Nadia Elia

Does Multimodal Analgesia with Acetaminophen, Nonsteroidal Antiinflammatory Drugs, or Selective Cyclooxygenase-2 Inhibitors and Patient-controlled Analgesia Morphine Offer Advantages over Morphine Alone?Meta-analyses of Randomized Trials

The authors analyzed data from 52 randomized placebo-controlled 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.

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.

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

Background: Systemic &agr;2 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 &agr;2 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 &agr;2 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 &agr;2 agonists on chronic pain or hyperalgesia remains unclear because valid data are lacking.

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.

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 μg; most patients received 150 μg. 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.

Dexamethasone and Risk of Nausea and Vomiting and Postoperative Bleeding After Tonsillectomy in Children: A Randomized Trial

CONTEXT Dexamethasone is widely used to prevent postoperative nausea and vomiting (PONV) in pediatric tonsillectomy. OBJECTIVE To assess whether dexamethasone dose-dependently reduces the risk of PONV at 24 hours after tonsillectomy. DESIGN, SETTING, AND PATIENTS Randomized placebo-controlled trial conducted among 215 children undergoing elective tonsillectomy at a major public teaching hospital in Switzerland from February 2005 to December 2007. INTERVENTIONS Children were randomly assigned to receive dexamethasone (0.05, 0.15, or 0.5 mg/kg) or placebo intravenously after induction of anesthesia. Acetaminophen-codeine and ibuprofen were given as postoperative analgesia. Follow-up continued until the 10th postoperative day. MAIN OUTCOME MEASURES The primary end point was prevention of PONV at 24 hours; secondary end points were decrease in the need for ibuprofen at 24 hours and evaluation of adverse effects. RESULTS At 24 hours, 24 of 54 participants who received placebo (44%; 95% confidence interval [CI], 31%-59%) had experienced PONV compared with 20 of 53 (38%; 95% CI, 25%-52%), 13 of 54 (24%; 95% CI, 13%-38%), and 6 of 52 (12%; 95% CI, 4%-23%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P<.001 for linear trend). Children who received dexamethasone received significantly less ibuprofen. There were 26 postoperative bleeding episodes in 22 children. Two of 53 (4%; 95% CI, 0.5%-13%) children who received placebo had bleeding compared with 6 of 53 (11%; 95% CI, 4%-23%), 2 of 51 (4%; 95% CI, 0.5%-13%), and 12 of 50 (24%; 95% CI, 13%-38%) who received dexamethasone at 0.05, 0.15, and 0.5 mg/kg, respectively (P = .003). Dexamethasone, 0.5 mg/kg, was associated with the highest bleeding risk (adjusted relative risk, 6.80; 95% CI, 1.77-16.5). Eight children had to undergo emergency reoperation because of bleeding, all of whom had received dexamethasone. The trial was stopped early for safety reasons. CONCLUSION In this study of children undergoing tonsillectomy, dexamethasone decreased the risk of PONV dose dependently but was associated with an increased risk of postoperative bleeding. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00403806.

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.

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 &mgr;g 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.

Ventilation strategies in obese patients undergoing surgery: a quantitative systematic review and meta-analysis

BACKGROUND Pathophysiological changes due to obesity may complicate mechanical ventilation during general anaesthesia. The ideal ventilation strategy is expected to optimize gas exchange and pulmonary mechanics and to reduce the risk of respiratory complications. METHODS Systematic search (databases, bibliographies, to March 2012, all languages) was performed for randomized trials testing intraoperative ventilation strategies in obese patients (BMI ≥ 30 kg m(-2)), and reporting on gas exchange, pulmonary mechanics, or pulmonary complications. Meta-analyses were performed when data from at least three studies or 100 patients could be combined. RESULTS Thirteen studies (505 obese surgical patients) reported on a variety of ventilation strategies: pressure- or volume-controlled ventilation (PCV, VCV), various tidal volumes, and different PEEP or recruitment manoeuvres (RM), and combinations thereof. Definitions and reporting of endpoints were inconsistent. In five trials (182 patients), RM added to PEEP compared with PEEP alone improved intraoperative PaO2/FIO2 ratio [weighted mean difference (WMD), 16.2 kPa; 95% confidence interval (CI), 8.0-24.4] and increased respiratory system compliance (WMD, 14 ml cm H(2)O(-1); 95% CI, 8-20). Arterial pressure remained unchanged. In four trials (100 patients) comparing PCV with VCV, there was no difference in PaO2/FIO2 ratio, tidal volume, or arterial pressure. Comparison of further ventilation strategies or combination of other outcomes was not feasible. Data on postoperative complications were seldom reported. CONCLUSIONS The ideal intraoperative ventilation strategy in obese patients remains obscure. There is some evidence that RM added to PEEP compared with PEEP alone improves intraoperative oxygenation and compliance without adverse effects. There is no evidence of any difference between PCV and VCV.

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.