and akinesia without damage to the eye muscles. Hyaluronidase addition to local anesthetic solutions is used to some extent also in dermatological surgery. The spread of local anesthetics for topical skin analgesia and anesthesia is promoted by influencing the penetrating property physically (eutectic mixture), electrically (iontophoresis), and encapsulating in liposomes. The penetration (spread) of the local anesthetic through the skin is significantly faster with iontophoresis and liposomes in comparison with the eutectic mixture of local anesthetics.

Background Acetaminophen (paracetamol) enhances the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is a weak inhibitor of cyclooxygenase (COX), and its combination with an NSAID may augment COX inhibition-related side effects. Methods Ten healthy male volunteers (21–30 yr) were given diclofenac 1.1 mg kg−1 alone, a combination of propacetamol 30 mg kg−1 (which is hydrolysed to 50% acetaminophen) and diclofenac 1.1 mg kg−1 or placebo intravenously in a double blind, crossover study. Platelet function was assessed at 5 min, 90 min and 22–24 h by photometric aggregometry, platelet function analyser (PFA-100™) and by measuring the release of thromboxane B2 (TxB2). Analgesia was assessed with the cold pressor test. Results Platelet aggregation induced with arachidonic acid was fully inhibited by both diclofenac alone and the combination at the end of the 30-min drug infusion. Propacetamol augmented the inhibition by diclofenac at 90 min (P=0.014). At 22–24 h, platelet function had fully recovered. TxB2 release was inhibited by the combination of propacetamol and diclofenac at 90 min in comparison with diclofenac alone (P=0.027). PFA-100™ detected no difference in platelet function between these two groups. No analgesic effect was detected with the cold pressor test. Conclusions The combination of propacetamol and diclofenac inhibits platelet function more than diclofenac alone. This should be considered when assessing the risk of surgical bleeding.

Objective: To assess the prevalence and implementation of ‘do not resuscitate' orders, nowadays called ‘do not attempt resuscitation' (DNAR) orders and living wills among patients suffering in-hospital cardiac arrest (CA) in whom cardiopulmonary resuscitation was not initiated. Materials and methods: A prospective survey of CA patients conducted in four secondary hospitals during 2000–2001. The information collected included the presence of DNAR and a living will and the patients sociodemographic and disease factors and the reasons for not initiating resuscitation when no DNAR order was present. Data on the resuscitated patients were collected according to the Utstein recommendations (analyzed and published separately) and used for comparison. Results: During the study period, 1486 patients suffered CA without resuscitation being initiated. Data collection was successful in 1143 patients (77%), who were included in the study. Most of the patients (84.5%) had a DNAR order. The prevalence of DNAR orders differed between the participating hospitals ( P 0.001), and between the wards of the hospital, with most DNAR orders in the cardiac care unit (100%) and medical wards (87%). The patients designated as DNAR were likely to be older ( P 0.01) and of poorer functional status ( P 0.001). Reasons for abstaining from resuscitation without a DNAR order were unwitnessed arrest (27%) and terminal disease (66%). Living wills were uncommon (1.5%). Patients with a living will were likely to have a DNAR order ( P 0.01). Conclusion: Most patients who suffered in-hospital CA without resuscitation had a DNAR order, and, for those who did not, terminal disease and medical futility were evident in most cases. Living wills were uncommon, but they appeared to have had some impact on treatment.

Objective: To investigate the safety and efficacy of thrombolytic treatment for an acute myocardial infarction (AMI) immediately after resuscitation in the out-of-hospital setting. Design: Retrospective. Setting: A middle-sized urban city (population 540 000) served by a single emergency medical system using a tiered response with physicians in field. Patients and methods: Sixty-eight patients with an initial diagnosis of AMI who received thrombolytic treatment in an out-of-hospital setting after cardiac arrest and cardiopulmonary resuscitation (CPR) between January 1st 1994 and December 31st 1998. An ECG and the myocardial enzymes (CK, CK-MB, Troponin-T) were used to diagnose AMI. Myocardial reperfusion was assessed by resolution of the ST-segment elevation. Side effects and complications were studied. The quality of secondary survival was evaluated. The Utstein style was used for a uniform style of reporting the cardiac arrest data. Results: The accuracy of prehospital diagnosis was found to be excellent. Retrospective analysis revealed that thrombolytic therapy had been appropriately administered in 64 (94%) of the 68 patients actually treated. Reperfusion was achieved in 71% of the patients. Haemorrhagic complications were few, and included intracranial haemorrhage (one patient), gastrointestinal bleeding (two patients), bleeding from the puncture site (one patient) and epistaxis (one patient). The incidence of hypotension during streptokinase infusion was 22%. Sixty-three (93%) of the patients were admitted alive to the hospital, with 36 subsequently surviving to discharge. Conclusions: Thrombolytic treatment is a safe and effective treatment in AMI even after out-of-hospital cardiopulmonary resuscitation.

Acute administration of a neurosteroid 5beta-pregnan-3alpha-ol-20-one induced a greater impairment in motor performance of the selectively bred alcohol-sensitive (ANT) than alcohol-insensitive (AT) rats. This difference was not associated with the sensitivity of gamma-aminobutyrate type A (GABA(A)) receptors, as 5alpha-pregnan-3alpha-ol-20-one (allopregnanolone) decreased the autoradiographic signals of t-butylbicyclophosphoro[35S]thionate binding to GABA(A) receptor-associated ionophores more in the brain sections of AT than ANT rats. Nor was the difference associated with baseline levels of neuroactive progesterone metabolites, as 5alpha-pregnan-3,20-dione (5alpha-DHP) and 5alpha-pregnan-3alpha-ol-20-one were lower in the ANT rats. After ethanol (2 g/kg, i.p.) administration and the subsequent motor performance test, the increased brain concentrations of these metabolites were still lower in the ANT than AT rats, although especially in the cerebellum the relative increases were greater in the ANT than AT rats. The present data suggest that the mechanisms mediating neurosteroid-induced motor impairment are susceptible to genetic variation in rat lines selected for differences in ethanol intoxication.

Epidural administration of drugs is becoming more common in the treatment of severe forms of pain. To improve present therapies, a long-acting single-dose gel injection would be beneficial. The present study investigated the use of three different polymers as additives in injectable poloxamer gel in controlling the drug release. The release of lidocaine⋅HCl and ibuprofen⋅Na from 25% poloxamer (PO) gel and poloxamer gel with hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (CMC), or dextran (DE) was studied in vitro. Cellulose additives significantly prolonged ibuprofen release, whereas additives were found to have a slight release-increasing effect on lidocaine as compared with the PO gel. The structural differences of the gels, more than the macroviscosity, seem to regulate the release of drugs. The drug permeation-prolonging effect of the respective gels, along with the control solutions, was evaluated in vitro using porcine dura mater membrane. The compact gel depot acted as the rate-limiting step, and significantly prolonged the dural permeation of both drugs in comparison with control solutions. The difference in the drug release and permeation-reducing effects of the gels demonstrated the possibility for interactions between dural membrane and the gel. The findings are promising for further experimental in vivo animal testing of these injectable poloxamer-based gels.

Continuous supraclavicular brachial plexus blocks are useful for long surgical operations on the shoulder and upper extremily. Their usefulness can be increased with continuous infusions of local anesthetics through the same catheter for postoperative analgesia. Our technique includes the use of a commercial set (Contiplex; B. Braun Medical Inc, Melsungen, Germany and Bethlehem, PA). For shoulder surgery the most superficial trunk of the plexus is identified by using a nerve stimulator with a low current (0.2–0.3 mA) and motor response distal to the shoulder. The initial surgical anesthetic dose of 1% mepivacaine, 0.75% bupivacaine or 0.75% ropivacaine, with 5 μg/mL epinephrine, is injected. Then the catheter is threaded as far as it can be advanced without obstruction (usually less than 1 cm past the tip of the cannula). To have a functional catheter for 24 to 48 hours, it must be tightly fixed to the skin with tape or sutures. For postoperative analgesia, an infusion of either 0.25% bupivacaine or 0.2% ropivacaine solution can be used. Complications from catheter use are rare but occasional intraarterial catheterizations and epidural blocks have been observed. A phrenic nerve block will always accompany a successful supraclavicular brachial plexus block and hemidiaphragmatic dysfunction can occur as long as the infusion continues.

Unbound, rather than total, plasma concentrations may be related to the anaesthetic action of propofol. Therefore, we measured plasma concentrations of propofol and recorded Nb wave latencies of auditory evoked potentials (AEP) during continuous infusion of propofol in 15 patients undergoing coronary artery bypass grafting (CABG) surgery. After induction of anaesthesia with fentanyl, propofol was infused continuously at a rate of 10 mg kg-1 h-1 for 20 min, and then the rate was reduced to 3 mg kg-1 h-1. Administration of heparin before cardiopulmonary bypass (CPB) did not affect total or unbound propofol concentration. Initiation of CPB decreased mean total propofol concentration from 2.6 to 1.7 micrograms ml-1 (P0.01). Simultaneously, mean unbound propofol concentration remained at 0.06 micrograms ml-1 because of a slight increase in the mean free fraction of plasma propofol (from 2.3 to 3.5%; P0.05). During hypothermic CPB, mean total propofol concentration increased to concentrations measured before bypass (to 2.1 micrograms ml-1; P0.05 vs value before CPB) and the mean unbound propofol concentration was at its highest (0.07 microgram ml-1; P0.05 vs value before heparin). After CPB and administration of protamine, the mean total propofol concentration remained lowered (1.7 micrograms ml-1; P0.05 vs value before heparin) and the mean unbound propofol concentration returned to the level measured before heparin (P0.001 vs value during hypothermia). The latency of the Nb wave from recordings of AEP increased after induction of anaesthesia, reached its maximum during hypothermia and was prolonged during the subsequent phases of the study. The latency of the Nb wave did not correlate with total or unbound propofol concentration. We conclude that the changes in total and unbound concentrations of plasma propofol were not parallel in patients undergoing CABG. During CPB or at any other time during the CABG procedure, the unbound propofol concentration did not decrease and Nb wave latency was prolonged compared with baseline values measured after induction of anaesthesia before the start of CPB.

Venous air embolism (VAE) is a recognized complication of surgery performed with the patient in the sitting position, but it occurs also during other operations. We report two cases of VAE, associated with a notable decrease in dynamic lung compliance, detected by side-stream spirometry. Based on these cases, an experiment with 10 pigs was designed to evaluate the usefulness of side-stream spirometry in the diagnosis of VAE. Three doses of air (0.5, 1.0 and 2.0 ml kg-1) were injected via the proximal part of a 5- French gauge pulmonary artery catheter. Only the largest dose was followed by haemodynamic deterioration. Significant increases in end-tidal oxygen content and decreases in dynamic lung compliance were detected with all doses of air together with conventional signs of VAE, that is increases in pulmonary artery pressures and arterial carbon dioxide tensions, and decreases in end-tidal concentration of carbon dioxide. We conclude that continuous monitoring of end-tidal oxygen concentration and side-stream spirometry offers valuable supplements to other monitoring techniques in the detection of VAE.

Propofol is sequestered in extracorporeal circuits, but the factors responsible for the phenomenon are mostly unknown. We have compared two extracorporeal circuits (oxygenators, reservoirs and tubings) coated with heparin with two corresponding uncoated circuits for their capacity to sequester propofol in vitro. Three experiments were conducted with each circuit. The circuit was primed with a mixture of Ringer's acetate solution and whole blood, and the study conditions (pump flow, temperature, pH) were standardized. Propofol was added to the solution to achieve a concentration of 2 micrograms ml-1. These studies were followed with concentrations of 10- and 100-fold to assess possible saturation of propofol binding. Serial samples were obtained from the circulating solution for measurement of propofol concentration. Propofol concentrations decreased to 22-32% of the initial predicted concentration of 2 micrograms ml-1 in the circuits (no significant difference between circuits). With greater concentrations, the circuits did not become saturated with propofol, even with the highest predicted concentration of 200 micrograms ml-1. We conclude that propofol was sequestered in extracorporeal circuits in vitro, irrespective of coating the circuit with heparin.

This statement is based on four prospective and one retrospective studies on out-of-hospital cardiac arrests conducted according to the Utstein style, and on the summary that brings the five studies together [1– 6]. The prospective studies were conducted in Helsinki (population approximately 525000 inhabitants) in the Helsinki City emergency medical services (EMS) system and at the Department of Anaesthesia, University of Helsinki, during 1994–1996; the retrospective study was for the period 1985–1994. Altogether, the total number of cardiac arrest patients was 888. One of the main objectives was to evaluate the suitability of the Utstein style recommendations [7] for data collection, and to find possibilities for improvement. The recommended changes to the Utstein style are reported in this statement.

We studied 40 patients, 18-60 yr, undergoing orthopaedic surgery of the lower limb under spinal anaesthesia. A midline lumbar puncture was performed in the L3-4 interspace using a 27-gauge needle with the patient in the lateral horizontal position. Plain bupivacaine 3 ml at room temperature was injected. The cephalad level of analgesia was assessed by pinprick 60 min after injection of local anaesthetic, at the end of surgery and again after the patient was moved into bed. All patients had a segmental level of the block of L1-T5 at the beginning of the study. The upper half of the patient's body was then tilted to a 30 degrees head-up position. Segmental spread was subsequently assessed by pinprick at 5-min intervals for 30 min. In six of the 40 patients (15%), increased cephalad spread of spinal analgesia occurred. The mean time from induction of spinal anaesthesia was shorter in these six patients (mean 92 min, range 80-115 min) than in the patients whose block did not change or was decreasing during the 30-min test (mean 119 min, range 83-210 min) (P0.05). We conclude that the patient should remain in the supine horizontal position until recovery from the spinal block.

Study objective Our objective is to investigate to what extent amiodarone is sequestered by intravenously administered lipid emulsion in plasma of pigs and whether the lipid emulsion inhibits amiodarone-induced hypotension. Methods Twenty anesthetized pigs received randomly 1.5 mL/kg bolus injection of olive/soybean oil–based 20% lipid emulsion (lipid group, n=10) or Ringer's acetate solution (control group, n=10) in 1 minute, followed by a continuous infusion of either solution for 30 minutes at 0.25 mL/kg per minute. Simultaneously with these continuous infusions, amiodarone hydrochloride was infused for 20 minutes at 1 mg/kg per minute in both groups. Plasma amiodarone concentration and mean arterial blood pressure were evaluated at predetermined intervals. Results Plasma amiodarone concentration in the lipid group increased more steeply during the amiodarone infusion than in the control group, at 20 minutes being a median 96.8 mg/L (interquartile range [IQR] 85.4, 102.0 mg/L) in the lipid group and median 21.5 mg/L (IQR 18.9, 22.3 mg/L) in the control group (difference 75.3 mg/L; 95% confidence interval [CI] 65.3 to 85.3 mg/L). After the separation of lipids from plasma by differential centrifugation, less amiodarone was contained in the lipid-poor aqueous fraction. At 20 minutes, the median was 13.3 mg/L (IQR 12.0, 13.7 mg/L), and the difference compared with the total plasma amiodarone concentration was −83.6 mg/L (95% CI −93.3 to −73.8 mg/L). In the lipid group, mean arterial blood pressure was not altered during the continuous amiodarone infusion. In the control group, mean arterial blood pressure decreased from baseline at 11 minutes, and the median was 52 mm Hg (IQR 51, 80 mm Hg) and the difference from baseline was 26 mm Hg (95% CI 9 to 43 mm Hg). Mean arterial blood pressure at 21 minutes also remained below the baseline, and the median was 57 mm Hg (IQR 50, 68 mm Hg) and the difference from baseline was 21 mm Hg (95% CI 9 to 33 mm Hg). Conclusion Amiodarone was sequestered to a great extent by the intravenously administered lipids in plasma, which completely prevented the decrease in arterial blood pressure caused by amiodarone infusion. Further studies are needed to evaluate the clinical usefulness of intravenous lipid emulsion as an antidote in amiodarone overdoses.

SUMMARY The differential blocking effect of bupivacaine and 2-chloroprocaine was studied on isolated rabbit cervical sympathetic trunks (B and C fibres) and phrenic nerves (A fibres). The B fibres (myelinated, preganglionic) were more sensitive than C fibres (unmyelinated, postganglionic) to nerve block by bupivacaine and 2-chloroprocaine, as assessed by changes in action potential amplitude and latency. The blocking action of both bupivacaine and 2-chloroprocaine caused a decrease in amplitude in the B fibres approximately twice as great as that produced in the C fibres. In similar experimental conditions, the fastest conducting A fibres (myelinated, motor) were least affected. Bupivacaine 200 μmol litre −1 completely blocked all B fibres in 7 min and C fibres in 10 min. The average action potential amplitude of A fibres at that time was 78%. 2-Chloroprocaine 300 (imol litre −1 completely blocked B fibres in 4 min and C fibres in 15 min. At 15 min the average action potential amplitude of the A fibres was still approximately 35%. Although these two local anaesthetics differ structurally and physico-chemically, the rates of block of the different fibres were in the same order in vitro .

The effects were studied, in eight healthy volunteers, of premedication with diazepam 0.14 mg kg-1 by mouth or hyoscine 6 micrograms kg-1 + morphine 0.2 mg kg-1 i.m., or no premedication, on toxic symptoms and plasma concentrations after rapid i.v. injection of lignocaine 1 mg kg-1. The alpha 1-acid glycoprotein (AAG) and albumin plasma protein fractions were assessed. A variety of mild central nervous system (CNS) symptoms were experienced after the bolus of lignocaine. However, there was no correlation between premedication and degree of severity or number of CNS symptoms. The highest single arterial plasma concentration of lignocaine was 11.0 micrograms ml-1, 1 min after injection. There was no correlation between plasma concentration of lignocaine and occurrence of CNS symptoms. Furthermore, there was no correlation between AAG or albumin plasma concentrations and lignocaine plasma concentrations.