Plasma Concentrations of Brain-derived Neurotrophic Factor in Patients Undergoing Minor Surgery: A Randomized Controlled Trial

We measured perioperative plasma concentrations of brain-derived neurotrophic factor (BDNF), a major mediator of synaptic plasticity in the central nervous system, in males, 30-65 years old, undergoing lumbar or cervical discotomy. Patients were randomly allocated to a general anesthetic with propofol induction and maintenance or with thiopental induction and isoflurane maintenance. BDNF plasma concentrations were measured before induction (baseline), 15min after induction but before start of surgery, at skin closure, in the post-anesthetic care unit, and 24h postoperatively. Data from 26 patients (13 in each group) were analyzed. At each time point, BDNF plasma concentrations showed large variability. At baseline, concentrations were 631±337 (mean±SD)pgml−1 in the propofol group and were 549±512pgml−1 in the thiopental-isoflurane group (P=0.31). At 15min, concentrations significantly decreased in the propofol group (247±219pgml−1, P=0.0012 compared with baseline) but remained unchanged in the thiopental-isoflurane group (597±471pgml−1, P=0.798 compared with baseline). At skin closure and in the post-anesthetic care unit, concentrations were not different from baseline in both groups. At 24h, concentrations significantly decreased below baseline in both groups (propofol: 232±129pgml−1, P=0.0015; thiopental-isoflurane: 253±250pgml−1, P=0.016). In the propofol group, there was a weak but statistically significant positive correlation (R 2=0.38, P=0.026) between the duration of surgery and BDNF plasma concentrations at skin closure. These data suggest that in males undergoing elective minor surgery, BDNF plasma concentrations show a specific pattern that is influenced by the anesthetic technique and, possibly, by the duration of surger

Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patientcontrolled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials

The authors analyzed data from 52 randomized placebocontrolled trials (4,893 adults) testing acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors given in conjunction with morphine after surgery. The median of the average 24-h morphine consumption in controls was 49 mg (range, 15-117 mg); it was significantly decreased with all regimens by 15-55%. There was evidence of a reduction in pain intensity at 24 h (1 cm on the 0-to 10-cm visual analog scale) only with nonsteroidal antiinflammatory drugs. Nonsteroidal antiinflammatory drugs also significantly reduced the incidence of nausea/vomiting from 28.8% to 22.0% (number needed to treat, 15) and of sedation from 15.4% to 12.7% (number needed to treat, 37) but increased the risk of severe bleeding from 0% to 1.7% (number needed to harm, 59). Selective cyclooxygenase-2 inhibitors increased the risk of renal failure in cardiac patients from 0% to 1.4% (number needed to harm, 73). A decrease in morphine consumption is not a good indicator of the usefulness of a supplemental analgesic. There is evidence that the combination of nonsteroidal antiinflammatory drugs with patient-controlled analgesia morphine offers some advantages over morphine alone

Simplified EEG monitors in anaesthesia. Clinical utility and limitations

Background: An achievement of modern anaesthesia is the ability to monitor its depth. Various methods have been described. More than 150 years ago, Snow and Guedel defined four stages of ether anaesthesia based on somatic muscle tone, respiratory parameters and ocular signs. Unfortunately, this method does not satisfy the objectives of modern anaesthesia with the presence of new anaesthetic drugs, complex and combined anaesthesia techniques, and increasingly older and sicker patients. During the last 15 years, more sophisticated depths of anaesthesia monitors have become available. These are based on electroencephalogram (EEG) or auditory-evoked potentials (AEPs). Both EEG and AEP transform biological signals that are related to changes in brain activity observed during anaesthesia. BIS and Spectral Entropy, both based on the EEG, were among the first commercialised depths of anaesthesia monitors. Sophisticated algorithms were used to express modifications of the EEG that are related to changes in brain status during anaesthesia. Some of these algorithms are accessible to a large public; some of them are kept secret. It was claimed that numerical scales recommended for adequate depth of anaesthesia were independent of anaesthetic drugs and patients' age. Knowing that primo: anaesthetic agents have different sites of action and diverse impacts on brain activity, and secondo: EEG patterns change with increasing age, it seems justified to investigate the influence of these factors on clinical utility of simplified EEG monitors. The aim of this work was to address these issues. Methods: Three studies were performed in which the influence of co-administration of opioids, chronic nicotine intake and increasing age on indices of BIS and Spectral Entropy were investigated. In these studies hypnotic component of anaesthesia was assured by strictly controlled administration of propofol. Sedation status, including loss of consciousness, was clinically evaluated using Observer's Assessment of Alertness/Sedation Scale. Indices of EEG monitors at loss of consciousness were recorded. Results: In the first study we observed that in the presence of an opioid loss of consciousness occurred in significantly higher BIS values and lower propofol concentration compared with placebo. In the second trial significantly higher values of BIS at baseline, at 0.7 g.ml-1 and 1.1 g.ml-1 propofol concentrations were found in smokers as compared with no-smokers, furthermore smokers lost consciousness at lower BIS values and higher propofol concentrations. In the third study loss of consciousness indices of BIS and Spectral Entropy were significantly higher in elderly ( 65yr) compared with young ( 40yr) patients. With all these monitors only a minority of elderly patients lost consciousness within recommended safety limits. Implications: All three investigated factors; opioid, chronic nicotine intake and increasing age influenced indices of simplified EEG monitors. Although clinically the hypnotic effect of propofol is enhanced by analgesic concentrations of -agonist opioids, the BIS does not show this increased hypnotic effect. Moreover the correlation between hypnotic effect of propofol and BIS is influenced by chronic nicotine intake. In adults undergoing propofol induction BIS, state entropy and response entropy at loss of consciousness are significantly affected by age. Further studies are needed to investigate the impact of these factors on EEG indices during general anaesthesia, but in our opinion they should be taken into account in the calculation of new software versions of these monitors

Nefopam for the prevention of postoperative pain: quantitative systematic review

Nefopam, a centrally acting analgesic, has been used in the surgical setting in many countries since the mid-1970s. However, clinical trials provide contflicting results for its analgesic potency. We performed a systematic search (multiple databases, bibliographies, any language, to January 2008) for randomized, placebo-controlled trials of nefopam for the prevention of postoperative pain. Data were combined using classic methods of meta-analyses and were expressed as weighted mean difference (WMD), relative risk (RR), and number needed to treat/harm (NNT/H) with 95% confidence interval (CI). Nine trials (847 adult patients, 359 received nefopam) were included. Nefopam (cumulative doses, 20-160 mg) was given orally or i.v., as single or multiple doses, or as a continuous infusion. Compared with placebo, cumulative 24 h morphine consumption was decreased with nefopam: WMD -13 mg (95% CI -17.9 to -8.15). Pain intensity at 24 h was also decreased: on a 100 mm visual analogue scale, WMD -11.5 mm (95% CI -15.1 to -7.85). The incidence of tachycardia was increased with nefopam (RR 3.12, 95% CI 1.11-8.79; NNH 7), as was the incidence of sweating (RR 4.92, 95% CI 2.0-12.1; NNH 13). There is limited evidence from the published literature that nefopam may be a useful non-opioid analgesic in surgical patients. The analgesic potency seems to be similar to non-steroidal anti-inflammatory drugs. However, dose responsiveness and adverse effect profile remain unclear, and the role of nefopam as part of multimodal analgesia needs to be established. Data in children are lacking

Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: meta-analysis of randomized trials

Intrathecal morphine without local anaesthetic is often added to a general anaesthetic to prevent pain after major surgery. Quantification of benefit and harm and assessment of dose-response are needed. We performed a meta-analysis of randomized trials testing intrathecal morphine alone (without local anaesthetic) in adults undergoing major surgery under general anaesthesia. Twenty-seven studies (15 cardiac-thoracic, nine abdominal, and three spine surgery) were included; 645 patients received intrathecal morphine (dose-range, 100-4000 microg). Pain intensity at rest was decreased by 2 cm on the 10 cm visual analogue scale up to 4 h after operation and by about 1 cm at 12 and 24 h. Pain intensity on movement was decreased by 2 cm at 12 and 24 h. Opioid requirement was decreased intraoperatively, and up to 48 h after operation. Morphine-sparing at 24 h was significantly greater after abdominal surgery {weighted mean difference, -24.2 mg [95% confidence interval (CI) -29.5 to -19.0]}, compared with cardiac-thoracic surgery [-9.7 mg (95% CI -17.6 to -1.80)]. The incidence of respiratory depression was increased with intrathecal morphine [odds ratio (OR) 7.86 (95% CI 1.54-40.3)], as was the incidence of pruritus [OR 3.85 (95% CI 2.40-6.15)]. There was no evidence of linear dose-responsiveness for any of the beneficial or harmful outcomes. In conclusion, intrathecal morphine decreases pain intensity at rest and on movement up to 24 h after major surgery. Morphine-sparing is more pronounced after abdominal than after cardiac-thoracic surgery. Respiratory depression remains a major safety concern

Low-dose droperidol (≤1 mg or ≤15 μg kg-1) for the prevention of postoperative nausea and vomiting in adults: quantitative systematic review of randomised controlled trials

Droperidol is widely used for the prevention of postoperative nausea and vomiting (PONV) in European countries. It is unclear how efficacious low-dose droperidol is in the prevention of PONV

Intravenous lidocaine has no impact on rocuronium-induced neuromuscular block. Randomised study

Intravenous lidocaine is increasingly used in surgical patients. As it has neuromuscular blocking effects, we tested the impact of an intravenous lidocaine infusion on the time course of a rocuronium-induced neuromuscular block

Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials

Systemic α2 agonists are believed to reduce pain and opioid requirements after surgery, thus decreasing the incidence of opioid-related adverse effects, including hyperalgesia

Time course of rocuronium-induced neuromuscular block after pre-treatment with magnesium sulphate: a randomised study

BACKGROUND: A previously published study suggested that pre-treatment with magnesium sulphate (MgSO(4)) had no impact on the speed of onset of rocuronium-induced neuromuscular block. We set out to verify this assumption. METHODS: Eighty patients (18-60 years) were randomly allocated to MgSO(4) 60 mg/kg or placebo (saline). Study drugs were given intravenously for 15 min before induction of anaesthesia with propofol, sufentanil and rocuronium 0.6 mg/kg. Anaesthesia was maintained with a target-controlled propofol infusion. Neuromuscular transmission was measured using train-of-four (TOF)-Watch SX acceleromyography. RESULTS: Onset was analysed in 37 MgSO(4) and 38 saline patients, and recovery in 35 MgSO(4) and 37 saline patients. Onset time (to 95% depression of T1) was on average 77 [SD=18] s with MgSO(4) and 120 [48] s with saline (P<0.001). The total recovery time (DurTOF0.9) was on average 73.2 [22] min with MgSO(4) and 57.8 [14.2] min with saline (P<0.003). The clinical duration (Dur25%) was on average 44.7 [14] min with MgSO(4) and 33.2 [8.1] min with saline (P<0.0002). The recovery index (Dur25-75%) was on average 14.0 [6] min with MgSO(4) and 11.2 [5.2] min with saline (P<0.02). The recovery time (Dur25%TOF0.9) was on average 28.5 [11.7] min with MgSO(4) and 24.7 [8.4] min with saline (P=0.28). CONCLUSION: Magnesium sulphate given 15 min before propofol anaesthesia reduces the onset time of rocuronium by about 35% and prolongs the total recovery time by about 25%

Effect of intraoperative high inspired oxygen fraction on surgical site infection, postoperative nausea and vomiting, and pulmonary function: Systematic review and meta-analysis of randomized controlled trials

BACKGROUND:: Intraoperative high inspired oxygen fraction (FIO2) is thought to reduce the incidence of surgical site infection (SSI) and postoperative nausea and vomiting, and to promote postoperative atelectasis. METHODS:: The authors searched for randomized trials (till September 2012) comparing intraoperative high with normal FIO2 in adults undergoing surgery with general anesthesia and reporting on SSI, nausea or vomiting, or pulmonary outcomes. RESULTS:: The authors included 22 trials (7,001 patients) published in 26 reports. High FIO2 ranged from 80 to 100% (median, 80%); normal FIO2 ranged from 30 to 40% (median, 30%). In nine trials (5,103 patients, most received prophylactic antibiotics), the incidence of SSI decreased from 14.1% with normal FIO2 to 11.4% with high FIO2; risk ratio, 0.77 (95% CI, 0.59-1.00). After colorectal surgery, the incidence of SSI decreased from 19.3 to 15.2%; risk ratio, 0.78 (95% CI, 0.60-1.02). In 11 trials (2,293 patients), the incidence of nausea decreased from 24.8% with normal FIO2 to 19.5% with high FIO2; risk ratio, 0.79 (95% CI, 0.66-0.93). In patients receiving inhalational anesthetics without prophylactic antiemetics, high FIO2 provided a significant protective effect against both nausea and vomiting. Nine trials (3,698 patients) reported on pulmonary outcomes. The risk of atelectasis was not increased with high FIO2. CONCLUSIONS:: Intraoperative high FIO2 further decreases the risk of SSI in surgical patients receiving prophylactic antibiotics, has a weak beneficial effect on nausea, and does not increase the risk of postoperative atelectasis