Background
The unanticipated difficult airway is a potentially life‐threatening event during anaesthesia or acute conditions. An unsuccessfully managed upper airway is associated with serious ...morbidity and mortality. Several bedside screening tests are used in clinical practice to identify those at high risk of difficult airway. Their accuracy and benefit however, remains unclear.
Objectives
The objective of this review was to characterize and compare the diagnostic accuracy of the Mallampati classification and other commonly used airway examination tests for assessing the physical status of the airway in adult patients with no apparent anatomical airway abnormalities. We performed this individually for each of the four descriptors of the difficult airway: difficult face mask ventilation, difficult laryngoscopy, difficult tracheal intubation, and failed intubation.
Search methods
We searched major electronic databases including CENTRAL, MEDLINE, Embase, ISI Web of Science, CINAHL, as well as regional, subject specific, and dissertation and theses databases from inception to 16 December 2016, without language restrictions. In addition, we searched the Science Citation Index and checked the references of all the relevant studies. We also handsearched selected journals, conference proceedings, and relevant guidelines. We updated this search in March 2018, but we have not yet incorporated these results.
Selection criteria
We considered full‐text diagnostic test accuracy studies of any individual index test, or a combination of tests, against a reference standard. Participants were adults without obvious airway abnormalities, who were having laryngoscopy performed with a standard laryngoscope and the trachea intubated with a standard tracheal tube. Index tests included the Mallampati test, modified Mallampati test, Wilson risk score, thyromental distance, sternomental distance, mouth opening test, upper lip bite test, or any combination of these. The target condition was difficult airway, with one of the following reference standards: difficult face mask ventilation, difficult laryngoscopy, difficult tracheal intubation, and failed intubation.
Data collection and analysis
We performed screening and selection of the studies, data extraction and assessment of methodological quality (using QUADAS‐2) independently and in duplicate. We designed a Microsoft Access database for data collection and used Review Manager 5 and R for data analysis. For each index test and each reference standard, we assessed sensitivity and specificity. We produced forest plots and summary receiver operating characteristic (ROC) plots to summarize the data. Where possible, we performed meta‐analyses to calculate pooled estimates and compare test accuracy indirectly using bivariate models. We investigated heterogeneity and performed sensitivity analyses.
Main results
We included 133 (127 cohort type and 6 case‐control) studies involving 844,206 participants. We evaluated a total of seven different prespecified index tests in the 133 studies, as well as 69 non‐prespecified, and 32 combinations. For the prespecified index tests, we found six studies for the Mallampati test, 105 for the modified Mallampati test, six for the Wilson risk score, 52 for thyromental distance, 18 for sternomental distance, 34 for the mouth opening test, and 30 for the upper lip bite test. Difficult face mask ventilation was the reference standard in seven studies, difficult laryngoscopy in 92 studies, difficult tracheal intubation in 50 studies, and failed intubation in two studies. Across all studies, we judged the risk of bias to be variable for the different domains; we mostly observed low risk of bias for patient selection, flow and timing, and unclear risk of bias for reference standard and index test. Applicability concerns were generally low for all domains. For difficult laryngoscopy, the summary sensitivity ranged from 0.22 (95% confidence interval (CI) 0.13 to 0.33; mouth opening test) to 0.67 (95% CI 0.45 to 0.83; upper lip bite test) and the summary specificity ranged from 0.80 (95% CI 0.74 to 0.85; modified Mallampati test) to 0.95 (95% CI 0.88 to 0.98; Wilson risk score). The upper lip bite test for diagnosing difficult laryngoscopy provided the highest sensitivity compared to the other tests (P < 0.001). For difficult tracheal intubation, summary sensitivity ranged from 0.24 (95% CI 0.12 to 0.43; thyromental distance) to 0.51 (95% CI 0.40 to 0.61; modified Mallampati test) and the summary specificity ranged from 0.87 (95% CI 0.82 to 0.91; modified Mallampati test) to 0.93 (0.87 to 0.96; mouth opening test). The modified Mallampati test had the highest sensitivity for diagnosing difficult tracheal intubation compared to the other tests (P < 0.001). For difficult face mask ventilation, we could only estimate summary sensitivity (0.17, 95% CI 0.06 to 0.39) and specificity (0.90, 95% CI 0.81 to 0.95) for the modified Mallampati test.
Authors' conclusions
Bedside airway examination tests, for assessing the physical status of the airway in adults with no apparent anatomical airway abnormalities, are designed as screening tests. Screening tests are expected to have high sensitivities. We found that all investigated index tests had relatively low sensitivities with high variability. In contrast, specificities were consistently and markedly higher than sensitivities across all tests. The standard bedside airway examination tests should be interpreted with caution, as they do not appear to be good screening tests. Among the tests we examined, the upper lip bite test showed the most favourable diagnostic test accuracy properties. Given the paucity of available data, future research is needed to develop tests with high sensitivities to make them useful, and to consider their use for screening difficult face mask ventilation and failed intubation. The 27 studies in 'Studies awaiting classification' may alter the conclusions of the review, once we have assessed them.
Background
Initial goal‐directed resuscitation for hypotensive shock usually includes administration of intravenous fluids, followed by initiation of vasopressors. Despite obvious immediate effects ...of vasopressors on haemodynamics, their effect on patient‐relevant outcomes remains controversial. This review was published originally in 2004 and was updated in 2011 and again in 2016.
Objectives
Our objective was to compare the effect of one vasopressor regimen (vasopressor alone, or in combination) versus another vasopressor regimen on mortality in critically ill participants with shock. We further aimed to investigate effects on other patient‐relevant outcomes and to assess the influence of bias on the robustness of our effect estimates.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 Issue 6), MEDLINE, EMBASE, PASCAL BioMed, CINAHL, BIOSIS and PsycINFO (from inception to June 2015). We performed the original search in November 2003. We also asked experts in the field and searched meta‐registries to identify ongoing trials.
Selection criteria
Randomized controlled trials (RCTs) comparing various vasopressor regimens for hypotensive shock.
Data collection and analysis
Two review authors ed data independently. They discussed disagreements between them and resolved differences by consulting with a third review author. We used a random‐effects model to combine quantitative data.
Main results
We identified 28 RCTs (3497 participants) with 1773 mortality outcomes. Six different vasopressors, given alone or in combination, were studied in 12 different comparisons.
All 28 studies reported mortality outcomes; 12 studies reported length of stay. Investigators reported other morbidity outcomes in a variable and heterogeneous way. No data were available on quality of life nor on anxiety and depression outcomes. We classified 11 studies as having low risk of bias for the primary outcome of mortality; only four studies fulfilled all trial quality criteria.
In summary, researchers reported no differences in total mortality in any comparisons of different vasopressors or combinations in any of the pre‐defined analyses (evidence quality ranging from high to very low). More arrhythmias were observed in participants treated with dopamine than in those treated with norepinephrine (high‐quality evidence). These findings were consistent among the few large studies and among studies with different levels of within‐study bias risk.
Authors' conclusions
We found no evidence of substantial differences in total mortality between several vasopressors. Dopamine increases the risk of arrhythmia compared with norepinephrine and might increase mortality. Otherwise, evidence of any other differences between any of the six vasopressors examined is insufficient. We identified low risk of bias and high‐quality evidence for the comparison of norepinephrine versus dopamine and moderate to very low‐quality evidence for all other comparisons, mainly because single comparisons occasionally were based on only a few participants. Increasing evidence indicates that the treatment goals most often employed are of limited clinical value. Our findings suggest that major changes in clinical practice are not needed, but that selection of vasopressors could be better individualised and could be based on clinical variables reflecting hypoperfusion.
Background
The management of postoperative pain and recovery is still unsatisfactory in a number of cases in clinical practice. Opioids used for postoperative analgesia are frequently associated with ...adverse effects, including nausea and constipation, preventing smooth postoperative recovery. Not all patients are suitable for, and benefit from, epidural analgesia that is used to improve postoperative recovery. The non‐opioid, lidocaine, was investigated in several studies for its use in multimodal management strategies to reduce postoperative pain and enhance recovery. This review was published in 2015 and updated in January 2017.
Objectives
To assess the effects (benefits and risks) of perioperative intravenous (IV) lidocaine infusion compared to placebo/no treatment or compared to epidural analgesia on postoperative pain and recovery in adults undergoing various surgical procedures.
Search methods
We searched CENTRAL, MEDLINE, Embase, CINAHL, and reference lists of articles in January 2017. We searched one trial registry contacted researchers in the field, and handsearched journals and congress proceedings. We updated this search in February 2018, but have not yet incorporated these results into the review.
Selection criteria
We included randomized controlled trials comparing the effect of continuous perioperative IV lidocaine infusion either with placebo, or no treatment, or with thoracic epidural analgesia (TEA) in adults undergoing elective or urgent surgery under general anaesthesia. The IV lidocaine infusion must have been started intraoperatively, prior to incision, and continued at least until the end of surgery.
Data collection and analysis
We used Cochrane's standard methodological procedures. Our primary outcomes were: pain score at rest; gastrointestinal recovery and adverse events. Secondary outcomes included: postoperative nausea and postoperative opioid consumption. We used GRADE to assess the quality of evidence for each outcome.
Main results
We included 23 new trials in the update. In total, the review included 68 trials (4525 randomized participants). Two trials compared IV lidocaine with TEA. In all remaining trials, placebo or no treatment was used as a comparator. Trials involved participants undergoing open abdominal (22), laparoscopic abdominal (20), or various other surgical procedures (26). The application scheme of systemic lidocaine strongly varies between the studies related to both dose (1 mg/kg/h to 5 mg/kg/h) and termination of the infusion (from the end of surgery until several days after).
The risk of bias was low with respect to selection bias (random sequence generation), performance bias, attrition bias, and detection bias in more than 50% of the included studies. For allocation concealment and selective reporting, the quality assessment yielded low risk of bias for only approximately 20% of the included studies.
IV Lidocaine compared to placebo or no treatment
We are uncertain whether IV lidocaine improves postoperative pain compared to placebo or no treatment at early time points (1 to 4 hours) (standardized mean difference (SMD) −0.50, 95% confidence interval (CI) −0.72 to −0.28; 29 studies, 1656 participants; very low‐quality evidence) after surgery. Due to variation in the standard deviation (SD) in the studies, this would equate to an average pain reduction of between 0.37 cm and 2.48 cm on a 0 to 10 cm visual analogue scale . Assuming approximately 1 cm on a 0 to 10 cm pain scale is clinically meaningful, we ruled out a clinically relevant reduction in pain with lidocaine at intermediate (24 hours) (SMD −0.14, 95% CI −0.25 to −0.04; 33 studies, 1847 participants; moderate‐quality evidence), and at late time points (48 hours) (SMD −0.11, 95% CI −0.25 to 0.04; 24 studies, 1404 participants; moderate‐quality evidence). Due to variation in the SD in the studies, this would equate to an average pain reduction of between 0.10 cm to 0.48 cm at 24 hours and 0.08 cm to 0.42 cm at 48 hours. In contrast to the original review in 2015, we did not find any significant subgroup differences for different surgical procedures.
We are uncertain whether lidocaine reduces the risk of ileus (risk ratio (RR) 0.37, 95% CI 0.15 to 0.87; 4 studies, 273 participants), time to first defaecation/bowel movement (mean difference (MD) −7.92 hours, 95% CI −12.71 to −3.13; 12 studies, 684 participants), risk of postoperative nausea (overall, i.e. 0 up to 72 hours) (RR 0.78, 95% CI 0.67 to 0.91; 35 studies, 1903 participants), and opioid consumption (overall) (MD −4.52 mg morphine equivalents , 95% CI −6.25 to −2.79; 40 studies, 2201 participants); quality of evidence was very low for all these outcomes.
The effect of IV lidocaine on adverse effects compared to placebo treatment is uncertain, as only a small number of studies systematically analysed the occurrence of adverse effects (very low‐quality evidence).
IV Lidocaine compared to TEA
The effects of IV lidocaine compared with TEA are unclear (pain at 24 hours (MD 1.51, 95% CI −0.29 to 3.32; 2 studies, 102 participants), pain at 48 hours (MD 0.98, 95% CI −1.19 to 3.16; 2 studies, 102 participants), time to first bowel movement (MD −1.66, 95% CI −10.88 to 7.56; 2 studies, 102 participants); all very low‐quality evidence). The risk for ileus and for postoperative nausea (overall) is also unclear, as only one small trial assessed these outcomes (very low‐quality evidence). No trial assessed the outcomes, 'pain at early time points' and 'opioid consumption (overall)'. The effect of IV lidocaine on adverse effects compared to TEA is uncertain (very low‐quality evidence).
Authors' conclusions
We are uncertain whether IV perioperative lidocaine, when compared to placebo or no treatment, has a beneficial impact on pain scores in the early postoperative phase, and on gastrointestinal recovery, postoperative nausea, and opioid consumption. The quality of evidence was limited due to inconsistency, imprecision, and study quality. Lidocaine probably has no clinically relevant effect on pain scores later than 24 hours. Few studies have systematically assessed the incidence of adverse effects. There is a lack of evidence about the effects of IV lidocaine compared with epidural anaesthesia in terms of the optimal dose and timing (including the duration) of the administration. We identified three ongoing studies, and 18 studies are awaiting classification; the results of the review may change when these studies are published and included in the review.
Background
Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient ...dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiemetic drugs are available for prophylaxis. They have various mechanisms of action and side effects, but there is still uncertainty about which drugs are most effective with the fewest side effects.
Objectives
• To compare the efficacy and safety of different prophylactic pharmacologic interventions (antiemetic drugs) against no treatment, against placebo, or against each other (as monotherapy or combination prophylaxis) for prevention of postoperative nausea and vomiting in adults undergoing any type of surgery under general anaesthesia
• To generate a clinically useful ranking of antiemetic drugs (monotherapy and combination prophylaxis) based on efficacy and safety
• To identify the best dose or dose range of antiemetic drugs in terms of efficacy and safety
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and reference lists of relevant systematic reviews. The first search was performed in November 2017 and was updated in April 2020. In the update of the search, 39 eligible studies were found that were not included in the analysis (listed as awaiting classification).
Selection criteria
Randomized controlled trials (RCTs) comparing effectiveness or side effects of single antiemetic drugs in any dose or combination against each other or against an inactive control in adults undergoing any type of surgery under general anaesthesia. All antiemetic drugs belonged to one of the following substance classes: 5‐HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, corticosteroids, antihistamines, and anticholinergics. No language restrictions were applied. publications were excluded.
Data collection and analysis
A review team of 11 authors independently assessed trials for inclusion and risk of bias and subsequently extracted data. We performed pair‐wise meta‐analyses for drugs of direct interest (amisulpride, aprepitant, casopitant, dexamethasone, dimenhydrinate, dolasetron, droperidol, fosaprepitant, granisetron, haloperidol, meclizine, methylprednisolone, metoclopramide, ondansetron, palonosetron, perphenazine, promethazine, ramosetron, rolapitant, scopolamine, and tropisetron) compared to placebo (inactive control). We performed network meta‐analyses (NMAs) to estimate the relative effects and ranking (with placebo as reference) of all available single drugs and combinations. Primary outcomes were vomiting within 24 hours postoperatively, serious adverse events (SAEs), and any adverse event (AE). Secondary outcomes were drug class‐specific side effects (e.g. headache), mortality, early and late vomiting, nausea, and complete response. We performed subgroup network meta‐analysis with dose of drugs as a moderator variable using dose ranges based on previous consensus recommendations. We assessed certainty of evidence of NMA treatment effects for all primary outcomes and drug class‐specific side effects according to GRADE (CINeMA, Confidence in Network Meta‐Analysis). We restricted GRADE assessment to single drugs of direct interest compared to placebo.
Main results
We included 585 studies (97,516 randomized participants). Most of these studies were small (median sample size of 100); they were published between 1965 and 2017 and were primarily conducted in Asia (51%), Europe (25%), and North America (16%). Mean age of the overall population was 42 years. Most participants were women (83%), had American Society of Anesthesiologists (ASA) physical status I and II (70%), received perioperative opioids (88%), and underwent gynaecologic (32%) or gastrointestinal surgery (19%) under general anaesthesia using volatile anaesthetics (88%).
In this review, 44 single drugs and 51 drug combinations were compared. Most studies investigated only single drugs (72%) and included an inactive control arm (66%). The three most investigated single drugs in this review were ondansetron (246 studies), dexamethasone (120 studies), and droperidol (97 studies).
Almost all studies (89%) reported at least one efficacy outcome relevant for this review. However, only 56% reported at least one relevant safety outcome.
Altogether, 157 studies (27%) were assessed as having overall low risk of bias, 101 studies (17%) overall high risk of bias, and 327 studies (56%) overall unclear risk of bias.
Vomiting within 24 hours postoperatively
Relative effects from NMA for vomiting within 24 hours (282 RCTs, 50,812 participants, 28 single drugs, and 36 drug combinations) suggest that 29 out of 36 drug combinations and 10 out of 28 single drugs showed a clinically important benefit (defined as the upper end of the 95% confidence interval (CI) below a risk ratio (RR) of 0.8) compared to placebo. Combinations of drugs were generally more effective than single drugs in preventing vomiting. However, single NK₁ receptor antagonists showed treatment effects similar to most of the drug combinations. High‐certainty evidence suggests that the following single drugs reduce vomiting (ordered by decreasing efficacy): aprepitant (RR 0.26, 95% CI 0.18 to 0.38, high certainty, rank 3/28 of single drugs); ramosetron (RR 0.44, 95% CI 0.32 to 0.59, high certainty, rank 5/28); granisetron (RR 0.45, 95% CI 0.38 to 0.54, high certainty, rank 6/28); dexamethasone (RR 0.51, 95% CI 0.44 to 0.57, high certainty, rank 8/28); and ondansetron (RR 0.55, 95% CI 0.51 to 0.60, high certainty, rank 13/28). Moderate‐certainty evidence suggests that the following single drugs probably reduce vomiting: fosaprepitant (RR 0.06, 95% CI 0.02 to 0.21, moderate certainty, rank 1/28) and droperidol (RR 0.61, 95% CI 0.54 to 0.69, moderate certainty, rank 20/28).
Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol showed clinically important benefit, but low doses showed no clinically important benefit. Aprepitant was used mainly at high doses, ramosetron at recommended doses, and fosaprepitant at doses of 150 mg (with no dose recommendation available).
Frequency of SAEs
Twenty‐eight RCTs were included in the NMA for SAEs (10,766 participants, 13 single drugs, and eight drug combinations). The certainty of evidence for SAEs when using one of the best and most reliable anti‐vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to low. Droperidol (RR 0.88, 95% CI 0.08 to 9.71, low certainty, rank 6/13) may reduce SAEs. We are uncertain about the effects of aprepitant (RR 1.39, 95% CI 0.26 to 7.36, very low certainty, rank 11/13), ramosetron (RR 0.89, 95% CI 0.05 to 15.74, very low certainty, rank 7/13), granisetron (RR 1.21, 95% CI 0.11 to 13.15, very low certainty, rank 10/13), dexamethasone (RR 1.16, 95% CI 0.28 to 4.85, very low certainty, rank 9/13), and ondansetron (RR 1.62, 95% CI 0.32 to 8.10, very low certainty, rank 12/13). No studies reporting SAEs were available for fosaprepitant.
Frequency of any AE
Sixty‐one RCTs were included in the NMA for any AE (19,423 participants, 15 single drugs, and 11 drug combinations). The certainty of evidence for any AE when using one of the best and most reliable anti‐vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to moderate. Granisetron (RR 0.92, 95% CI 0.80 to 1.05, moderate certainty, rank 7/15) probably has no or little effect on any AE. Dexamethasone (RR 0.77, 95% CI 0.55 to 1.08, low certainty, rank 2/15) and droperidol (RR 0.89, 95% CI 0.81 to 0.98, low certainty, rank 6/15) may reduce any AE. Ondansetron (RR 0.95, 95% CI 0.88 to 1.01, low certainty, rank 9/15) may have little or no effect on any AE. We are uncertain about the effects of aprepitant (RR 0.87, 95% CI 0.78 to 0.97, very low certainty, rank 3/15) and ramosetron (RR 1.00, 95% CI 0.65 to 1.54, very low certainty, rank 11/15) on any AE. No studies reporting any AE were available for fosaprepitant.
Class‐specific side effects
For class‐specific side effects (headache, constipation, wound infection, extrapyramidal symptoms, sedation, arrhythmia, and QT prolongation) of relevant substances, the certainty of evidence for the best and most reliable anti‐vomiting drugs mostly ranged from very low to low. Exceptions were that ondansetron probably increases headache (RR 1.16, 95% CI 1.06 to 1.28, moderate certainty, rank 18/23) and probably reduces sedation (RR 0.87, 95% CI 0.79 to 0.96, moderate certainty, rank 5/24) compared to placebo. The latter effect is limited to recommended and high doses of ondansetron. Droperidol probably reduces headache (RR 0.76, 95% CI 0.67 to 0.86, moderate certainty, rank 5/23) compared to placebo. We have high‐certainty evidence that dexamethasone (RR 1.00, 95% CI 0.91 to 1.09, high certainty, rank 16/24) has no effect on sedation compared to placebo. No studies assessed substance class‐specific side effects for fosaprepitant.
Direction and magnitude of network effect estimates together with level of evidence certainty are graphically summarized for all pre‐defined GRADE‐relevant outcomes and all drugs of direct interest compared to placebo in http://doi.org/10.5281/zenodo.4066353.
Authors' conclusions
We found high‐certainty evidence that five single drugs (aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron) reduce vomiting, and moderate‐certainty evidence that two other single drugs (fosaprepitant and droperidol) probably reduce vomiting, compared to placebo. Four of the six
Sequential design methods for binary response variables exist for determination of the concentration or dose associated with the 50% point along the dose-response curve; the up-and-down method of ...Dixon and Mood is now commonly used in anesthesia research. There have been important developments in statistical methods that (1) allow the design of experiments for the measurement of the response at any point (quantile) along the dose-response curve, (2) demonstrate the risk of certain statistical methods commonly used in literature reports, (3) allow the estimation of the concentration or dose-the target dose-associated with the chosen quantile without the assumption of the symmetry of the tolerance distribution, and (4) set bounds on the probability of response at this target dose. This article details these developments, briefly surveys current use of the up-and-down method in anesthesia research, reanalyzes published reports using the up-and-down method for the study of the epidural relief of pain during labor, and discusses appropriate inferences from up-and-down method studies.
Background
Approximately 30% of adults undergoing non‐cardiac surgery suffer from preoperative anaemia. Preoperative anaemia is a risk factor for mortality and adverse outcomes in different surgical ...specialties and is frequently the reason for blood transfusion. The most common causes are renal, chronic diseases, and iron deficiency. International guidelines recommend that the cause of anaemia guide preoperative anaemia treatment. Recombinant human erythropoietin (rHuEPO) with iron supplementation has frequently been used to increase preoperative haemoglobin concentrations in patients in order to avoid the need for perioperative allogeneic red blood cell (RBC) transfusion.
Objectives
To evaluate the efficacy of preoperative rHuEPO therapy (subcutaneous or parenteral) with iron (enteral or parenteral) in reducing the need for allogeneic RBC transfusions in preoperatively anaemic adults undergoing non‐cardiac surgery.
Search methods
We searched CENTRAL, Ovid MEDLINE(R), Ovid Embase, ISI Web of Science: SCI‐EXPANDED and CPCI‐S, and clinical trial registries WHO ICTRP and ClinicalTrials.gov on 29 August 2019.
Selection criteria
We included all randomized controlled trials (RCTs) that compared preoperative rHuEPO + iron therapy to control treatment (placebo, no treatment, or standard of care with or without iron) for preoperatively anaemic adults undergoing non‐cardiac surgery.
We used the World Health Organization (WHO) definition of anaemia: haemoglobin concentration (g/dL) less than 13 g/dL for males, and 12 g/dL for non‐pregnant females (decision of inclusion based on mean haemoglobin concentration). We defined two subgroups of rHuEPO dosage: 'low' for 150 to 300 international units (IU)/kg body weight, and 'high' for 500 to 600 IU/kg body weight.
Data collection and analysis
Two review authors collected data from the included studies. Our primary outcome was the need for RBC transfusion (no autologous transfusion, fresh frozen plasma or platelets), measured in transfused participants during surgery (intraoperative) and up to five days after surgery. Secondary outcomes of interest were: haemoglobin concentration (directly before surgery), number of RBC units (where one unit contains 250 to 450 mL) transfused per participant (intraoperative and up to five days after surgery), mortality (within 30 days after surgery), length of hospital stay, and adverse events (e.g. renal dysfunction, thromboembolism, hypertension, allergic reaction, headache, fever, constipation).
Main results
Most of the included trials were in orthopaedic, gastrointestinal, and gynaecological surgery and included participants with mild and moderate preoperative anaemia (haemoglobin from 10 to 12 g/dL). The duration of preoperative rHuEPO treatment varied across the trials, ranging from once a week to daily or a 5‐to‐10‐day period, and in one trial preoperative rHuEPO was given on the morning of surgery and for five days postoperatively.
We included 12 trials (participants = 1880) in the quantitative analysis of the need for RBC transfusion following preoperative treatment with rHuEPO + iron to correct preoperative anaemia in non‐cardiac surgery; two studies were multiarmed trials with two different dose regimens.
Preoperative rHuEPO + iron given to anaemic adults reduced the need RBC transfusion (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.38 to 0.80; participants = 1880; studies = 12; I2 = 84%; moderate‐quality evidence due to inconsistency). This analysis suggests that on average, the combined administration of rHuEPO + iron will mean 231 fewer individuals will need transfusion for every 1000 individuals compared to the control group.
Preoperative high‐dose rHuEPO + iron given to anaemic adults increased the haemoglobin concentration (mean difference (MD) 1.87 g/dL, 95% CI 1.26 to 2.49; participants = 852; studies = 3; I2 = 89%; low‐quality evidence due to inconsistency and risk of bias) but not low‐dose rHuEPO + iron (MD 0.11 g/dL, 95% CI −0.46 to 0.69; participants = 334; studies = 4; I2 = 69%; low‐quality evidence due to inconsistency and risk of bias).
There was probably little or no difference in the number of RBC units when rHuEPO + iron was given preoperatively (MD −0.09, 95% CI −0.23 to 0.05; participants = 1420; studies = 6; I2 = 2%; moderate‐quality evidence due to imprecision).
There was probably little or no difference in the risk of mortality within 30 days of surgery (RR 1.19, 95% CI 0.39 to 3.63; participants = 230; studies = 2; I2 = 0%; moderate‐quality evidence due to imprecision) or of adverse events including local rash, fever, constipation, or transient hypertension (RR 0.93, 95% CI 0.68 to 1.28; participants = 1722; studies = 10; I2 = 0%; moderate‐quality evidence due to imprecision).
The administration of rHuEPO + iron before non‐cardiac surgery did not clearly reduce the length of hospital stay of preoperative anaemic adults (MD −1.07, 95% CI −4.12 to 1.98; participants = 293; studies = 3; I2 = 87%; low‐quality evidence due to inconsistency and imprecision).
Authors' conclusions
Moderate‐quality evidence suggests that preoperative rHuEPO + iron therapy for anaemic adults prior to non‐cardiac surgery reduces the need for RBC transfusion and, when given at higher doses, increases the haemoglobin concentration preoperatively. The administration of rHuEPO + iron treatment did not decrease the mean number of units of RBC transfused per patient.
There were no important differences in the risk of adverse events or mortality within 30 days, nor in length of hospital stay. Further, well‐designed, adequately powered RCTs are required to estimate the impact of this combined treatment more precisely.
Background
Spinal anaesthesia has been implicated as one of the possible causes of neurological complications following surgical procedures. This painful condition, occurring during the immediate ...postoperative period, is termed transient neurological symptoms (TNS) and is typically observed after the use of spinal lidocaine. Alternatives to lidocaine that can provide high‐quality anaesthesia without TNS development are needed. This review was originally published in 2005, and last updated in 2009.
Objectives
To determine the frequency of TNS after spinal anaesthesia with lidocaine and compare it with other types of local anaesthetics by performing a meta‐analysis for all pair‐wise comparisons, and conducting network meta‐analysis (NMA) to rank interventions.
Search methods
We searched CENTRAL, MEDLINE, Elsevier Embase, and LILACS on 25 November 2018. We searched clinical trial registries and handsearched the reference lists of trials and review articles.
Selection criteria
We included randomized and quasi‐randomized controlled trials comparing the frequency of TNS after spinal anaesthesia with lidocaine to other local anaesthetics. Studies had to have two or more arms that used distinct local anaesthetics (irrespective of the concentration and baricity of the solution) for spinal anaesthesia in preparation for surgery.
We included adults who received spinal anaesthesia and considered all pregnant participants as a subgroup. The follow‐up period for TNS was at least 24 hours.
Data collection and analysis
Four review authors independently assessed studies for inclusion. Three review authors independently evaluated the quality of the relevant studies and extracted the data from the included studies. We performed meta‐analysis for all pair‐wise comparisons of local anaesthetics, as well as NMA.
We used an inverse variance weighting for summary statistics and a random‐effects model as we expected methodological and clinical heterogeneity across the included studies resulting in varying effect sizes between studies of pair‐wise comparisons. The NMA used all included studies based on a graph theoretical approach within a frequentist framework. Finally, we ranked the competing treatments by P scores.
Main results
The analysis included 24 trials reporting on 2226 participants of whom 239 developed TNS. Two studies are awaiting classification and one is ongoing. Included studies mostly had unclear to high risk of bias.
The NMA included 24 studies and eight different local anaesthetics; the number of pair‐wise comparisons was 32 and the number of different pair‐wise comparisons was 11. This analysis showed that, compared to lidocaine, the risk ratio (RR) of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine with RRs in the range of 0.10 to 0.23 while 2‐chloroprocaine and mepivacaine did not differ in terms of RR of TNS development compared to lidocaine.
Pair‐wise meta‐analysis showed that compared with lidocaine, most local anaesthetics were associated with a reduced risk of TNS development (except 2‐chloroprocaine and mepivacaine) (bupivacaine: RR 0.16, 95% confidence interval (CI) 0.09 to 0.28; 12 studies; moderate‐quality evidence; 2‐chloroprocaine: RR 0.09, 95% CI 0.01 to 1.51; 2 studies; low‐quality evidence; levobupivacaine: RR 0.13, 95% CI 0.02 to 0.69; 2 studies; low‐quality evidence; mepivacaine: RR 1.01, 95% CI 0.18 to 5.82; 4 studies; very low‐quality evidence; prilocaine: RR 0.18, 95% CI 0.07 to 0.49; 4 studies; moderate‐quality evidence; procaine: RR 0.14, 95% CI 0.04 to 0.52; 2 studies; moderate‐quality evidence; ropivacaine: RR 0.10, 95% CI 0.01 to 0.78; 2 studies; low‐quality evidence).
We were unable to perform any of our planned subgroup analyses due to the low number of TNS events.
Authors' conclusions
Results from both NMA and pair‐wise meta‐analysis indicate that the risk of developing TNS after spinal anaesthesia is lower when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine are used compared to lidocaine. The use of 2‐chloroprocaine and mepivacaine had a similar risk to lidocaine in terms of TNS development after spinal anaesthesia.
Patients should be informed of TNS as a possible adverse effect of local anaesthesia with lidocaine and the choice of anaesthetic agent should be based on the specific clinical context and parameters such as the expected duration of the procedure and the quality of anaesthesia.
Due to the very low‐ to moderate‐quality evidence (GRADE), future research efforts in this field are required to assess alternatives to lidocaine that would be able to provide high‐quality anaesthesia without TNS development. The two studies awaiting classification and one ongoing study may alter the conclusions of the review once assessed.
There is insufficient prospective evidence regarding the relationship between surgical experience and prolonged opioid use and pain. The authors investigated the association of patient ...characteristics, surgical procedure, and perioperative anesthetic course with postoperative opioid consumption and pain 3 months postsurgery. The authors hypothesized that patient characteristics and intraoperative factors predict opioid consumption and pain 3 months postsurgery.
Eleven U.S. and one European institution enrolled patients scheduled for spine, open thoracic, knee, hip, or abdominal surgery, or mastectomy, in this multicenter, prospective observational study. Preoperative and postoperative data were collected using patient surveys and electronic medical records. Intraoperative data were collected from the Multicenter Perioperative Outcomes Group database. The association between postoperative opioid consumption and surgical site pain at 3 months, elicited from a telephone survey conducted at 3 months postoperatively, and demographics, psychosocial scores, pain scores, pain management, and case characteristics, was analyzed.
Between September and October 2017, 3,505 surgical procedures met inclusion criteria. A total of 1,093 cases were included; 413 patients were lost to follow-up, leaving 680 (64%) for outcome analysis. Preoperatively, 135 (20%) patients were taking opioids. Three months postsurgery, 96 (14%) patients were taking opioids, including 23 patients (4%) who had not taken opioids preoperatively. A total of 177 patients (27%) reported surgical site pain, including 45 (13%) patients who had not reported pain preoperatively. The adjusted odds ratio for 3-month opioid use was 18.6 (credible interval, 10.3 to 34.5) for patients who had taken opioids preoperatively. The adjusted odds ratio for 3-month surgical site pain was 2.58 (1.45 to 4.4), 4.1 (1.73 to 8.9), and 2.75 (1.39 to 5.0) for patients who had site pain preoperatively, knee replacement, or spine surgery, respectively.
Preoperative opioid use was the strongest predictor of opioid use 3 months postsurgery. None of the other variables showed clinically significant association with opioid use at 3 months after surgery.
Objective To systematically determine the most efficacious approach for preventing pain on injection of propofol.Design Systematic review and meta-analysis.Data sources PubMed, Embase, Cochrane ...Library, www.clinicaltrials.gov, and hand searching from the reference lists of identified papers.Study selection Randomised controlled trials comparing drug and non-drug interventions with placebo or another intervention to alleviate pain on injection of propofol in adults.Results Data were analysed from 177 randomised controlled trials totalling 25 260 adults. The overall risk of pain from propofol injection alone was about 60%. Using an antecubital vein instead of a hand vein was the most effective single intervention (relative risk 0.14, 95% confidence interval 0.07 to 0.30). Pretreatment using lidocaine (lignocaine) in conjunction with venous occlusion was similarly effective (0.29, 0.22 to 0.38). Other effective interventions were a lidocaine-propofol admixture (0.40, 0.33 to 0.48); pretreatment with lidocaine (0.47, 0.40 to 0.56), opioids (0.49, 0.41 to 0.59), ketamine (0.52, 0.46 to 0.57), or non-steroidal anti-inflammatory drugs (0.67, 0.49 to 0.91); and propofol emulsions containing medium and long chain triglycerides (0.75, 0.67 to 0.84). Statistical testing of indirect comparisons showed that use of the antecubital vein and pretreatment using lidocaine along with venous occlusion to be more efficacious than the other interventions.Conclusions The two most efficacious interventions to reduce pain on injection of propofol were use of the antecubital vein, or pretreatment using lidocaine in conjunction with venous occlusion when the hand vein was chosen. Under the assumption of independent efficacy a third practical alternative could be pretreatment of the hand vein with lidocaine or ketamine and use of a propofol emulsion containing medium and long chain triglycerides. Although not the most effective intervention on its own, a small dose of opioids before induction halved the risk of pain from the injection and thus can generally be recommended unless contraindicated.
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