The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs.

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.

Intravenous lipid emulsion for levobupivacaine intoxication in acidotic and hypoxaemic pigs.

Intravenous lipid emulsion is, in some countries, the recommended treatment for local anaesthetic toxicity. Systemic local anaesthetic toxicity results in hypoxaemia and acidosis, and whether this influences the effects of lipid therapy on drug concentrations and cardiovascular recovery is currently unknown. Twenty anaesthetised pigs were given a 3-mg/kg bolus of levobupivacaine followed by a five minute phase of hypoventilation and 1 mmol/kg of lactic acid in one minute. After lactic acid infusion, pigs were treated, in randomised order, with either 20% lipid emulsion or Ringer's acetate for 30 min: a 1.5-ml/kg bolus followed by a 0.25-ml/kg/minute infusion. Haemodynamic parameters were recorded and blood samples were collected for pharmacokinetic analysis. There was no difference between the groups in the area under the plasma levobupivacaine concentration-time curve (AUC) or between that and AUC of unentrapped levobupivacaine in the Lipid group, or in the plasma half-lives. The cardiovascular outcome and normalisation of the electrocardiogram were similar in both groups. Five pigs developed marked hypotension: one in both groups died, while two in the Lipid group and one in the Ringer group needed adrenaline. Administration of lipid emulsion did not improve cardiovascular recovery from levobupivacaine toxicity exacerbated by acidosis and hypoxaemia. Lipid emulsion did not entrap levobupivacaine or affect levobupivacaine pharmacokinetics.

Incidence of severe local anaesthetic toxicity and adoption of lipid rescue in Finnish anaesthesia departments in 2011-2013.

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.

National critical incident reporting systems relevant to anaesthesia: a European survey.

BACKGROUND: Critical incident reporting is a key tool in the promotion of patient safety in anaesthesia. METHODS: We surveyed representatives of national incident reporting systems in six European countries, inviting information on scope and organization, and intelligence on factors determining success and failure. RESULTS: Some systems are government-run and nationally conceived; others started out as small, specialty-focused initiatives, which have since acquired a national reach. However, both national co-ordination and specialty enthusiasts seem to be necessary for an optimally functioning system. The role of reporting culture, definitional issues, and dissemination is discussed. CONCLUSIONS: We make recommendations for others intending to start new systems and speculate on the prospects for sharing patient safety lessons relevant to anaesthesia at European level.

Pre-medication with sublingual fentanyl did not relieve pain associated with bone marrow aspiration and biopsy: a randomized feasibility trial.

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.

Chloroprocaine 40 mg produces shorter spinal block than articaine 40 mg in day-case knee arthroscopy patients.

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 < 36 kg/m(2) ) scheduled for day-case knee arthroscopy received either articaine 40 mg (20 mg/ml) (group A40, n = 16) or chloroprocaine 40 mg (20 mg/ml) (group C40, n = 18) intrathecally. Telephone interviews were performed on the first and seventh postoperative day to disclose possible side effects, e.g. transient neurological symptoms (TNS). RESULTS: The groups were comparable regarding demographic data, onset and maximal spread of spinal anaesthesia, and duration of surgery. Surgery could be performed successfully under spinal anaesthesia except once in A40 (insufficient block) and once in C40 (prolonged surgery). Complete recovery was significantly slower in A40 vs. C40 for both motor block (105 (94/120) vs. 75 (71/90) min) [P < 0.001, Mann-Whitney U-test (MW-U)] and sensory block [135 (109/176) vs. 105 min (90/124)] (P < 0.02, MW-U), respectively [data are median (25th/75th percentiles)]. One patient from A40 showed mild TNS. CONCLUSION: Both A40 and C40 provided mainly adequate spinal anaesthesia for day-case knee arthroscopy. While onset and maximal spread were comparable, the recovery from motor block was clearly faster with chloroprocaine after equivalent doses of spinal articaine and chloroprocaine.

Effect of intravenous lipid emulsion on bupivacaine plasma concentration in humans.

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<0.02). However, there were no differences in un-entrapped (non-lipid bound) or free (non-protein bound) bupivacaine plasma concentrations during the infusion. Intravenous lipid emulsion infusion reduced the context-sensitive half-life of total plasma bupivacaine from 45 (95% CI 32-76)min to 25 (95% CI 20-33)min; p=0.01. We observed no significant adverse effects of lipid emulsion. In conclusion, lipid emulsion may slightly increase the rate of bupivacaine tissue distribution. No 'lipid sink' effect was observed with the non-toxic dose of bupivacaine used.

Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial.

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.

Pharmacokinetics of ropivacaine in patients with chronic renal failure.

BACKGROUND: As ropivacaine and its metabolites are excreted by the kidneys, we studied their disposition in subjects with renal dysfunction. METHODS: Twenty patients with moderate or severe renal insufficiency and 10 healthy volunteers received ropivacaine 1 mg kg(-1) i.v. over 30 min. The concentrations of ropivacaine and its main metabolites, pipecoloxylidide (PPX) and 3-hydroxy-ropivacaine, were measured in plasma and urine for 16-48 h. The relationship between pharmacokinetic parameters and creatinine clearance (CL(CR)) was assessed. A model for estimating non-renal clearance of a metabolite of ropivacaine is described. RESULTS: Renal dysfunction had little or no influence on the pharmacokinetics of ropivacaine. The median plasma concentrations of unbound ropivacaine were similar in uraemic and non-uraemic subjects. Renal clearance of PPX correlated significantly with CL(CR) (R(2)=0.81). Lack of correlation between total PPX exposure, expressed as area under the total plasma concentration-time curve from zero to infinity, and CL(CR) suggests that the clearance of PPX also includes non-renal elimination. However, in two uraemic patients, there was increased exposure to PPX resulting from low non-renal elimination. CONCLUSIONS: The pharmacokinetics of ropivacaine is not affected by renal failure. Although the renal clearance of PPX correlates with CL(CR), non-renal elimination seems to compensate for reduced renal clearance in most patients. PPX may accumulate in plasma during long-term postoperative infusions, in particular in patients with co-existing low non-renal elimination. Systemic toxicity is still unlikely because PPX is markedly less toxic than ropivacaine.

Chloroprocaine vs. articaine as spinal anaesthetics for day-case knee arthroscopy.

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<36 kg/m2) underwent day-case knee arthroscopy under spinal anaesthesia with either 40 mg of plain chloroprocaine (20 mg/ml) (group C40; n=39) or 60 mg of plain articaine (40 mg/ml) (group A60; n=39). Study parameters included the onset, degree, and regression of both sensory and motor block. Standardised telephone interviews on the first and seventh post-operative day were aimed at detecting any untoward sequelae, e.g., transient neurologic symptoms (TNSs). RESULTS: The groups were comparable regarding demographic data, onset and maximal spread of spinal anaesthesia, and duration of surgery. All arthroscopies were performed successfully under spinal anaesthesia, except for one patient (C40, unforeseen delay in the start of surgery). The duration of sensory block≥dermatome L1 was significantly shorter in C40 vs. A60. Correspondingly, complete recovery was significantly faster (P<0.0001, Mann-Whitney U-test) in C40 vs. A60 for both motor [75 (60/90) vs. 135 (105/150) min] and sensory [105 (105/135) vs. 165 (135/180) min] block, respectively [data are median (25th/75th percentiles)]. No TNSs were noted. CONCLUSIONS: Both anaesthetics used provided a rapid onset of spinal anaesthesia of about 1 h and were satisfactory for day-case knee arthroscopy. Recovery, however, was significantly faster in group C40. The data add to earlier results that TNSs seem to be uncommon after spinal chloroprocaine and articaine.

Evaluation of easily applicable pain measurement tools for the assessment of pain in demented patients.

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> or =24, patients were able to use all four scales rather successfully. In the other groups (MMSE 17-23, 11-16 and < or =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<0.01). The estimations of intensity and frequency of pain performed by nurses failed to correlate with the patient's own pain intensity estimations. CONCLUSION: Scoring of pain with RWS, FPS and VAS seems to be feasible in elderly patients with a normal cognitive dysfunction. In our study VRS appeared to be applicable in the elderly with a clear cognitive dysfunction, i.e., with MMSE<17.

Comparison of effects and plasma concentrations of opioids between elderly and middle-aged patients after cardiac surgery.

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 (>or=75 years, gender M9/F21) and 20 (

Comparison of hyperbaric and plain articaine in spinal anaesthesia for open inguinal hernia repair.

BACKGROUND: Fast onset and short duration are prominent properties of the amide-type local anaesthetic articaine. Similar to bupivacaine, a hyperbaric solution of articaine may produce faster onset and shorter duration of spinal anaesthesia than a plain solution. METHODS: Patients undergoing open inguinal hernia repair received in random order articaine 84 mg in either hyperbaric (HyperA, n=49) or plain solution (PlainA, n=48) intrathecally. A blinded observer tested the dermatomal spread (pinprick) and motor block (Bromage scale). RESULTS: Median (range) onset time to the T(10) dermatome was 2 (2-8) (n=46) and 6 (2-30) min (n=39) (P<0.001), and the duration of the sensory block at (or above) the T(10) dermatome was 86 (39-148) and 69 (15-118) min (P=0.007), in Groups HyperA and PlainA, respectively. Peak sensory block was greater in Group HyperA T(4) (L(2)-C(2)) than in Group PlainA T(8)-T(7) (L(3)-T(3)) dermatome, median (range), P<0.001. Spread of the block to the cervical dermatomes associated with hypotension occurred in three patients of Group HyperA (one patient C(2) and two C(4)). The sensory block resolved to the S(2) dermatome significantly faster in Group HyperA, 2.5 (1.5-4.5) h, than in Group PlainA, 3.5 (2.0-4.5) h (P<0.001). Median duration of the motor block was significantly shorter in Group HyperA, 2.0 (1.3-3.5) vs 3.0 (1.5-4.0) h (P<0.001). CONCLUSIONS: Hyperbaric articaine 84 mg had a faster onset and shorter duration of spinal anaesthesia than the plain solution.

I.V. ropivacaine compared with lidocaine for the treatment of tinnitus.

BACKGROUND: I.V. lidocaine has been used to ameliorate tinnitus, but in general its effect has been limited. The longer acting local anaesthetic ropivacaine may be more effective. METHODS: A total of 19 randomized, double-blind, cross-over study patients suffering from chronic tinnitus were given a 30 min i.v. infusion of ropivacaine or lidocaine 1.5 mg kg(-1) at an interval of 2-3 months. The intensity of tinnitus was evaluated on tinnitus handicap inventory (THI) scale and on the visual analogue scale (VAS). Plasma ropivacaine and lidocaine concentrations were determined. RESULTS: In both treatments, the infusion decreased the VAS score significantly. At the end of infusion, a > or =50% reduction in VAS score was observed in five patients by ropivacaine and in one patient by lidocaine, but this effect was sustained for 1 h only in three patients. However, the THI scores did not differ significantly within or between treatments. On the post-infusion day, three patients after ropivacaine and five after lidocaine treatment had > or =30% improvement in the THI score. Four weeks later, one patient after ropivacaine and two after lidocaine had a > or =30% reduction in the THI score. One patient developed seizures soon after ropivacaine infusion from which he recovered uneventfully. His plasma concentration of ropivacaine was 1817 ng ml(-1). The highest individual ropivacaine and lidocaine concentrations were 3483 and 1680 ng ml(-1), respectively. CONCLUSIONS: Temporary clinically significant alleviation of tinnitus was observed only in a few individuals after both i.v. ropivacaine and lidocaine. The toxicity of ropivacaine limits its usefulness.

Applicability of tools to assess pain in elderly patients after cardiac surgery.

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<0.001) and weaker with the VRS (r=0.666, P<0.001) measurements. Pain measurements with the FPS correlated well with the VAS (r=0.873, P<0.001) and weaker with the VRS (r=0.583, P<0.001) measurements. With all scales, success rates improved during the study period. CONCLUSION: In elderly patients, immediately after cardiac surgery, the VRS is the most feasible pain scale, followed by the RWS. The traditional 10-cm VAS is unsuitable for pain measurement in this population.

Interprofessional education of medical students and paramedics in emergency medicine.

BACKGROUND: Emergency medicine is team work from the field to the hospital and therefore it is also important for physicians to understand the work of paramedics, and vice versa. Interprofessional emergency medicine education for medical and paramedic students in Helsinki was started in 2001. It consisted of a 15 European credit transfer system (ECTS) credits programme combining 22 students in 2001. In 2005, the number of students had increased to 25. The programme consisted of three parts: acute illness in childhood and adults (AI), advanced life support (ALS) and trauma life support (TLS). In this paper, we describe the concept of interprofessional education of medical students and paramedics in emergency medicine. METHODS: After finishing the programmes in 2001 and in 2005, the students' opinions regarding the education were collected using a standardized questionnaire. RESULTS: There were good ratings for the courses in AI (2001 vs. 2005, whole group; 4.3 +/- 0.7 vs. 4.2 +/- 0.4, P = 0.44) ALS (4.7 +/- 0.5 vs. 4.4 +/- 0.5, P = 0.06) and TLS (3.9 +/- 0.7 vs. 4.4 +/- 0.5, P = 0.01) in both years. Most of the medical students considered that this kind of co-education should be arranged for all medical students (2001 vs. 2005; 4.8 +/- 0.6 vs. 4.4 +/- 0.5, P = 0.02) and should be obligatory (3.5 +/- 1.5 vs. 3.1 +/- 1.3, P = 0.35). CONCLUSIONS: Co-education was well received and determined by the students as an effective way of improving their knowledge of emergency medicine and medical skills. The programme was rated as very useful and it should be included in the educational curriculum of both student groups.