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Arterial blood gas (ABG) analysis is the traditional method for measuring the partial pressure of carbon dioxide. In mechanically ventilated patients a continuous noninvasive monitoring of carbon dioxide would obviously be attractive. In the current study, we present a novel formula for noninvasive estimation of arterial carbon dioxide. Eighty-one datasets were collected from 19 anesthetized and mechanically ventilated pigs. Eleven animals were mechanically ventilated without interventions. In the remaining eight pigs the partial pressure of carbon dioxide was manipulated. The new formula (Formula 1) is PaCO2 = PETCO2 + k(PETO2 &minus, PaO2) where PaO2 was calculated from the oxygen saturation. We tested the agreements of this novel formula and compared it to a traditional method using the baseline PaCO2 &minus, ETCO2 gap added to subsequently measured, end-tidal carbon dioxide levels (Formula 2). The mean difference between PaCO2 and calculated carbon dioxide (Formula 1) was 0.16 kPa (&plusmn, SE 1.17). The mean difference between PaCO2 and carbon dioxide with Formula 2 was 0.66 kPa (&plusmn, SE 0.18). With a mixed linear model excluding cases with cardiorespiratory collapse, there was a significant difference between formulae (p &lt, 0.001), as well as significant interaction between formulae and time (p &lt, 0.001). In this preliminary animal study, this novel formula appears to have a reasonable agreement with PaCO2 values measured with ABG analysis, but needs further validation in human patients.

Background Although the incidence of severe local anaesthetic systemic toxicity (LAST) has been declining, the risk of LAST still remains. There are no national treatment guidelines for LAST in Finland. We performed a national survey of the occurrence of LAST and its treatment in 2011–2013. Methods A structured electronic questionnaire was sent to the anaesthesia department chiefs of all Finnish public hospitals (n = 45) in spring 2014. We collected information about the occurrence and outcome of LASTs and existence of treatment protocols. Results The questionnaire response rate was 100% covering approximately 95% of all regional anaesthesias managed by anaesthesiologists in Finnish hospitals. The total number of regional anaesthesias, excluding spinal anaesthesia, performed by anaesthesiologists was approximately 211,700 during the survey period. Fifteen cases of LAST were reported (0.7 : 10,000); all patients recovered without negative sequelae. Fourteen patients, in five of whom ultrasound guidance had been applied, developed central nervous system toxicity symptoms and only one cardiac symptoms. Lipid emulsion was given to this latter patient, and to four of the other 14. The relative risk (95% confidence intervals) for occurrence of LAST in non-academic hospital vs. university hospitals was 3.3 (1.0–10.3; P = 0.04). Treatment protocols for LAST included lipid emulsion in 47% of the departments. Conclusions The incidence of LAST in Finland is very low. Several departments have adopted lipid emulsion treatment for LAST despite lack of national recommendations and knowledge of the possible mechanism of action.

Background and aims Bone marrow aspiration and/or biopsy (BMAB), performed under local anaesthesia in adults, is a common and often painful procedure. Anxiety is known to intensify pain during the procedure. Nitrous oxide (N2O), known for its sedative and analgesic benefit in various short medical procedures and labour pain, could be advantageous also for pain relief during bone marrow examination. N2O acts rapidly and is eliminated in a couple of minutes once the inhalation is stopped, and occasional side effects (e.g. dizziness and nausea) are mild. The aim of this study was to compare the analgesic effects of inhaled 50% mixture of nitrous oxide and oxygen to 50% oxygen during bone marrow examination. Methods In this randomized, controlled, patient and observer blinded study patients received either 50% mixture of nitrous oxide and oxygen or 50% mixture of oxygen in air during bone marrow examination, in addition to local analgesia. Both patient groups comprised 35 adult patients. Pre-procedural anxiety and procedural pain were rated on the Numeral Rating Scale (NRS 0‒10). Cognitive function was measured before and 30 min after the procedure. Possible side effects were recorded. A telephone interview was performed 24 h later. Results There were no statistically significant differences in pain scores of the procedural steps (median NRS ranging 3.0‒4.0) between the study groups. High pain scores of 8‒10 comprised 0% vs. 8.6% of the scores during infiltration, 2.9% vs. 5.7% during puncture, 11.4% vs. 14.3% during aspiration and 2.9% vs. 2.9% during biopsy in N2O and 50% O2 groups, respectively (NS). Pre-procedural anxiety (median NRS 3.5 in both groups), measured in the outpatient clinic just prior to procedure, correlated with pain intensity during bone marrow aspiration (P = 0.045). There were no significant differences between side effects. During the BMAB four patients (3 in N2O group, 1 in 50% O2 group) reported dizziness and one patient in the N2O group reported nausea. Gas inhalation did not affect the cognitive function of the participants. In both groups the majority (>80%) of the patients was satisfied with the inhalation technique. During the 24 h interview, most of the participants were pain free and they did not report any serious adverse effects. Conclusions In spite of similar moderate to strong procedural pain in both groups and no benefit of N2O, most patients were satisfied with the inhalational techniques. We assume that the bedside presence of an anaesthesiologist and the distraction caused by the inhalational arrangements introduced positive context-sensitive therapeutic effect independent of the gas used. Pre-procedural anxiety predicted pain associated with bone marrow aspiration. Implications Inhaled 50% nitrous oxide was not an effective analgesic during bone marrow examination in our unselected outpatient population. Further studies should concentrate on its use with patients predicted to be at increased risk of suffering intense pain during the procedure, such as very anxious patients or those who have a painful history of previous bone marrow examinations.

Intravenous lipid emulsion has been suggested as treatment for local anaesthetic toxicity, but the exact mechanism of action is still uncertain. Controlled studies on the effect of lipid emulsion on toxic doses of local anaesthetics have not been performed in man. In randomized, subject-blinded and two-phase cross-over fashion, eight healthy volunteers were given a 1.5 ml/kg bolus of 20% Intralipid(®) (200 mg/ml) or Ringer's acetate solution intravenously, followed by a rapid injection of lidocaine 1.0 mg/kg. Then, the same solution as in the bolus was infused at a rate of 0.25 ml/kg/min. for 30 min. Electroencephalography (EEG) was recorded, and 5 min. after lidocaine injection, the volunteers were asked to report subjective symptoms. Total and un-entrapped lidocaine plasma concentrations were measured from venous blood samples. EEG band power changes (delta, alpha and beta) after the lidocaine bolus were similar during lipid and during Ringer infusion. There were no differences between infusions in the subjective symptoms of central nervous system toxicity. Lidocaine was only minimally entrapped in the plasma by lipid emulsion, but the mean un-entrapped lidocaine area under concentration-time curve from 0 to 30 min. was clearly smaller during lipid than Ringer infusion (16.4 versus 21.3 mg × min/l, p = 0.044). Intravenous lipid emulsion did not influence subjective toxicity symptoms nor affect the EEG changes caused by lidocaine.

Recent investigations have proved the usefulness of spectroscopy in endoscopic examinations of the gastrointestinal tract in human medicine. However, current commercially available spectroscopy methods are relatively expensive. Near infrared (NIR) diffuse reflectance spectroscopy is a more cost-effective method. To assess its applicability for gastrointestinal endoscopy in veterinary medicine, in a pilot study we tested its feasibility for the differentiation of parts of the healthy gastrointestinal wall of pigs. Both white light standard endoscopy and NIR endoscopy were performed on the corpus, antrum and duodenum of seven clinically healthy pigs. General and gastrointestinal health was assessed by history, clinical examination and post-mortem examination. The spectral values of NIR endoscopy were obtained at intervals of about 0.3 nm in the range of 195–1118 nm. The method for the analysis of endoscopically taken NIR spectra consisted of pre-processing, feature extraction and classification. After smoothing, down-sampling and feature computing, spectral data were analysed using the principal component analysis (PCA) and partial least squares (PLS) techniques. The best algorithm performance was achieved using the spectra-PCA-SVC, giving a classification rate of 0.76. Further research is needed to assess the applicability of NIR endoscopy in other species and in animals showing gastrointestinal pathology. To improve the classification rate, probe calibration must be optimised and cleanness of the gastrointestinal tract ensured.

Background and purpose Local infiltration anaesthesia is frequently painful due to low pH of the used anaesthetics, such as lidocaine. Usually pH of the solution is near 4.0, which causes tissue irritation and excitation of the pain mediating nerve endings. Warming and buffering the local anaesthetic solution have been shown to reduce the patient’s experience of pain and unpleasantness during infiltration. Buffering reduces the dissociation of the local anaesthetic molecule and may enhance the anaesthetic’s entrance into nerve cells. In this randomized placebo-controlled trial warmed and buffered lidocaine with adrenaline was compared to room temperature unbuffered lidocaine with adrenaline infiltrated before bone marrow aspiration and/or biopsy (BMAB). The aim was to find out to what extent warming and buffering would diminish pain during infiltration and whether this would be reflected in less pain also during subsequent steps of the BMAB procedure. Methods One hundred patients scheduled to undergo BMAB were interviewed regarding subjective experiences from previous medical procedures, current chronic and temporary medications, and their present state of anxiety before the BMAB procedure. They received local anaesthetic infiltration of lidocaine prior to BMAB. The solution used was either warmed lidocaine 20 mg/ml with adrenaline buffered with sodium bicarbonate 75 mg/ml (warmed and buffered group, 50 patients, pH approximately 7.3, 32°C) or unbuffered lidocaine 20 mg/ml with adrenaline mixed with NaCl 0.9% solution (control group, 50 patients, pH approximately 3.7, room temperature). The lidocaine concentration was similar in both groups. The bone marrow sampling needle was inserted 2 min after local anaesthetic infiltration. The grade of preprocedural anxiety, and pain sensations during the BMAB, both rated on NRS (numeral rating scale, 0–10) were compared between the groups. Results In comparison with the use of an unbuffered solution at room temperature warmed and buffered lidocaine with adrenaline caused less pain during infiltration (median NRS 4.0 vs. 2.0, P < 0.002) but it did not make performing the other phases of BMAB any less painful. As expected, painful experiences from previous medical, other than BMAB, or dental procedures and anxiety were associated with local anaesthetic infiltration pain during BMAB. Patients’ own pain or anxiolytic medication did not lessen pain during BMAB. Conclusions By warming and buffering the lidocaine solution containing adrenaline it is possible to make the pain during infiltration less intense. Unfortunately, such benefit was not detected during the following steps of BMAB, initiated 2 min later. Preprocedural anxiety made procedural pain more intense including that of the local anaesthetic infiltration. Implications Warming and buffering the local anaesthetic prior to its administration is an effective and simple way of diminishing pain during infiltration. This benefit seems to be underutilized in the BMAB procedure. However, warming and buffering are not sufficient enough to diminish pain during bone marrow sampling and thus additional pain alleviating methods should be used, particularly in patients showing preprocedural anxiety.

Background Expertise in neonatal resuscitation is essential for personnel involved in the care of newborns. In this observational cohort study the skills of 52 midwives in a simulated scenario were assessed. Methods A total of 52 midwives in a low-risk unit and five specialist nurses in a high-risk unit were tested to establish their competence in newborn resuscitation. The 52 midwives were divided into groups 1 (n = 39; no pretest training) and 2 (n = 13; 1 day training prior to study). The video-recorded test scenario was a newborn with asphyxia. Thirty items were graded by a neonatologist and nursing team in real time. Using the Angoff method, a pass score was 18.71 for skills that were graded 0 or 1. Results The average score of specialist nurses was 26 (range, 23–29). A total of 49% of midwives in group 1 and 92% in group 2 passed the test. The average score was 17.7 (range, 9–25) in group 1 and 21.9 (range, 17–27) in group 2. A total of 27% and 77% of midwives in groups 1 and 2, respectively, carried out ventilation at a frequency as per the algorithm. Mask leakage was higher in group 1 (44%) versus group 2 (23%). Five and three midwives in groups 1 and 2, respectively, overexpanded the lungs. Conclusion Many midwives had imperfect resuscitation skills. A 1 day course improved such skills. The standard scenario is an objective and useful performance marker in assessing and documenting improvements in competence in delivery room resuscitation.

Background Articaine and chloroprocaine have recently gained interest as short-acting spinal anaesthetics. Based on previous work comparing articaine 60 mg with chloroprocaine 40 mg, we hypothesised that articaine 40 mg and chloroprocaine 40 mg would produce similar spinal anaesthesa regarding block onset, maximal spread, and recovery. Methods In this randomised, double-blind study, adult patients (18–70 years, American Society of Anaesthesiologists physical status I-III, BMI

Background Bone marrow aspiration and/or biopsy (BMAB) is often an unpleasant and painful procedure in spite of local anaesthetic infiltration. This randomized placebo-controlled trial compared the pain relieving effect of sublingual fentanyl and placebo during BMAB. Methods One hundred sixty patients were randomized to receive either sublingual fentanyl 200 μg, 100 μg (patients ≥ 70 years old, weight ≤ 50 kg or in poor health) or placebo before BMAB. The grade of anxiety before the procedure and the grade of pain during local anaesthetic infiltration, aspiration, biopsy and immediately after the BMAB were assessed using the Numeral Rating Scale (0–10). Possible side effects of the study drugs were recorded. Results Sublingual fentanyl proved inadequate in relieving pain during BMAB as no significant differences in the pain scores of the fentanyl and placebo patients were observed. However, fentanyl caused significantly more dizziness than placebo. Conclusions The results suggest that sublingual fentanyl in a dose of 200 μg (100 μg in infirm patients) is not a feasible preventive analgesic during BMAB. Pain scores were similar and side effects more frequent in the fentanyl group than in the placebo group.

In order to avoid the risks of sideeffects of epidural local anesthetics and opioids, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) epidurally would be an interesting option of analgesic therapy. The fairly short duration of action of spinally administered NSAIDs, e.g., ibuprofen, may be prolonged by using controlled release poloxamer gel formulation. Using a microdialysis technique we studied the epidural and intrathecal pharmacokinetics of ibuprofen after its epidural administration as a poloxamer 407 formulation or a solution formulation. In addition, plasma ibuprofen concentrations were analyzed from central venous blood samples. Ibuprofen concentrations in the epidural space were significantly higher and longer lasting after the epidural gel injection compared with the epidural solution injection. The epidural AUC of ibuprofen was over threefold greater after epidural ibuprofen gel injection compared with the ibuprofen solution injection (p

Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid® ( n = 7) with Ringer’s acetate ( n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer’s acetate administration ( p < 0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid ( p < 0.05) but unaffected by Ringer’s acetate. The mean (standard deviation) area under the concentration–time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg·min/L) than after Ringer’s acetate (88.1 (7.1) mg·min/L) ( p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg·min/L) was 8% lower than that of total bupivacaine ( p < 0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function.

BACKGROUND The reported successful use of IV lipid emulsions in local anesthetic intoxications is thought to be due to lipid sequestration of local anesthetics. However, controlled efficacy studies were lacking, and other mechanisms of action have also been suggested. We investigated the effect of lipid infusion on plasma concentrations and cardiovascular effects of 2 local anesthetics differing in lipophilicity, bupivacaine, and mepivacaine. METHODS Bupivacaine (n = 20) or mepivacaine (n = 20) was infused into a central vein of anesthetized (isoflurane 1%, Fio(2) 0.21) pigs until mean arterial blood pressure decreased to 50% from baseline. Isoflurane was discontinued and Fio(2) was increased to 1.0. Ten pigs in each local anesthetic group were treated with 20% lipid emulsion (ClinOleic®), and 10 pigs with Ringer's solution: 1.5 mL/kg in 1 minute followed by an infusion of 0.25 mL · kg(-1) · min(-1) for 29 minutes. Five additional pigs were infused bupivacaine and Intralipid®. Total and nonlipid-bound local anesthetic concentrations were determined from repeated blood samples. RESULTS There were no overall differences in total or nonlipid-bound plasma local anesthetic concentrations between the lipid and Ringer's groups. However, plasma median total bupivacaine concentration was 21% and 23% higher at 20 and 30 minutes, respectively, in the lipid group (P = 0.016 without Holm-Bonferroni correction). There was also no overall difference between lipid and Ringer's groups in the rate of recovery of hemodynamic and electrocardiographic variables. Median mean arterial blood pressure in the lipid group with bupivacaine intoxication was 16 mm Hg and 15 mm Hg higher than in the corresponding Ringer's group at 10 and 15 minutes, respectively (P = 0.016 and P = 0.021, respectively, without Holm-Bonferroni correction). Intralipid® also caused no difference between total plasma and nonlipid-bound concentrations of bupivacaine with no apparent enhancement of recovery. CONCLUSIONS Lipid emulsion neither had any measurable effect on the disposition of the studied local anesthetics in plasma, nor did it improve the rate of recovery from intoxication by either local anesthetic as measured by hemodynamic variables.

Intravenous lipid emulsion is the recommended treatment for severe local anaesthetic intoxication. Lipid emulsion may entrap lipid soluble drugs by functioning as a 'lipid sink', but its effect on bupivacaine pharmacokinetics remains unknown. In this randomised, double-blind, crossover study, eight healthy male volunteers were infused bupivacaine 0.5mg.kg(-1) intravenously over 20 min, followed by an infusion of either intravenous lipid emulsion or Hartmann's solution for 30 min. At 20 and 30 min after the start of the infusion, the total plasma bupivacaine concentration was lower while receiving lipid emulsion than Hartmann's solution (mean difference 111 (95% CI 55-167) μg.l(-1) and 75 (95% CI 26-124 μg.l(-1) at 20 and 30 min, respectively; p

In recent years, several older (first intrathecal use in the 1950s, 1960s, and 1970s) local anesthetics have been investigated as spinal anesthetics in ambulatory surgery because these drugs are claimed to cause less transient neurologic symptoms (TNS) than lidocaine which was the main spinal anesthetic for surgery of short-duration for decades. The review covers the current literature.Several recent reports have dealt with the short-acting chloroprocaine and articaine and the intermediate-duration-acting prilocaine. Mepivacaine, another intermediate-acting drug, was applied in one trial only. Various dosages of these drugs either alone or with a small dose of fentanyl were compared with each other, with lidocaine, or with the currently most commonly used low-dose bupivacaine technique. The recovery from both motor and sensory block was usually reasonably fast. However, occasionally recovery after mepivacaine and prilocaine was prolonged which fits ill in a fast-flow ambulatory setting. TNS cases were very rarely reported.The newest results corroborate (at least for chloroprocaine, articaine, and prilocaine) previous data that these drugs provide reliable and mostly well tolerated spinal blocks associated with an apparently smaller risk for postanesthesic TNS as compared with lidocaine. Further studies are warranted regarding broader indications, possible usefulness of adjuvants, and for the exploration of the side-effect profiles in detail. To what extent the observed revival of these older, rather well characterized local anesthetics leads to a wider use of spinal anesthesia in the ambulatory setting remains to be seen. This is also dependent on various organizational and local traditional factors.

Intravenous lipid emulsion has been used in the resuscitative treatment of intoxications caused by local anaesthetics and tricyclic antidepressants with seemingly beneficial results. We studied the effect of intravenous lipid emulsion on the plasma concentration of amitriptyline and haemodynamic recovery in a pig model of amitriptyline intoxication. Twenty pigs were anaesthetized (1% isoflurane in 21% O(2)) and given amitriptyline 15 mg/kg intravenously for 15 min. In random fashion immediately thereafter, either 20% lipid emulsion (ClinOleic(®), Lipid group) or Ringer's acetate (Control group) was infused for 30 min.; first 1.5 ml/kg for 1 min., followed by 0.25 ml/kg/min. for 29 min. The amitriptyline concentration in total and lipid-poor plasma and haemodynamic parameters were measured until 30 min. after the infusions. Lipid infusion prevented the decrease in plasma total amitriptyline concentration, resulting in a 90% higher (p < 0.001) total concentration and significantly (p = 0.014) lower free fraction of plasma amitriptyline in the Lipid group (1.1%) compared with the Control group (3.0%) at 30 min. Haemodynamic recovery from the intoxication as measured by heart rate, arterial pressure or cardiac output was similar in both groups. However, five pigs in the Lipid group and two pigs in the Control group died. In conclusion, a marked entrapment of amitriptyline by intravenous lipid emulsion was observed but this did not improve the pigs' haemodynamic recovery from severe amitriptyline intoxication. Care should be exercised in the antidotal use of lipid emulsion until controlled human studies indicate its efficacy and safety.

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.

Background: Chloroprocaine and articaine have recently gained interest as short-acting spinal anaesthetics. They have not, however, previously been compared in an ambulatory surgery setting. Methods: In this double-blind, randomised, controlled trial, adult patients (≤65 years, ASA I–II, body mass index

Background and objectives: Difficulties in communication and lack of suitable pain scales may lead to undertreatment of pain in cognitively impaired patients. We performed a study in this type of patients and evaluated the usefulness of four simple pain scales. Patients and methods: We studied 41 hospitalized elderly (76–95 years) who suffered from pain with an acute component. Cognitive function was assessed with the mini-mental state examination (MMSE) and the degree of depression was assessed on the geriatric depression scale (GDS). Pain intensity was assessed at rest and after a pain-provoking movement three times at 2-week intervals by repeating the test at a 10-min interval at each test session. The pain scales were the 50 cm red wedge scale (RWS), the seven-point faces pain scale (FPS), the 10 cm visual analogue scale (VAS) and the five-point verbal rating scale (VRS). Results: In group MMSE≥24, patients were able to use all four scales rather successfully. In the other groups (MMSE 17–23, 11–16 and ≤10), only the use of VRS was successful to a reasonable degree (64–85% on average). GDS scores did not correlate with the pain scores, with the exception of pain scores on FPS during movement (P

Methoxyflurane and tetracyclines may cause dose-related renal dysfunction. In the present study rats were treated with oxytetracycline (37.5 and 75 mg/kg/day) or tetracycline (75 mg/kg/day) intraperitoneally for four days and one methoxyflurane anaesthesia (1 % for 45 minutes) was given on the second day. The combined treatment as well as methoxyflurane anaesthesia alone, caused polyuria, elevated urinary fluoride excretion, increased serum uric acid concentration and SGPT activity. The histological examination showed shrinkage of glomeruli and tubular protein deposits in the kidneys and marked fat infiltration in the liver of rats treated with the antibiotics and methoxyflurane, while the anaesthetic seemed to cause only slight fatty changes in the liver. A probable renal tubular lesion caused by methoxyflurane, or its metabolites, was indicated by the polyuric effect, the lack of response to injected vasopressin and the uric acid retention while the tetracyclines probably added to the toxic effect mainly through their anti-anabolic action. Oxytetracycline, in combination with one halothanc anaesthesia, did not seem to cause hepatotoxicity in the rats.

Several drugs modify the lethal action of trifluoroethanol (TFE) and trifluoroacetaldehyde hydrate (TFA1H). The toxic effect of these metabolites of halothane may be due to the reactions of trifluoroacetaldehyde (TFA1), since the toxicity of TFE was reduced by the administration of ethanol (500 mg/kg × 2, intraperitoneally) or 4-iodo-pyrazole (50 mg/kg × 2, intraperitoneally), an inhibitor of alcohol dehydrogenase. Furthermore, allopurinol (20 mg/kg × 2, intraperitoneally), which as an inhibitor of xanthine oxidase may decrease the further oxidation of TFA1, increased the toxicity of TFE and TFA1H but not that of trifluoroacetic acid (TFAA). Isoniazid (50 mg/kg × 2, intraperitoneally), a carbonyl reagent, effectively reduced the toxicity of TFE and TFA1H, while cysteine (500 mg/kg × 2, intraperitoneally) showed some protection against the TFE toxicity. Cysteine, in vitro, also prevented the inhibitory action of TFA1H and TFAA on the creatine phosphokinase (CPK) activity. TFE did not inhibit this SH-enzyme in vitro. Thus the formation of a thiol-binding aldehyde may be essential for the metabolic blocking effect and toxicity of TFE and TFA1H.

The aim of the study was to compare the effectiveness of teaching of general anaesthesia induction to medical students using either full-scale simulation or traditional supervised teaching with patients in the operating theatre.Forty-six fourth year students attending their course in anaesthesiology were enrolled. The students were randomly assigned to two groups. The simulation group received training in the simulator. The traditional training group was supervised by a senior consultant anaesthetist. After the training sessions all students were tested in the simulator setting. The test was assessed using a 40-item evaluation list.Thirty-three per cent of students in the traditional group and 87% of the students in the simulation group passed the test. Statistically significant differences were: request of glycopyrrolate (P0.001), Sp(O2) monitoring (P0.001), used gloves when placing an intravenous cannula (P = 0.012), intubation attempt within 30 s (P0.04), anaesthesia gas set at MAC at least 1 (P0.04), instructed anaesthetic nurse to keep Sp(O2) at least 95% (P0.05), keep MAP at least 60 mmHg (P0.05), keep heart rate more than 50 beats per minute (P0.002), keep end-tidal p(CO2) 4-5.5 kPa (P0.002).The simulation group performed better in 25% of the tasks and similarly in the others compared with the traditional teaching group. With the same time and amount of teaching personnel we trained five or six students in the simulator compared with one student in the operating theatre. Further research will reveal whether these promising results with simulation may be applied more generally in anaesthesiology teaching to medical students.

Background: In elderly patients, opioids may cause prominent postoperative sedation and respiratory depression. We evaluated the influence of age on the effects of opioids and plasma concentrations of fentanyl and oxycodone in cardiac surgery patients. Methods: Thirty (≥75 years, gender M9/F21) and 20 (≤60 years, gender M20/F0) patients scheduled to undergo cardiac surgery. A standard anesthesia with fentanyl as an opioid was used. Fentanyl plasma concentrations were measured at the end of surgery and 2 h later. After tracheal extubation, when the pain intensity was at least moderate, blood samples for fentanyl and oxycodone plasma concentration measurements were taken. Thereafter, oxycodone hydrochloride 0.05 mg/kg i.v. was administered. After 15 and 45 min, pain intensity, sedation and oxycodone plasma concentration were determined. This test protocol was repeated twice. Results: The elderly had a higher plasma concentration of fentanyl at the end of surgery than younger patients (5.7±2.2 vs. 3.8±1.2 ng/ml, P=0.001). The plasma concentrations of oxycodone were comparable between the groups. The interval between the second and the third oxycodone dose was longer in the elderly patients (P=0.036). Pain intensity on the verbal rating scale was lower at the 45-min assessment point after all three oxycodone test doses (P=0.008) and sedation scores were significantly higher after the third dose in the elderly patients (P=0.035). Conclusions: In elderly patients, the plasma concentration of fentanyl was higher but plasma levels of oxycodone were at a similar level compared with middle-aged patients. However, the elderly patients had less pain and were more sedated after doses of oxycodone.

Background: Post-operatively, elderly patients with impaired vision and cognitive dysfunction may experience difficulties understanding standard pain assessment tools such as the 10-cm Visual Analogue Scale (VAS) and the Verbal Rating Scale (VRS). Thus, there is a need to identify more feasible post-operative pain assessments for elderly patients. With this goal in mind, we compared the VAS and VRS with two more expressive tools: the 50-cm Red Wedge Scale (RWS) and the Facial Pain Scale (FPS). Methods: Cardiac surgery patients (73 ± 5 years, mean ± SD) were allocated to an RWS (n=80) or an FPS (n=80) group. Pain was assessed at rest and after movement during the first 4 days after tracheal extubation. The RWS or FPS assessments were repeated after 10 min. All patients completed the VRS and VAS. Results: The rates of successful pain measurement on study day 1 were: VRS 86%, VAS 62%, RWS 78%, and FPS 60%. Pain measurements with the RWS correlated with the VAS (r=0.758, P

The surgical site for the creation of an arteriovenous fistula at the lateral aspect of the distal forearm may be faster and more effectively blocked with the infraclavicular coracoid approach than with the axillary approach for brachial plexus block.Sixty uremic patients scheduled for the creation of an arteriovenous fistula at the forearm were randomized to receive a single-injection brachial plexus block with 35 to 50 mL mepivacaine 0.95% with epinephrine using the infraclavicular coracoid approach (IC group) or the perivascular axillary approach (AX group). A distal muscular contraction elicited by a nerve stimulator at current0.5 mA was used in all patients.At 30 and 45 minutes, complete loss of sensation was observed more often in group IC than AX in the cutaneous distribution of musculocutaneous nerve (62% v 30% [P.05] and 69% v 40%, respectively [P.05]), but at 60 minutes the difference was not statistically significant. In other areas, analgesia and motor block were achieved at a similar rate. In 3 patients surgery could not be performed under the block due to changes in schedule or the use of a brachial tourniquet. Patient satisfaction was equally high in both groups.Blockade of the musculocutaneous nerve developed faster with the infraclavicular coracoid approach than with the axillary approach. The infraclavicular coracoid approach may be preferable in patients scheduled for the creation of an arteriovenous fistula at the forearm.

Objectives Articaine, a popular and rapidly acting local anesthetic in dentistry, has been also found to be beneficial in ambulatory spinal anesthesia. Analgesia in the intraoperative and immediate postoperative period may be further improved by adding fentanyl to the local anesthetic solution for spinal anesthesia. The aim was to evaluate dose-dependency of analgesia and side effects associated with intrathecal fentanyl additive to articaine for spinal anesthesia in knee arthroscopy patients. Methods In this randomized, observer- and patient-blinded study, 90 adult patients scheduled for elective ambulatory knee arthroscopy under spinal anesthesia were randomized into three groups: plain articaine 60 mg with saline (group AF0), articaine 60 mg with fentanyl 10 A mu g (group AF10) or 20 A mu g (group AF20) in a total volume of 1.9 ml. The blinded observer tested the sensory and the motor block, and performed telephone interviews on the first and seventh postoperative days. Results The median (IQR) duration of sensory block at the dermatomal level of T10 was significantly longer in groups AF10, 69 min (56) and AF20, 69 min (45) than in group AF0, 41 min (35) (p = 0.013). Motor block duration was similar in all groups (median 120 min). Group AF20 patients experienced pruritus significantly more often than patients in the other groups (p = 0.039). No acute or late anesthetic side effects occurred, and satisfaction with the anesthetic technique was the same in all groups (97% satisfied). Conclusions Fentanyl 10 or 20 A mu g as additive to articaine for spinal anesthesia prolonged the duration of sensory block significantly and similarly. Fentanyl 20 A mu g was more often associated with pruritus than fentanyl 10 A mu g.

Study objective: Comparison of local anesthetic infiltration (LAI), spinal anesthesia (SPIN) and total intravenous anesthesia (TIVA) for open inguinal herniorrhaphy. We hypothesized that patients receiving LAI could be discharged faster than SPIN and TWA patients. Design: Randomized, prospective trial. Setting: University hospital day-surgery center. Patients: 156 adult male patients (ASA 1-3) undergoing day-case open inguinal herniorrhaphy. Interventions: Patients were randomized to either LAI (lidocaine + ropivacaine), SPIN (bupivacaine + fentanyl) or TWA (propofol + remifentanil). Perioperative Ringer infusion was 1.5 mL/h. Urinary bladder was scanned before and after surgery. Interviews were performed on postoperative days 1, 7 and 90. Measurements: Duration of surgery, duration of the patients' stay in the operating room and time until their readiness for discharge home. Patient satisfaction and adverse effects were registered. Main results: Surgery lasted longer in LAI group (median 40 min) than in SPIN group (35 min) (P = .003) and TWA group (33 min) (P

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.

Background Paracetamol (acetaminophen) is an effective analgesic and a weak inhibitor of cyclo-oxygenase (COX). Clinically paracetamol is often used together with traditional NSAIDs, which are strong inhibitors of COX. We studied binding of paracetamol to COX and its action on platelet function together with diclofenac. Methods Blood was collected from healthy donors and platelet function was assessed by photometric aggregometry, a platelet function analyser (PFA-100, Dade Behring, Deerfield, IL) and by measuring the release of thromboxane B(2) (TxB(2)), the stable metabolite of thromboxane A(2), after addition of paracetamol (10-80 microg ml(-1)). A concentration-inhibition relationship was established and the inhibition coefficient (K(i)) demonstrating 50% binding to COX was determined using a Schild-plot. Interaction of paracetamol (5-20 microg ml(-1)) and diclofenac (0.1-0.8 microg ml(-1)) was determined and an isobolographic analysis was performed. Results Paracetamol added to platelet-rich plasma (PRP) caused a concentration-dependent inhibition of platelet function. Photometric aggregometry and TxB(2) release was significantly inhibited by paracetamol from 10 microg ml(-1) onwards. The PFA-100 closure time was significantly prolonged by paracetamol at a high concentration only. K(i) was 15.2 microg ml(-1) with a 95% confidence interval of 11.8-18.6 microg ml(-1). Inhibition of aggregation by diclofenac was augmented by paracetamol. Isobolographic analysis showed synergism. Conclusions The 95% confidence interval of K(i) equals the antipyretic plasma concentration of paracetamol, i.e. 10-20 microg ml(-1). High doses of paracetamol and a combination of diclofenac and paracetamol cause platelet inhibition and thus may increase risk of surgical bleeding.

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.

Adequate intraoperative analgesia combined with faster mobilization might be achieved by replacing hyperbaric ropivacaine partly with fentanyl.Sixty spinal anesthesia patients were randomized into 2 groups of either fentanyl 20 microg mixed with hyperbaric ropivacaine 10 mg (group FR10) or hyperbaric ropivacaine 15 mg (group R15). Forty-five patients underwent inguinal hernia repair and 15 patients had lower extremity surgery. Sensory block was tested by pinprick, and motor block was tested by use of a modified Bromage scale at 5-minute intervals for 30 minutes, 15-minute intervals for 60 minutes, and at 30-minute intervals until full recovery.The groups did not differ significantly regarding success (27 of 30 [group FR10] and 29 of 30 [group R15]), median onset time (10 [5 to 25] v 10 [5 to 20] minutes) or median duration of T10 sensory block (55 [20 to 115] v 80 [5 to 170] minutes), respectively. Recovery from spinal block was significantly quicker in group FR10 than in group R15, recorded in ability to walk (2.5 hours v 3 hours [P=.017]), full motor recovery (1 hour v 1.5 hour [ P.001]), and sensory recovery to S1 (2.5 hours v 3.3 hours [ P=.026]). Pruritus occurred in 18 (60%) of group FR10 v 0 of group R15 patients ( P.001). This symptom was mild in all except 1 patient, who received ondansetron 8 mg IV. In the OR, the groups did not differ hemodynamically: 9 (30%) of the group FR10 and 10 (33%) of the group R15 patients, respectively, required medication for hypotension and/or bradycardia. Full motor block (Bromage 3) developed less frequently (P.001) in group FR10 patients than in group R15 patients (1 [3%] v 14 [47%]), and the group FR10 patients recovered faster in a median time of 60 v 90 minutes (P.001). In both groups, sensory and motor blocks were more extensive on the operative side compared with the nonoperative side ( P.001).Faster mobilization but equal onset and duration of analgesia were achieved with intrathecal hyperbaric ropivacaine 10 mg plus fentanyl 20 microg as compared with hyperbaric ropivacaine 15 mg.

The current recommendations regarding maximum doses of local anesthetics presented in textbooks, or by the responsible pharmaceutical companies, are not evidence based (ie, determined by randomized and controlled studies). Rather, decisions on recommending certain maximum local anesthetic doses have been made in part by extrapolations from animal experiments, clinical experiences from the use of various doses and measurement of blood concentrations, case reports of local anesthetic toxicity, and pharmacokinetic results. The common occurrence of central nervous system toxicity symptoms when large lidocaine doses were used in infiltration anesthesia led to the recommendation of just 200 mg as the maximum dose, which has remained unchanged for more than 50 years. In most cases, there is no scientific justification for presenting exact milligram doses or mg/kg doses as maximum dose recommendations. Instead, only clinically adequate and safe doses (ranges) that are block specific are justified, taking into consideration the site of local anesthetic injection and patient-related factors such as age, organ dysfunctions, and pregnancy, which may influence the effect and the pharmacokinetics of the local anesthetic. Epinephrine in concentrations of 2.5 to 5 microg/mL should be added to the local anesthetic solution when large doses are administered, providing there are no contraindications for the use of epinephrine. As a rule, conditions (eg, end-stage pregnancy, high age in epidural, or spinal block) or diseases (uremia) that may increase the rate of the initial uptake of the local anesthetic are indications to reduce the dose in comparison to one normally used for young, healthy, and nonpregnant adults. On the other hand, the reduced clearance of local anesthetics associated with renal, hepatic, and cardiac diseases is the most important reason to reduce the dose for repeated or continuous administration. The magnitude of the reduction should be related to the expected influence of the pharmacodynamic or pharmacokinetic change.

Ropivacaine, which blocks sensory nerve fibers more readily than motor fibers, is considered to be less potent than bupivacaine. Our hypothesis was that, when used in spinal anesthesia for day surgery, ropivacaine 15 and 20 mg would provide faster motor recovery than bupivacaine 10 mg. This prospective, randomized, double-blinded study included 90 ambulatory lower-extremity surgery patients who received 2 mL of ropivacaine 1%, ropivacaine 0.75%, or bupivacaine 0.5%. Motor block was tested with the Bromage scale, and sensory block was tested with pinprick. Ropivacaine 15 mg provided faster recovery of motor block (150 min) than did bupivacaine 10 mg (210 min; P = 0.005), but the median duration of sensory block at T10 (140 min) did not differ significantly from that with bupivacaine 10 mg (140 min). The median duration of sensory block at T10 was significantly longer with ropivacaine 20 mg (170 min) than with bupivacaine 10 mg (140 min; P = 0.005), but the median recovery from motor block (210 min) did not differ significantly. We conclude that the duration of sensory block of ropivacaine was two thirds and the duration of motor block was half when compared with bupivacaine, with calculations based on the duration-per-milligram of the local anesthetic.

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.

Introduction: The Resuscitation 2000 Guidelines recommends amiodarone as the antiarrhythmic drug of choice in treatment of resistant ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). Amiodarone has been associated with side-effects and difficulty of administration, due to recommended dilution, rendering it suboptimal for out-of-hospital cardiac arrest (CA) management. In the present study we report experiences and side-effects of the use of undiluted amiodarone in CA management in Helsinki Emergency Medical Service (EMS) during a 2-year period. Methods: On October 1, the Resuscitation 2000 Guidelines were put into practice in Helsinki EMS. Thus, in the cardiac arrest treatment protocol, after three ineffective shocks and 1 mg of adrenaline (epinephrine), a bolus of 300 mg of undiluted amiodarone (Cordarone® 50 mg ml−1, Sanofi-Synthelabo, Helsinki, Finland) was administered into a vein located as centrally as possible. The Helsinki EMS performs systematic data collection according to the Utstein Guidelines. The blood pressure levels, heart rates and the need for vasopressors, of the patients with sustained return of spontaneous circulation (ROSC), were collected from the ambulance charts. Results: During October 1, 2000 and September 30, 2002, 712 patients were considered for resuscitation and 566 were resuscitated. The initial rhythms were as follows: 32% had VF/VT, 36% had asystole and 32% had pulseless electrical activity (PEA). Of the 180 patients with VF/VT, 75 (42%) received undiluted amiodarone in addition to other resuscitative measures. Of the patients with asystole or PEA, 12 (6%) and 18 (10%), respectively, received amiodarone. The blood pressure levels and the need vasopressors after ROSC and during transportation to the hospital were similar among the patients who received and those who did not receive amiodarone. Conclusions: The present study suggests that amiodarone can be administered undiluted without unmanageable haemodynamical side-effects in the treatment of out-of-hospital cardiac arrest. This is likely to save time and simplifies the treatment protocol in the prehospital setting.

Background: Preincisional ilioinguinal and iliohypogastric nerve block (IINB) reduces postoperative analgesics after inguinal herniorrhaphy. The effect of an IINB on postoperative pain and discharge profile was therefore studied in day-surgery patients undergoing inguinal herniorrhaphy with general or spinal anaesthesia. Methods: Seventy ASA I–II adult patients scheduled for inguinal herniorrhaphy received an IINB before the surgical incision with 15 ml of 0.5% bupivacaine. In a randomized fashion half of them received general anaesthesia with spontaneous breathing via a laryngeal mask (GA-group) and the other half received spinal anaesthesia with 5 mg of bupivacaine diluted with sterile water to 2.5-ml volume (SPIN-group). In the postanaesthesia care unit (PACU), pain was assessed on a scale from 0 to 10 (VAS) and ketorolac 30 mg i.v. (VAS

UNLABELLED The cause of transient neurologic symptoms (TNSs) after lidocaine spinal anesthesia remains unclear. It has been proposed that early ambulation after spinal anesthesia contributes to the development of TNSs. We evaluated the influence of ambulation time on the occurrence of TNSs after spinal anesthesia with 50 mg of 2% plain lidocaine for knee arthroscopy. One-hundred-twenty patients undergoing knee arthroscopy (ASA physical status 1-2) were randomized into 3 groups, i.e., early (Group E), 6-h (Group 6-h), or late ambulation (Group L) groups. In Group E, ambulation was allowed as early as possible after regression of spinal block (on average 229 +/- 21 min; range, 135-247 min). In Group 6-h, the patients remained in bed for approximately 6 h after the block and in Group L until the next morning. The patient groups were comparable with respect to demographic, anesthetic, and surgical variables. The overall incidence of TNSs was 16%. TNSs occurred in 3 patients of Group E (7.5%), in 11 patients of Group 6-h (28%), and in 5 patients of Group L (13%). No significant differences were detected between the patients with and without TNSs. Early ambulation was not found to be a risk factor for TNSs after spinal anesthesia with 50 mg of 2% lidocaine. IMPLICATIONS This study shows that early ambulation time does not increase the incidence of transient neurologic symptoms after spinal anesthesia with 50 mg of 2% lidocaine for elective knee arthroscopy.

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.

Reports on the efficacy and pharmacokinetics of local anesthetics in uremic patients have been controversial. Our study involved 29 uremic and 28 nonuremic patients. We performed axillary block with ropivacaine 300 mg (50 mL). Venous blood samples were drawn for 24 h for assay of total and unbound plasma ropivacaine, 3-hydroxyropivacaine, pipecoloxylidide (PPX), and serum alpha(1)-acid glycoprotein (AAG). Block quality was similar in both groups. No toxicity occurred. Plasma clearance of ropivacaine was smaller and the area under the concentration-time curve of ropivacaine, 3-hydroxyropivacaine, and PPX larger in the uremic patients. The plasma concentration of PPX increased until 24 h in uremic patients whose AAG concentrations were also larger throughout the study. The free fraction of ropivacaine in plasma was smaller in the uremic group when measured 60 min and 12 h after the block, but the unbound concentration of ropivacaine was larger in the uremic group at 12 h. Enhanced absorption of ropivacaine into circulation, increased binding to AAG, and probably reduced urinary excretion of the metabolites lead to larger total plasma concentrations of ropivacaine and its main metabolites in uremic patients.

Objective. To describe the prehospital use of a continuous positive airway pressure (CPAP) system for the treatment of presumed acute severe pulmonary edema (ASPE). Methods. The efficacy of prehospital CPAP treatment was analyzed in terms of changes in oxygen saturation, need for intubation or ventilatory support, and possible morbidity associated with the CPAP therapy. This was a retrospective cohort study conducted in the mobile intensive care unit of a university hospital. Participants included all consecutive patients with a clinical picture of ASPE treated by a mobile intensive care unit between January 1, 1998, and December 31, 1999. Results. 121 patients were included in this study. 116 patients received prehospital CPAP therapy. Two patients (1.7%) from the CPAP-treated patients were intubated in the field. A total of six patients required endotracheal intubation before hospital, and six other patients after that. After the beginning of CPAP treatment, there was statistically significant elevation...

The production of monoethylglycine xylidide (MEGX) from lidocaine is thought to be dependent on hepatic blood flow. We assessed the relationship between hepatosplanchnic blood flow, lidocaine uptake, and the production of MEGX from lidocaine in seven patients after cardiac surgery and in nine septic patients. Systemic (pulmonary artery catheter) and splanchnic (hepatic vein catheter and dye dilution) hemodynamics and arterial and hepatic venous lidocaine and MEGX concentrations were measured after a lidocaine bolus injection (1 mg/kg) before and 90 min after increasing cardiac output by at least 25% with dopamine. Dopamine infusion [in cardiac surgery patients 4.2 (1.4-8.5) microg x kg(-1) x min(-1) (median, range) and in septic patients 4.0 (2.1-9.0) microg x kg(-1) x min(-1)] increased splanchnic blood flow in cardiac surgery patients from 0.65 (0.12) L x min(-1) x m(-2) to 0.84 (0.14) L x min(-1) x m(-2) mean (standard deviation) P = 0.018) and in septic patients from 0.91 (0.32) L x min(-1) x m(-2) to 1.12 (0.40) L x min(-1) x m(-2) (P = 0.038). Splanchnic MEGX production for the 30 min after lidocaine injection was higher in cardiac surgery patients than in septic patients both at baseline [4130 (1100) microg x m(-2) vs. 930 (420) microg x m(-2) (P < 0.005)] and afterdopamine infusion [4480 (1000) microg x m(-2) vs. 1090 (620) microg x m(-2) (P = 0.005)]. We found no correlation between changes in MEGX production and changes in splanchnic blood flow. Patients with sepsis have severe impairment of cytochrome P450-dependent liver function, which is not influenced by acute changes in hepatosplanchnic blood flow. MEGX production cannot be used as an estimate of changes in splanchnic blood flow.

Background: Postarthroscopy analgesia has been provided with intra-articular bupivacaine, but reported results are conflicting regarding efficacy and the duration of analgesia. The immediate and long-term effects of intra-articular bupivacaine with epinephrine after arthroscopic knee surgery were therefore studied in a day surgery setting. Methods: 120 ASA I–II patients scheduled for arthroscopic knee surgery were given general anesthesia with spontaneous breathing via a laryngeal mask. In a randomized and blinded fashion half of them received, at the end of surgery, intra-articularly 20 mL 0.5% bupivacaine with epinephrine (B + E-group) and the other half 20 mL saline with epinephrine (S + E-group). All patients received ketoprofen 100 mg i.v. during surgery and another 100 mg 2–3 h postoperatively. The patients were observed for about 4.5 h in the day surgery unit before discharge. Results: The results showed that in comparison with the S + E-group, significantly fewer patients in the B + E-group needed analgesics (P

Background: During recent years in-hospital cardiopulmonary resuscitation (CPR) management has received much attention. This can be attributed to the Utstein model for in-hospital CPR developed in 1997. The present status of in-hospital resuscitation management in Finnish hospitals is not known. Therefore, a study was designed to describe the organization of training and clinical management of CPR in Finnish hospitals of different levels of care. Methods: In the summer of 2000, we performed a cross-sectional mail survey throughout Finland, including all district, central and university hospitals. The questionnaire outlined in detail in-hospital resuscitation management and training. For analysis the hospitals were divided into primary, secondary and tertiary groups, depending on levels of care. Results: Most hospitals (72%) reported having a physician or a nurse in charge of resuscitation management and training. Training in advanced life support was more common among nurses (80%) than among physicians (53%). Suprisingly, a majority of respondents (75%) reported that they felt training in CPR was insufficient. On the general wards and on wards treating cardiac patients, defibrillation was in most cases performed by a physician (91% and 51%, respectively), and less often by a nurse (16% and 31%, respectively). In the secondary and tertiary hospitals cardiac arrest was managed by a cardiac arrest team (53% and 62%, respectively) and in the primary hospitals by the ward physician (56%), anesthesiologist or emergency physician on call (44%). Most hospitals used do-not-resuscitate orders (83%) but only 33% of the hospitals had a unified style of notation. Systematic data collection was practised in 55% of hospitals, predominantly by using a model of their own. Only a few hospitals (11%) used the in-hospital Utstein model. Conclusion: Our study showed that more attention needs to be paid to CPR management in Finnish hospitals. At present, 25% of hospitals do not have an appointed physician or nurse in charge of organizing CPR management. The study also revealed a lack of regular organized training in resuscitation for physicians. Fiftyfive per cent of hospitals practise systematic data collection, but only 11% according to the Utstein template; and without which further quality assurance is difficult.

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.