Reviewing next of kin regrets in surgical decision-making: cross-sectional analysis of systematically searched literature.

BACKGROUND: Decision-making concerning relatives undergoing surgery is challenging. It remains unclear to what extent implicated next of kin eventually regret their decisions and how this regret is assessed. Our aim was to systematically review the literature on decisional regret of next of kin and to describe the assessment tools used and the surgical populations studied. METHODS: We included interventional or observational, quantitative or qualitative studies reporting the measurement of decisional regret of next of kin concerning relatives undergoing surgery. We searched a variety of databases without restriction on publication year. We assessed the quality of reporting of quantitative studies using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and of qualitative studies using the Critical Appraisal Skills Program Checklist. RESULTS: Thirteen cross-sectional, five prospective cohorts and five qualitative studies matched our inclusion criteria. In 18 studies (78%), patients were children, in five (22%), young or middle-aged adults. No study included elderly or frail patients. Thirteen studies (57%) used the original Decision Regret Scale which was validated for patients, but not for next of kin. Only 3 of the 18 (17%) quantitative studies and only one of the 4 (25%) qualitative studies were rated as "good" in the quality assessment. CONCLUSION: None of the retrieved studies used validated tools to assess the decisional regret of next of kin and none of them examined this issue in elderly or frail surgical patients.

Dexamethasone for the treatment of established postoperative nausea and vomiting: A randomised dose finding trial.

BACKGROUND: Dexamethasone is widely used for the prevention of postoperative nausea and vomiting (PONV) but little is known about its efficacy for the treatment of established PONV. OBJECTIVE: To test the antiemetic efficacy of intravenous dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia and to determine whether there is dose-responsiveness. DESIGN: The DexPonv trial is a multicentre, placebo-controlled, randomised, double-blind, dose-finding study. Inclusion of patients was between September 2012 and November 2017. Follow-up for PONV symptoms was for 24 h. Thirty days postoperatively, patients were contacted by study nurses for any information on postoperative bleeding and infection. SETTING: Four public hospitals in Switzerland. PATIENTS: A total of 803 adults scheduled for elective surgery without any antiemetic prophylaxis signed the consent form; 714 were included. Among those, 319 had PONV and 281 patients were eventually randomised (intention to treat population and safety set). The per protocol set consisted of 260 patients. INTERVENTIONS: Patients with PONV symptoms (including retching) were randomised to a single intravenous dose of dexamethasone 3, 6 or 12 mg or matching placebo. MAIN OUTCOME MEASURES: The primary endpoint was the absence of further nausea or vomiting (including retching), within 24 h after administration of the study drug. RESULTS: Dexamethasone was ineffective during the first 24 h, whatever the dosage, compared to placebo, even when the model was adjusted for known risk factors (P = 0.170). There were no differences in the time to treatment failure or the quality of sleep during the first night. There was a positive correlation between the dose of dexamethasone and blood glucose concentrations (P < 0.001), but not with bleeding risk, wound infections or other adverse effects. CONCLUSION: This randomised trial failed to show anti-emetic efficacy of any of the tested intravenous regimens of dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia. TRIAL REGISTRATION: clinicaltrials.gov (NCT01975727).

Genetic Susceptibility Toward Nausea and Vomiting in Surgical Patients.

Postoperative nausea and vomiting (PONV) are frequently occurring adverse effects following surgical procedures. Despite predictive risk scores and a pallet of prophylactic antiemetic treatments, it is still estimated to affect around 30% of the patients, reducing their well-being and increasing the burden of post-operative care. The aim of the current study was to characterize selected genetic risk factors of PONV to improve the identification of at risk patients. We genotyped 601 patients followed during the first 24 h after surgery for PONV symptoms in the absence of any antiemetic prophylaxis. These patients were recruited in the frame of a randomized, placebo controlled clinical study aiming to test the efficacy of dexamethasone as a treatment of established PONV. We examined the impact of selected single nucleotide polymorphisms (SNPs) located around 13 different genes and the predicted activity of 6 liver drug metabolizing enzymes from the cytochromes P450 family (CYP) on the occurrence and recurrence of PONV. Our genetic study confirms the importance of genetic variations in the type 3B serotonin receptor in the occurrence of PONV. Our modelling shows that integration of rs3782025 genotype in preoperative risk assessments may help improve the targeting of antiemetic prophylaxis towards patients at risk of PONV.

Assessment of spontaneous neuromuscular recovery: A comparison of the TOF-Cuff® with the TOF Watch SX®.

BACKGROUND: TOF-Cuff® is a modified blood pressure cuff used to monitor neuromuscular block. We compared the assessment of spontaneous neuromuscular recovery between TOF-Cuff® (test device) and TOF Watch SX® (reference device). METHODS: Forty patients aged 18-65 years undergoing elective surgery were enrolled. TOF-Cuff® was installed on an upper arm and the TOF Watch SX® on the thumb of the opposite side. Anaesthesia was induced and maintained with intravenous propofol and sufentanil. After induction, the devices were calibrated and continuous train-of-four (TOF) stimulation was started. A single intravenous dose of rocuronium (0.6 mg kg-1 ) was administered for intubation. The primary outcome was total recovery time (time in minutes from the injection of rocuronium to a normalized TOF ratio of 90%). Agreement between the two devices was calculated using mean difference and limits of agreement. RESULTS: The primary outcome could be analysed in 27 patients because of 13 exclusions due to neuromuscular block reversal for shorter procedure surgical time, necessity of reinjection of rocuronium or technical failures of one of the two devices. Median total recovery time with the test device was 45 minutes (interquartile range [IQR] 38.5-61.5) and 63 minutes (IQR 51.1-74.5) with the reference device. Total recovery time with the test device was on average 16.4 minutes shorter (limits of agreement, -6.1 to 39); increasing total recovery time was associated with increasing difference. The TOF ratio of the reference device was on average 0.59 (SD 0.23) when the test device indicated complete recovery. The TOF ratio of the test device was on average 0.98 (SD 0.03) when the reference device indicated complete recovery. CONCLUSION: When compared with the TOF Watch SX® , TOF-Cuff® overestimates spontaneous recovery of a rocuronium-induced neuromuscular block.

Contraction response to muscle percussion: A reappraisal of the mechanism of this bedside test.

OBJECTIVE: To study whether the contraction evoked by muscle percussion stems from the excitation of the muscle or of the nerve and to discuss the changes of this response in neuromuscular disorders. METHODS: In 30 neurologically healthy patients undergoing surgery (for ear, nose, or throat problems unrelated to the study) under general anesthesia with propofol and sufentanil we measured with an electrogoniometer the maximal dorsiflexion of the ankle evoked by reflex hammer percussion of the tibialis anterior muscle before and under neuromuscular junction blockade with rocuronium bromide. In 3 additional healthy volunteers we searched for F-waves to disclose whether percussion excites axons within the muscle. RESULTS: Responses from 28 neurologically healthy patients (15 women) were analyzed after exclusion of 2 due to technical problems. Mean age (SD) was 28 (9) years. Maximal dorsiflexion of the ankle was not significantly modified by neuromuscular junction blockade (mean difference 0.01 mV [95%CI, -0.07 to 0.08], p=0.879). Muscle percussion evoked F-waves in the 3 healthy volunteers tested. CONCLUSIONS: Maximal contraction response to muscle percussion has a muscular rather than a neural origin. However, percussion also excites axons within the muscle. SIGNIFICANCE: These findings may provide clues to understand the changes observed in neuromuscular disorders.

Interventions for treating bisphosphonate-related osteonecrosis of the jaw (BRONJ).

BACKGROUND: Bisphosphonate drugs can be used to prevent and treat osteoporosis and to reduce symptoms and complications of metastatic bone disease; however, they are associated with a rare but serious adverse event: osteonecrosis of the maxillary and mandibular bones. This condition is called bisphosphonate-related osteonecrosis of the jaw or BRONJ. BRONJ is diagnosed when people who are taking, or have previously taken, bisphosphonates have exposed bone in the jaw area for more than eight weeks in the absence of radiation treatment. There is currently no "gold standard" of treatment for BRONJ. The three broad categories of intervention are conservative approaches (e.g. mouth rinse, antibiotics), surgical interventions and adjuvant non-surgical strategies (e.g. hyperbaric oxygen therapy, platelet-rich plasma), which can be used in combination. OBJECTIVES: To determine the efficacy and safety of any intervention aimed at treating BRONJ. SEARCH METHODS: We searched the following databases to 15 December 2015: the Cochrane Oral Health Group Trials Register, the Cochrane Breast Cancer Group Trials Register (20 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, EMBASE via Ovid, CancerLit via PubMed, CINAHL via EBSCO and AMED via Ovid. We scanned the references cited in retrieved articles and contacted experts in the field, the first authors of included papers, study sponsors, other bisphosphonates investigators and pharmaceutical companies. We searched for ongoing trials through contact with trialists and by searching the US National Institutes of Health Trials Register (clinicaltrials.gov) and the World Health Organization Clinical Trials Registry Platform. We also conducted a grey literature search to September 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effects of any treatment for BRONJ with another treatment or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed the risk of bias in the included trials and extracted data. When in dispute, we consulted a third review author. MAIN RESULTS: One small trial at high risk of bias met the inclusion criteria. The trial randomised 49 participants, most of whom had cancer. It compared standard care (defined as surgery, antibiotics and oral rinses at the discretion of the oral-maxillofacial surgeon) to standard care plus hyperbaric oxygen therapy (2 atmospheres twice a day for 40 treatments). The trial measured the percentage of participants who improved or healed at three, six, 12 and 18 months and last contact. It also measured mean weekly pain scores.At three months, the study found that the participants in intervention group were more likely to have an improvement in their osteonecrosis than the standard care group participants (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.01 to 3.74). There was no clear difference between the groups for the outcome 'healed' at three months (RR 3.60, 95% CI 0.87 to 14.82). There was no clear difference between the groups for improvement or healing when they were evaluated at six, 12 and 18 months and last contact.The study did not give any information on adverse events.Although the findings suggest adjunctive hyperbaric oxygen improved BRONJ, the quality of the evidence is very low since the only study was underpowered and was at high risk of bias due to lack of blinding, cross-over of participants between groups and very high attrition (50% at 12 months and 80% at 18 months in this study, which was designed for an intended follow-up of 24 months). AUTHORS' CONCLUSIONS: There is a lack of evidence from randomised controlled trials to guide treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ). One small trial at high risk of bias evaluated hyperbaric oxygen therapy (HBO) as an adjunct to "standard" care and could not confirm or refute the effectiveness of HBO. There are two ongoing trials of teriparatide treatment for BRONJ. We found no randomised controlled trials of any other BRONJ treatments. High quality randomised controlled trials are needed. We provide recommendations for their focus and design.

Erythromycin for Gastric Emptying in Patients Undergoing General Anesthesia for Emergency Surgery: A Randomized Clinical Trial.

IMPORTANCE: Patients undergoing emergency procedures under general anesthesia have impaired gastric emptying and are at high risk for aspiration of gastric contents. Erythromycin has strong gastric prokinetic properties. OBJECTIVE: To evaluate the efficacy of erythromycin lactobionate in gastric emptying in patients undergoing emergency surgery. DESIGN, SETTING, AND PARTICIPANTS: The Erythro-Emerge trial was a single-center, randomized, double-blinded, placebo-controlled clinical trial in patients undergoing emergency surgery under general anesthesia at Geneva University Hospitals. We included 132 patients from March 25, 2009, through April 10, 2013, and all patients completed the study. Randomization was stratified for trauma and nontrauma procedures. The randomization code was opened on April 23, 2013, and analyses were performed through July 26, 2013. We performed an intention-to-treat analysis. INTERVENTIONS: Patients were randomized to intravenous erythromycin lactobionate, 3 mg/kg, or placebo 15 minutes before tracheal intubation. Patients were followed up for 24 hours. MAIN OUTCOMES AND MEASURES: The primary outcome was a clear stomach, defined as less than 40 mL of liquids and no solids and identified through endoscopy immediately after intubation. The secondary outcome was the pH level of residual gastric content. RESULTS: A clear stomach was diagnosed in 42 of 66 patients (64%) receiving placebo compared with 53 of 66 patients (80%) receiving erythromycin (risk ratio, 1.26 [95% CI, 1.01-1.57]). In the population undergoing surgery for nontrauma, the association between receipt of erythromycin and having a clear stomach (adjusted odds ratio [95% CI]) was statistically significant (13.4 [1.49-120]; P = .02); in the population undergoing surgery for trauma, it was not (1.81 [0.64-5.16]; P = .26). Median (interquartile range) pH of the residual gastric liquid was 2 (1-4) in 36 patients receiving placebo and 6 (3-7) in 16 receiving erythromycin (P = .002). Patients receiving erythromycin had nausea (20 [30%] vs 4 [6%]) and stomach cramps (15 [23%] vs 2 [3%]) more often than those receiving placebo. One patient receiving erythromycin vomited before induction of anesthesia. CONCLUSIONS AND RELEVANCE: In patients undergoing general anesthesia for emergency procedures, erythromycin administration increased the proportion with a clear stomach and decreased the acidity of residual gastric liquid. Erythromycin was particularly efficacious in the nontrauma population. Adverse effects were minor. Further large-scale studies are warranted to confirm the potential of erythromycin to reduce the incidence of bronchoaspiration in patients undergoing emergency surgery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00827216.

Consensus guidelines for the management of postoperative nausea and vomiting.

The present guidelines are the most recent data on postoperative nausea and vomiting (PONV) and an update on the 2 previous sets of guidelines published in 2003 and 2007. These guidelines were compiled by a multidisciplinary international panel of individuals with interest and expertise in PONV under the auspices of the Society for Ambulatory Anesthesia. The panel members critically and systematically evaluated the current medical literature on PONV to provide an evidence-based reference tool for the management of adults and children who are undergoing surgery and are at increased risk for PONV. These guidelines identify patients at risk for PONV in adults and children; recommend approaches for reducing baseline risks for PONV; identify the most effective antiemetic single therapy and combination therapy regimens for PONV prophylaxis, including nonpharmacologic approaches; recommend strategies for treatment of PONV when it occurs; provide an algorithm for the management of individuals at increased risk for PONV as well as steps to ensure PONV prevention and treatment are implemented in the clinical setting.

Impact of epidural analgesia on mortality and morbidity after surgery: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To quantify benefit and harm of epidural analgesia, compared with systemic opioid analgesia, in adults having surgery under general anesthesia. BACKGROUND: It remains controversial whether adding epidural analgesia to general anesthesia decreases postoperative morbidity and mortality. METHODS: We searched CENTRAL, EMBASE, PubMed, CINAHL, and BIOSIS till July 2012. We included randomized controlled trials comparing epidural analgesia (with local anesthetics, lasting for ≥ 24 hours postoperatively) with systemic analgesia in adults having surgery under general anesthesia, and reporting on mortality or any morbidity endpoint. RESULTS: A total of 125 trials (9044 patients, 4525 received epidural analgesia) were eligible. In 10 trials (2201 patients; 87 deaths), reporting on mortality as a primary or secondary endpoint, the risk of death was decreased with epidural analgesia (3.1% vs 4.9%; odds ratio, 0.60; 95% confidence interval, 0.39-0.93). Epidural analgesia significantly decreased the risk of atrial fibrillation, supraventricular tachycardia, deep vein thrombosis, respiratory depression, atelectasis, pneumonia, ileus, and postoperative nausea and vomiting, and also improved recovery of bowel function, but significantly increased the risk of arterial hypotension, pruritus, urinary retention, and motor blockade. Technical failures occurred in 6.1% of patients. CONCLUSIONS: In adults having surgery under general anesthesia, concomitant epidural analgesia reduces postoperative mortality and improves a multitude of cardiovascular, respiratory, and gastrointestinal morbidity endpoints compared with patients receiving systemic analgesia. Because adverse effects and technical failures cannot be ruled out, individual risk-benefit analyses and professional care are recommended.

Combination of a reduced dose of an intrathecal local anesthetic with a small dose of an opioid: a meta-analysis of randomized trials.

We tested whether the combination of a reduced dose of a local anesthetic (LA) with an opioid compared with a standard dose of the same LA alone guaranteed adequate intraoperative anesthesia and postoperative analgesia and decreased LA-related adverse effects. We systematically searched (to November 2012) for randomized comparisons of combinations of a reduced dose of an LA with a concomitant opioid (experimental) with a standard dose of the LA alone (control) in adults undergoing surgery with single-injection intrathecal anesthesia without general anesthesia. We included 28 trials (1393 patients). In experimental groups, the median decrease in LA doses was 40% (range, 12%-70%). There was no difference between experimental and control groups in the need for intraoperative opioids or general anesthesia for failed block or in the duration of postoperative analgesia. With experimental interventions, there was evidence of a reduction in the duration of motor blockade postoperatively (average, -50 minutes), time to discharge from hospital or PACU (-33 minutes), time to ambulation (-28 minutes), and time to urination (-14 minutes). There was also evidence of a decrease in the risk of shivering (risk ratio [RR]: 0.26; 95% confidence interval [CI]: 0.12-0.56), nausea (RR: 0.45; 95% CI: 0.31-0.66), and arterial hypotension (RR: 0.52; 95% CI: 0.35-0.78). The risk of pruritus was increased (RR: 11.7; 95% CI: 6.2-21.9). Adding an opioid to a reduced dose of an intrathecal LA can decrease LA-related adverse effects and improve recovery from the spinal block without compromising intraoperative anesthesia or duration of postoperative analgesia.

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.

Intravenous buspirone for the prevention of postoperative nausea and vomiting.

RATIONALE: Buspirone, a partial 5HT(1A) agonist and D2 and D3 antagonist, has shown promising antiemetic efficacy when given parenterally in animal models, but its efficacy for the prevention of postoperative nausea and vomiting (PONV) is unknown. OBJECTIVE: To study the efficacy and dose-responsiveness of intravenous buspirone for the prevention of PONV. METHODS: A randomised, double-blind, placebo-controlled study was performed in adults at moderate to high PONV risk undergoing surgery with a general anaesthetic. Patients were randomised to receive an intravenous dose of buspirone (0.3, 1.0, 2.0, 3.0 mg) or placebo at the end of surgery. The primary endpoint was the cumulative 24-h PONV incidence (i.e. any nausea and/or vomiting). Vomiting included retching. Nausea was defined as a score of ≥ 4 on an 11-point verbal rating scale running from zero (no nausea) to ten (the worst nausea imaginable). RESULTS: A total of 257 patients received the study drug and fulfilled the criteria for inclusion in the primary efficacy and safety analyses. With placebo, the mean 24-h PONV incidence was 49.0 % (90 % confidence interval [CI] 37.5-60.5 %). With buspirone, that incidence ranged from a mean of 40.8 % (29.3-52.4 %) in the 1 mg arm to 58.0 % (46.5-69.5 %) in the 0.3 mg arm (P > 0.05 for all comparisons). There was no difference between placebo and buspirone at any dose for any other efficacy endpoint, nor in the number or severity of adverse events or any other safety measures. CONCLUSION: We were unable to show that intravenous single-dose buspirone, at the tested dose-range, was effective at preventing PONV in surgical adult patients. The present study emphasises the difficulty in extrapolating from animal models of emesis to clinical efficacy in PONV.

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

BACKGROUND: Systemic α2 agonists are believed to reduce pain and opioid requirements after surgery, thus decreasing the incidence of opioid-related adverse effects, including hyperalgesia. METHODS: The authors searched for randomized placebo-controlled trials testing systemic α2 agonists administrated in surgical patients and reporting on postoperative cumulative opioid consumption and/or pain intensity. Meta-analyses were performed when data from 5 or more trials and/or 100 or more patients could be combined. RESULTS: Thirty studies (1,792 patients, 933 received clonidine or dexmedetomidine) were included. There was evidence of postoperative morphine-sparing at 24 h; the weighted mean difference was -4.1 mg (95% confidence interval, -6.0 to -2.2) with clonidine and -14.5 mg (-22.1 to -6.8) with dexmedetomidine. There was also evidence of a decrease in pain intensity at 24 h; the weighted mean difference was -0.7 cm (-1.2 to -0.1) on a 10-cm visual analog scale with clonidine and -0.6 cm (-0.9 to -0.2) with dexmedetomidine. The incidence of early nausea was decreased with both (number needed to treat, approximately nine). Clonidine increased the risk of intraoperative (number needed to harm, approximately nine) and postoperative hypotension (number needed to harm, 20). Dexmedetomidine increased the risk of postoperative bradycardia (number needed to harm, three). Recovery times were not prolonged. No trial reported on chronic pain or hyperalgesia. CONCLUSIONS: Perioperative systemic α2 agonists decrease postoperative opioid consumption, pain intensity, and nausea. Recovery times are not prolonged. Common adverse effects are bradycardia and arterial hypotension. The impact of α2 agonists on chronic pain or hyperalgesia remains unclear because valid data are lacking.

Opioids added to local anesthetics for single-shot intrathecal anesthesia in patients undergoing minor surgery: a meta-analysis of randomized trials.

Opioids are widely used as additives to local anesthetics for intrathecal anesthesia. Benefit and risk remain unclear. We systematically searched databases and bibliographies to February 2011 for full reports of randomized comparisons of any opioid added to any intrathecal local anesthetic with the local anesthetic alone in adults undergoing surgery (except cesarean section) and receiving single-shot intrathecal anesthesia without general anesthesia. We included 65 trials (3338 patients, 1932 of whom received opioids) published between 1983 and 2010. Morphine (0.05-2mg) and fentanyl (10-50 µg) added to bupivacaine were the most frequently tested. Duration of postoperative analgesia was prolonged with morphine (weighted mean difference 503 min; 95% confidence interval [CI] 315 to 641) and fentanyl (weighted mean difference 114 min; 95% CI 60 to 168). Morphine decreased the number of patients needing opioid analgesia after surgery and decreased pain intensity to the 12th postoperative hour. Morphine increased the risk of nausea (number needed to harm [NNH] 9.9), vomiting (NNH 10), urinary retention (NNH 6.5), and pruritus (NNH 4.4). Fentanyl increased the risk of pruritus (NNH 3.3). With morphine 0.05 to 0.5mg, the NNH for respiratory depression varied between 38 and 59 depending on the definition of respiratory depression chosen. With fentanyl 10 to 40 µg, the risk of respiratory depression was not significantly increased. For none of these effects, beneficial or harmful, was there evidence of dose-responsiveness. Consequently, minimal effective doses of intrathecal morphine and fentanyl should be sought. For intrathecal buprenorphine, diamorphine, hydromorphone, meperidine, methadone, pentazocine, sufentanil, and tramadol, there were not enough data to allow for meaningful conclusions.

Transcutaneous nicotine does not prevent postoperative nausea and vomiting: a randomized controlled trial.

AIMS: There is empirical evidence that smokers are less likely to suffer from postoperative nausea and vomiting (PONV). We sought to investigate whether transcutaneus nicotine prevents PONV. METHODS: Non-smokers receiving general anaesthesia for surgery were randomly allocated to Nicotinell Patch 10cm(2) (TTS 10), containing 17.5mg of nicotine (average delivery rate, 7mg 24h(-1) ) or matching placebo patch. Patches were applied 1h before surgery and were left in situ until 24h after surgery (or until the first PONV symptoms occurred). RESULTS: We randomized 90 patients (45 nicotine, 45 placebo). In the post-anaesthetic care unit, the incidence of nausea was 22.2% with nicotine and 24.4% with placebo (P= 0.80), and the incidence of vomiting was 20.0% with nicotine and 17.8% with placebo (P= 0.78). Cumulative 24h incidence of nausea was 42.2% with nicotine and 40.0% with placebo (P= 0.83), and of vomiting was 31.1% with nicotine and 28.9% with placebo (P= 0.81). PONV episodes tended to occur earlier in the nicotine group. Postoperative headache occurred in 17.8% of patients treated with nicotine and in 15.6% with placebo (P= 0.49). More patients receiving nicotine reported a low quality of sleep during the first postoperative night (26.7% vs. 6.8% with placebo; P= 0.01). CONCLUSIONS: Non-smokers receiving a prophylactic nicotine patch had a similar incidence of PONV during the first 24h and tended to develop PONV symptoms earlier compared with controls. They had a significantly increased risk of insomnia during the first postoperative night.

Clonidine as an adjuvant to local anesthetics for peripheral nerve and plexus blocks: a meta-analysis of randomized trials.

The effect of adding clonidine to local anesthetics for nerve or plexus blocks remains unclear. The authors searched for randomized placebo-controlled trials testing the impact of adding clonidine to local anesthetics for peripheral single-injection nerve or plexus blocks in adults undergoing any surgery (except eye) without general anesthesia. Twenty trials (1,054 patients, 573 received clonidine) published 1992-2006 tested plexus (14 brachial, 1 cervical) and nerve blocks (2 sciatic/femoral, 1 midhumeral, 1 ilioinguinal/iliohypogastric, 1 ankle). Clonidine doses ranged from 30 to 300 microg; most patients received 150 microg. Clonidine prolonged the duration of postoperative analgesia (weighted mean difference 122 min; 95% confidence interval [CI] 74-169), sensory block (weighted mean difference 74 min; 95% CI 37-111), and motor block (weighted mean difference 141 min; 95% CI 82-199). In a subgroup of patients receiving an axillary plexus block, these effects were independent of whether clonidine was added to an intermediate or a long-acting local anesthetic. Clonidine increased the risk of arterial hypotension (odds ratio 3.61; 95% CI 1.52-8.55; number-needed-to-harm 11), orthostatic hypotension or fainting (odds ratio 5.07; 95% CI 1.20-21.4; number-needed-to-harm 10), bradycardia (odds ratio 3.09; 95% CI 1.10-8.64; number-needed-to-harm 13), and sedation (odds ratio 2.28; 95% CI 1.15-4.51; number-needed-to-harm 5). There was a lack of evidence of dose-responsiveness for beneficial or harmful effects. Clonidine added to intermediate or long-acting local anesthetics for single-shot peripheral nerve or plexus blocks prolongs duration of analgesia and motor block by about 2 h. The increased risk of hypotension, fainting, and sedation may limit its usefulness. Dose-responsiveness remains unclear.

Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery: a meta-analysis.

OBJECTIVE: To review the impact of epidural vs systemic analgesia on postoperative pulmonary complications. DATA SOURCES: Search of databases (1966 to March 2006) and bibliographies. STUDY SELECTION: Inclusion criteria were randomized comparison of epidural vs systemic analgesia lasting 24 hours or longer postoperatively and reporting of pulmonary complications, lung function, or gas exchange. Fifty-eight trials (5904 patients) were included. DATA EXTRACTION: Articles were reviewed and data extracted. Data were combined using fixed-effect and random-effects models. DATA SYNTHESIS: The odds of pneumonia were decreased with epidural analgesia (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.43-0.68), independent of site of surgery or catheter insertion, duration of analgesia, or regimen. The effect was weaker in trials that used patient-controlled analgesia in controls (OR, 0.64; 95% CI, 0.49-0.83) compared with trials that did not (OR, 0.30; 95% CI, 0.18-0.49) and in larger studies (OR, 0.62; 95% CI, 0.47-0.81) compared with smaller studies (OR, 0.37; 95% CI, 0.23-0.58). From 1971-2006, the incidence of pneumonia with epidural analgesia remained about 8% but decreased from 34% to 12% with systemic analgesia (P < .001); consequently, the relative benefit of epidural analgesia decreased also. Epidural analgesia reduced the need for prolonged ventilation or reintubation, improved lung function and blood oxygenation, and increased the risk of hypotension, urinary retention, and pruritus. Technical failures occurred in 7%. CONCLUSION: Epidural analgesia protects against pneumonia following abdominal or thoracic surgery, although this beneficial effect has lessened over the last 35 years because of a decrease in the baseline risk.

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), 15 min after induction but before start of surgery, at skin closure, in the post-anesthetic care unit, and 24 h 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) pg ml(-1) in the propofol group and were 549 +/- 512 pg ml(-1) in the thiopental-isoflurane group (P = 0.31). At 15 min, concentrations significantly decreased in the propofol group (247 +/- 219 pg ml(-1), P = 0.0012 compared with baseline) but remained unchanged in the thiopental-isoflurane group (597 +/- 471 pg ml(-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 24 h, concentrations significantly decreased below baseline in both groups (propofol: 232 +/- 129 pg ml(-1), P = 0.0015; thiopental-isoflurane: 253 +/- 250 pg ml(-1), P = 0.016). In the propofol group, there was a weak but statistically significant positive correlation (R2 = 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 surgery.

Clonidine as an adjuvant to intrathecal local anesthetics for surgery: systematic review of randomized trials.

BACKGROUND AND OBJECTIVES: Clonidine is added to intrathecal local anesthetics to improve intraoperative analgesia and to increase the duration of sensory and motor block. The aim of this systematic review is to quantify beneficial and harmful effects of clonidine when used as an adjuvant to intrathecal local anesthetics for surgery. METHODS: We included data from 22 randomized trials (1,445 patients) testing a large variety of doses of clonidine, added to intrathecal bupivacaine, mepivacaine, prilocaine, or tetracaine. RESULTS: Clonidine 15 to 150 microg prolonged in a linear, dose-dependent manner, the time to 2 segment regression (range of means, 14 to 75 minutes) and the time to regression to L2 (range of means, 11 to 128 minutes). The time to first analgesic request (median 101 minutes, range 35 to 310) and of motor block (median 47 minutes, range 6 to 131) was prolonged without evidence of dose-responsiveness. Time to achieve complete sensory or motor block, and extent of cephalic spread remained unchanged. There were fewer episodes of intraoperative pain with clonidine (relative risk, 0.24; 95% confidence interval [CI], 0.09-0.64; number needed to treat, 13) but more episodes of arterial hypotension (relative risk, 1.81; 95% CI 1.44-2.28; number needed to harm, 8) without evidence of dose-responsiveness. The risk of bradycardia was unchanged. CONCLUSIONS: This study may serve as a rational basis to help clinicians decide whether or not to combine clonidine with an intrathecal local anesthetic for surgery. The optimal dose of clonidine, however, remains unknown.