Summary

AstraZeneca (the manufacturer of Diprivan™) presents its review of the history of the so-called ‘propofol infusion syndrome’, highlighting the difficulties in analysing the incomplete information available. Theories as to its causality are presented and discussed; these include mitochondrial toxicity, mitochondrial defects, impaired tissue oxygenation and carbohydrate deficiency. A review of published and confidential safety data is presented and discussed; it concludes that the major risk factors for its development appear to be poor oxygen delivery, sepsis, serious cerebral injury and high propofol dosage. In some reports an increasing lipaemia was noted and was likely to be due to a failure of hepatic lipid regulation, possibly related to poor oxygenation and/or possibly a lack of glucose. In some cases an increasing lipaemia was the first indication of impending ‘propofol infusion syndrome’ onset and it should not be viewed as a benign sign. The lipaemia can lead to sequestration of propofol into the lipid phase, leading to lowered free propofol levels and apparent insensitivity to propofol. In conclusion AstraZeneca advocates good haemodynamic and oxygen delivery management, adequate glucose provision, adherence to recommended propofol dosing regimes together with active management of lipaemias to both prevent and treat ‘propofol infusion syndrome’.

Summary

Background: The aim of this prospective, randomized, blinded study was to compare analgesic efficacy of continuous paravertebral and epidural analgesia for post-thoracotomy pain. Methods: Forty-two ASA physical status II–III patients undergoing lung resection surgery were randomly allocated to receive post-thoracotomy analgesia with either a thoracic epidural (group EPI, n = 21) or paravertebral (group PVB, n = 21) infusion of 0.2% ropivacaine (infusion rate: 5–10 mL h−1). The degree of pain at rest and during coughing, haemodynamic variables and blood gas analysis were recorded every 12 h for the first 48 h. Results: The area under the curve of the visual analogue pain score during coughing over time was 192 (60–444) cm h−1 in group EPI and 228 (72–456) cm h−1 in group PVB (P = 0.29). Rescue morphine analgesia was required in four patients of group EPI (19%) and five patients of group PVB (23%) (P = 0.99). The PaO2/FiO2 ratio reduced significantly from baseline values in both groups without between-group differences. The median (range) percentage reduction of systolic arterial pressure from baseline was −9 (0 to −9)% in group PVB and −17 (0 to −38)% in group EPI (P = 0.02); while clinically relevant hypotension (systolic arterial pressure decrease >30% of baseline) was observed in four patients of group EPI only (19%) (P = 0.04). Patient satisfaction with the analgesia technique was 8.5 (8–9.8) cm in group EPI and 9 (7.5–10) cm in group PVB (P = 0.65). Conclusions: Continuous thoracic paravertebral analgesia is as effective as epidural blockade in controlling post-thoracotomy pain, but is associated with less haemodynamic effects.

Summary

Background and objectives: To compare pain relief and motor impairment of 0.25% levobupivacaine with either an equivalent (0.25%) or equipotent (0.4%) concentration of ropivacaine for continuous interscalene block after open shoulder surgery. Methods: Seventy-two adult patients scheduled for elective major shoulder surgery received an interscalene injection of mepivacaine 1.5% 30 mL followed by 24 h patient-controlled interscalene analgesia (basal infusion rate: 5 mL h−1; incremental bolus: 2 mL; lockout period: 10 min; maximum boluses per hour: 4) with either 0.25% levobupivacaine (n = 24), 0.25% ropivacaine (n = 24) or 0.4% ropivacaine (n = 24). A blinded observer recorded the evolution of pain relief and recovery of motor block during the first 24 h. Motor function was assessed as the maximum pressure developed while squeezing a sphygmomanometer cuff with the blocked hand. The reduction from preoperative values was considered as an index of motor impairment. Results: No differences were reported among the three groups in the quality of postoperative analgesia. The number of incremental patient-controlled interscalene analgesia doses, total volume of local anaesthetic infused during the 24-h patient-controlled interscalene analgesia, and number of rescue ketoprofen analgesia were higher in the ropivacaine 0.25% group than in the other two groups ( P = 0.0005). The hand strength recovered to ≥90% of baseline values within the first 24 h of infusion in all groups, without differences among the three groups. Conclusion: When providing patient-controlled interscalene analgesia after open shoulder surgery 0.25% levobupivacaine and 0.4% ropivacaine performed equally in terms of pain relief, motor block and number of patient-controlled boluses required, while patients receiving 0.25% ropivacaine needed significantly more boluses and rescue analgesia to control their pain.

Summary

Background and objectives: Postoperative pain is a common problem following ambulatory breast augmentation surgery. This study was performed to compare standard of care (oral analgesics) with patient-controlled incisional regional analgesia (PCRA) for postoperative pain management at home for 48 h. A second aim was to compare the analgesic efficacy of ropivacaine 0.25% vs. 0.5%. Methods: Surgery was performed under local anaesthesia and monitored anesthesia care. Sixty adults (ASA 1–2) were randomized to one of two groups. Patients in Group PCRA could self-administer ropivacaine 0.25% 10 mL in the left breast and ropivacaine 0.5% in the right breast. Patients in Group T (tablets) received our standard of care treatment, i.e. oral paracetamol 1 g four times a day and oral ibuprofen 500 mg three times a day. Parameters measured included: analgesic requirements (in post-anesthesia care unit, PACU and post-discharge), pain intensity (visual analogue scale), patient satisfaction, global analgesia, side-effects, and quality of recovery. Results: Pain scores were significantly lower in Group PCRA compared to Group T at all time periods (P < 0.05). No differences were found in pain scores between the right and left breasts. Significantly more patients in Group T requested analgesics in the recovery unit (27 vs. 7; P = 0.001) and also at home (20 vs. 11; P < 0.02). More patients in the tablet group had nausea and vomiting (10 vs. 3; P < 0.05). Global analgesia on day 2 was significantly better in PCRA group; however, patient satisfaction was similar in both groups. More patients in the tablet group had sleep disturbance and woke up at night due to pain. Conclusions: Pain relief after ambulatory breast augmentation is superior with incisional PCRA when compared to oral analgesic combination of paracetamol and ibuprofen. Incisional PCRA was associated with minimal side-effects and less sleep disturbance. There was no difference in the analgesic efficacy between ropivacaine 0.25% and 0.5%.

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Background: In this prospective, randomized, double-blind, controlled study, we investigated the sensory, motor and analgesic block characteristics of S(+) ketamine, fentanyl and saline given intrathecally (IT) in addition to 0.5% plain bupivacaine (10 mg) for spinal analgesia. Methods: Ninety ASA I or II adult patients undergoing Caesarean section were randomly allocated to receive 1.0 mL of 0.9% saline in Group S (n = 30), 0.05 mg kg−1 of S(+) ketamine (1.0 mL) in Group K (n =30) or 25 μg (1.0 mL) of fentanyl in Group F (n =30) following 10 mg of plain bupivacaine 0.5% IT. We recorded onset and duration of sensory and motor block, time to reach the maximal dermatomal level of sensory block and duration of spinal analgesia. Results: The onset time of sensory and motor block was significantly shorter in Groups K and F than in Group S (P < 0.014). Their duration was significantly longer in Group F than in Groups K and S (P < 0.009). The time to reach the maximal dermatomal level of sensory block was significantly shorter in Groups K and F than in Group S (P < 0.001). The duration of spinal analgesia was significantly longer in Group F than in Groups K and S (P < 0.001). Conclusion: In patients undergoing Caesarean section with spinal analgesia, the addition of S(+) ketamine (0.05 mg kg−1) IT to 10 mg of spinal plain bupivacaine (0.5%) led to rapid onset of both sensory and motor blockade and enhanced the segmental spread of spinal block without prolonging the duration of spinal analgesia, whereas fentanyl provided prolonged analgesia.

Summary

Background and objective: The use of a pneumatic tourniquet can induce muscular and neurological complications in the operated limb. The genesis of these injuries could involve an ischaemia/reperfusion phenomenon and a compression under the cuff. We evaluated effects of an antioxidant, acetylcysteine and ischaemic preconditioning on the rhabdomyolysis and postoperative pain following a knee ligamentoplasty using a pneumatic tourniquet. Methods: We included 31 patients scheduled for a knee ligamentoplasty randomly assigned in three groups (control, acetylcysteine 1200 mg the day before and 600 mg at the operative day, ischaemic preconditioning). Results: There was a moderate rise in myoglobin and creatinine phosphokinase with no significant difference between the three groups. The muscular functional parameters were similar in all the groups. However, the morphine consumption within the first 48 h was smaller in the treatment groups (0.22 ± 0.31 mg kg−1 and 0.22 ± 0.23 mg kg−1 in the preconditioning and antioxidant groups, respectively) than in the control group (0.47 ± 0.33 mg kg−1, P <0.05). Conclusions: Acetylcysteine and ischaemic preconditioning do not decrease the extent of rhabdomyolysis related to the use of a pneumatic tourniquet and do not improve the postoperative muscle recovery. On the other hand, they allow a significant reduction in the postoperative morphine consumption.

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Background and objectives: To analyse the prevalence of positive prick-tests to all medicaments normally checked in allergy units when a patient is suspected of being allergic to anaesthetics. To establish the degree of agreement between the antecedents of a previous history of an allergic reaction to a medicament and the positive result, or not, to the specific prick-test for the said medicament. Methods: This was a prospective study, during 2003 and 2004, which analysed 473 patients referred by their doctors to allergy units to make retrospective diagnoses of an allergy to a drug. The prick-test was done using the undiluted drug. All patients were tested for 41 drugs. These include antibiotics, trimethoprim–sulphamethoxazole, non-steroidal anti-inflammatory drugs (NSAIDs) and perioperative drugs (PD): neuromuscular blocking drugs, latex, iodine, local anaesthetics, hypnotics, opioids and coadjuvants. Cohen's Kappa Index was used to determine the degree of agreement. Results: 71.5% of patients studied presented a positive prick-test. The largest number of positive cases was found in antibiotics (56.4%), followed by PD (15.6%), NSAIDs (14.4%) and trimethoprim–sulphamethoxazole (12.7%). Among PD, the highest prevalence of positive prick-tests was found for neuromuscular blocking drugs (5.3%). Agreement between the substance suspected of causing the allergic reaction and the positive prick-test was excellent for penicillin (Kappa = 0.74) and other antibiotics (Kappa = 0.721) and good for NSAIDs (Kappa = 0.47) and iodine (Kappa = 0.54). Conclusions: The prevalence of patients with positive prick-tests to PD occurred in 15.6% in this prospective cohort. Neuromuscular blocking drugs were found to have the highest prevalence of positive prick-tests. There is positive agreement when the substance responsible for the allergic reaction is suspected, otherwise agreement is low.

Summary

Background and objectives: The aim of our study was to investigate the antimicrobial effects of dexmedetomidine and etomidate-lipuro, and to compare these effects with those of midazolam and propofol on Staphylococcus aureus, Escherichia coli, Pseudomonas aeroginosa, Acinetobacter baumannii and extended-spectrum beta-lactamase Escherichia coli ( E. coli ESBL). Methods: All hypnotic dilutions were exposed to micro-organisms for 0, 30, 60, 120 and 240 min at room temperature in vitro. The inoculums taken from diluted suspensions were re-inoculated on blood agar and incubated for 18–24 h at 35°C after which a count of the colonies was compared. Results: Midazolam reduced the viable cells of S. aureus at 30, 60, 120 and 240 min, and also completely inhibited the growth of E. coli, P. aeroginosa, A. baumannii and E. coli ESBL. Dexmedetomidine, etomidate-lipuro and propofol, however, did not inhibit any of the micro-organisms tested. Conclusion:In vitro, midazolam had an antimicrobial effect on E. coli, P. aeroginosa, A. baumannii and E. coli ESBL. Like propofol and dexmedetomidine, etomidate-lipuro had no antimicrobial effect on any of the micro-organisms tested.

Summary

Background and objective: Proinflammatory cytokines as well as nitric oxide (NO) play a major role in mediating the response to lipopolysaccharide (LPS). The present study tested the hypothesis that LPS induces proinflammatory cytokines in the lung via the Toll-like receptor 4 (TLR4)/CD14 signalling cascade. Methods: Control mice and TLR4-deficient (TLR4-D) mice were used to test TLR4-mediated effects of LPS. Both strains received either Escherichia coli LPS (20 mg kg−1 intraperitoneal) or saline and their lungs were collected at different time points. Pulmonary nuclear factor κB (NFκB) activation was investigated with electromobility shift assay. mRNA expression of inflammatory mediators and their corresponding receptors were detected with Ribonuclease Protection Assay. Protein expression was detected by ELISA and western blotting. Inducible NO synthase (iNOS) expression was monitored by RT-PCR and iNOS activity by conversion of l-arginine to citrulline. Immune cells were sampled by bronchoalveolar lavage (BAL) and classified. Results: LPS application induced CD14-, but not TLR4 protein expression in control mice. Activation of pulmonary NFκB was observed within 60 min in control, but not in TLR4-D mice. Six hours of LPS administration induced a significant increase in pulmonary tumour necrosis factor α-, interleukin-1β- and interleukin-6 mRNA and protein expression in control mice compared to TLR4-D mice. Furthermore, LPS induced a significantly higher increase of the iNOS expression and catalytic activity in control mice than in TLR4-D mice. BAL revealed an increase in total cell count in all LPS treated mice. Conclusion: Our findings suggest that TLR4 plays a key role for regulating the expression of relevant cytokines within the lung during endotoxic shock.

Summary

Background and objective: The best place for the electrode of transcutaneous measurement of oxygen tension (tcPO2) and carbon dioxide tension (tcPCO2) during general anaesthesia was investigated in three different locations. Methods: Fifteen patients for major abdominal surgery in the supine position were studied. The electrode of the TCM4™ (Radiometer, Copenhagen, Denmark) was put on the chest, upper arm or forearm. TcPO2, tcPCO2, end-tidal carbon dioxide tension (etCO2), percutaneous oxygen saturation (SaO2), arterial oxygen tension (PaO2 ) and arterial carbon dioxide tension (PaCO2) were simultaneously measured at four different etCO2 concentrations and inhaled oxygen percentages and the location of the electrode was changed to other places to repeat the same measurement. In total, 12 measurements for each patient and 60 measurements for each place were performed. Results: TcPO2 correlated better than SaO2 (R2 = 0.58) with PaO2 (R2 = 0.76), and tcPCO2 correlated well with PaCO2 (R2 = 0.76) and etCO2 (R2 = 0.74) when the electrode was put on the chest, while not on the upper arm or forearm (R2 < 0.5). However, limits of agreement were too big to use tcPO2 (bias, −67.9; limits of agreement, 16.5, −152.3) and tcPCO2 (bias, −0.47; limits of agreement, 8.7, −9.64) as surrogate measures of PaO2 and PaCO2, respectively even when the electrode was put on the chest. Conclusions: When the electrode was put on the chest, tcPO2 and tcPCO2 might be available as non-invasive monitors of oxygenation and CO2 status during general anaesthesia, while the absolute values were not interchangeable with PaO2 and PaCO2, respectively.

Summary

Background: The purpose of this study was to assess whether the addition of intravenous magnesium sulphate (Mg) at the induction of anaesthesia to a balanced anaesthetic protocol including wound infiltration, paracetamol and tramadol resulted in improved analgesic efficiency after radical prostatectomy. Methods: We conducted a randomized, double-blind, controlled study. Thirty ASA I or II males scheduled to undergo radical retropubic prostatectomy with general anaesthesia were prospectively assigned to one of the two groups (n = 15 each). The Mg group (Gr Mg) received 50 mg kg−1 of MgSO4 in 100 mL of isotonic saline over 20 min immediately after induction of anaesthesia and before skin incision. The patients in the control group (Gr C) received the same volume of saline over the same period. At the time of abdominal closure, wound infiltration with 190 mg (40 mL) of ropivacaine was performed in both groups. Pain was assessed by a 10-point visual analogue scale in the recovery room starting from the time of tracheal extubation. Standardized postoperative analgesia included paracetamol and tramadol administered via a patient-controlled analgesia device. Results: In the postoperative period, both groups experienced an identical pain course evolution. Cumulative mean tramadol dose after 24 h was 226 mg in the magnesium group and 446 mg in the control group (P < 0.001). Postoperative nausea occurred in two patients in each group. Two vs. eight patients required analgesic rescue in magnesium and control groups, respectively (P = 0.053). Conclusions: This study shows that intravenous magnesium sulphate reduces tramadol consumption when used as a postoperative analgesic protocol in radical prostatectomy.