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.
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.
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.
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.
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.
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 TEAThe 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).
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.
Tumescent lidocaine anesthesia consists of subcutaneous injection of relatively large volumes (up to 4 L or more) of dilute lidocaine (≤1 g/L) and epinephrine (≤1 mg/L). Although tumescent lidocaine ...anesthesia is used for an increasing variety of surgical procedures, the maximum safe dosage is unknown. Our primary aim in this study was to measure serum lidocaine concentrations after subcutaneous administration of tumescent lidocaine with and without liposuction. Our hypotheses were that even with large doses (i.e., >30 mg/kg), serum lidocaine concentrations would be below levels associated with mild toxicity and that the concentration-time profile would be lower after liposuction than without liposuction.
Volunteers participated in 1 to 2 infiltration studies without liposuction and then one study with tumescent liposuction totally by local anesthesia. Serum lidocaine concentrations were measured at 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours after each tumescent lidocaine infiltration. Area under the curve (AUC∞) of the serum lidocaine concentration-time profiles and peak serum lidocaine concentrations (Cmax) were determined with and without liposuction. For any given milligram per kilogram dosage, the probability that Cmax >6 μg/mL, the threshold for mild lidocaine toxicity was estimated using tolerance interval analysis.
In 41 tumescent infiltration procedures among 14 volunteer subjects, tumescent lidocaine dosages ranged from 19.2 to 52 mg/kg. Measured serum lidocaine concentrations were all <6 μg/mL over the 24-hour study period. AUC∞s with liposuction were significantly less than those without liposuction (P = 0.001). The estimated risk of lidocaine toxicity without liposuction at a dose of 28 mg/kg and with liposuction at a dose of 45 mg/kg was ≤1 per 2000.
Preliminary estimates for maximum safe dosages of tumescent lidocaine are 28 mg/kg without liposuction and 45 mg/kg with liposuction. As a result of delayed systemic absorption, these dosages yield serum lidocaine concentrations below levels associated with mild toxicity and are a nonsignificant risk of harm to patients.
Summary
Intravenous lidocaine is used widely for its effect on postoperative pain and recovery but it can be, and has been, fatal when used inappropriately and incorrectly. The risk‐benefit ratio of ...i.v. lidocaine varies with type of surgery and with patient factors such as comorbidity (including pre‐existing chronic pain). This consensus statement aims to address three questions. First, does i.v. lidocaine effectively reduce postoperative pain and facilitate recovery? Second, is i.v. lidocaine safe? Third, does the fact that i.v. lidocaine is not licensed for this indication affect its use? We suggest that i.v. lidocaine should be regarded as a ‘high‐risk’ medicine. Individual anaesthetists may feel that, in selected patients, i.v. lidocaine may be beneficial as part of a multimodal peri‐operative pain management strategy. This approach should be approved by hospital medication governance systems, and the individual clinical decision should be made with properly informed consent from the patient concerned. If i.v. lidocaine is used, we recommend an initial dose of no more than 1.5 mg.kg‐1, calculated using the patient’s ideal body weight and given as an infusion over 10 min. Thereafter, an infusion of no more than 1.5 mg.kg‐1.h‐1 for no longer than 24 h is recommended, subject to review and re‐assessment. Intravenous lidocaine should not be used at the same time as, or within the period of action of, other local anaesthetic interventions. This includes not starting i.v. lidocaine within 4 h after any nerve block, and not performing any nerve block until 4 h after discontinuing an i.v. lidocaine infusion.
Local anesthetics are used clinically for the control of postoperative pain management. This study aimed to develop chitosan (CS) with genipin (GP) hydrogels as the hydrophilic lipid shell loaded ...poly(ε-caprolactone) (PC) nanocapsules as the hydrophobic polymeric core composites (CS-GP/PC) to deliver bupivacaine (BPV) for the prolongation of anesthesia and pain relief. The swelling ratio, in vitro degradation, and rheological properties enhancement of CS-GP/PC polymeric hydrogel. The incorporation of PC nanocapsules into CS-GP hydrogels was confirmed by SEM, FTIR, and XRD analysis. Scanning electron microscopy results demonstrated that the CS-GP hydrogels and CS-GP/PC polymeric hydrogels have a porous structure, the pore dimensions being non-uniform with diameters between 25 and 300 μm. The in vitro drug release profile of CS-GP/PC polymeric hydrogel has been achieved 99.2 ± 1.12% of BPV drug release in 36 h. Cellular viability was evaluated using the CCK-8 test on 3T3 fibroblast cells revealed that the obtained CS-GP/PC polymeric hydrogel with BPV exhibited no obvious cytotoxicity. The CS-GP/PC polymeric hydrogel loaded with BPV showed significant improvement in pain response compared to the control group animals for at least 7 days. When compared with BPV solution, CS-GP hydrogel and CS-GP/PC polymeric hydrogel improved the skin permeation of BPV 3-fold and 5-fold in 24 h, respectively. In vitro and in vivo results pointed out PC nanocapsules loaded CS-GP hydrogel can act as effective drug carriers, thus prolonging and enhancing the anesthetic effect of BPV. Histopathological results demonstrated the excellent biodegradability and biocompatibility of the BPV-loaded CS-GP/PC polymeric hydrogel system on 7, 14, and 21 days without neurotoxicity.
HIGHLIGHTS
Preparation and characterization of CS-GP/PC polymeric hydrogel system.
BPV-loaded CS-GP/PC exhibited prolonged in vitro release in PBS solution.
Cytotoxicity of BPV-loaded CS-GP/PC polymeric hydrogel against fibroblast (3T3) cells.
Development of CS-GP/PC a promising skin drug-delivery system for local anesthetic BPV.
Safe and efficacious modalities of perioperative analgesia are essential for enhanced recovery after surgery. Truncal nerve blocks are one potential adjunct for analgesia of the abdominal wall, and ...in recent years their popularity has increased. Transversus abdominis plane block (TAPB) and rectus sheath block (RSB) have been shown to reduce morphine consumption and improve pain relief after abdominal surgery. These blocks typically require large volumes of local anaesthetic (LA). We aimed to synthesize studies evaluating systemic concentrations of LA after perioperative TAP and RSB to enhance our understanding of systemic LA absorption and the risk of systemic toxicity.
An independent literature review was performed in accordance with the methods outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. An electronic search of four databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and PubMed) was conducted. Primary articles measuring systemic concentrations of LA after single-shot bolus TAPB or RSB were included.
Fifteen studies met the inclusion criteria. Rapid systemic LA absorption was observed in all studies. Of a total of 381 patients, mean peak concentrations of LA exceeded toxic thresholds in 33 patients, of whom three reported mild adverse effects. The addition of epinephrine reduced systemic absorption of LA. No instances of seizure or cardiac instability were observed.
Local anaesthetic in TAPB and RSB can lead to detectable systemic concentrations that exceed commonly accepted thresholds of LA systemic toxicity. Our study highlights that these techniques are relatively safe with regard to LA systemic toxicity.
Peripheral nerve blocks for hip fractures Guay, Joanne; Parker, Martyn J; Griffiths, Richard ...
Cochrane database of systematic reviews,
05/2017, Volume:
5
Journal Article
Peer reviewed
Open access
Various nerve blocks with local anaesthetic agents have been used to reduce pain after hip fracture and subsequent surgery. This review was published originally in 1999 and was updated in 2001, 2002, ...2009 and 2017.
This review focuses on the use of peripheral nerves blocks as preoperative analgesia, as postoperative analgesia or as a supplement to general anaesthesia for hip fracture surgery. We undertook the update to look for new studies and to update the methods to reflect Cochrane standards.
For the updated review, we searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE (Ovid SP, 1966 to August week 1 2016), Embase (Ovid SP, 1988 to 2016 August week 1) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO, 1982 to August week 1 2016), as well as trial registers and reference lists of relevant articles.
We included randomized controlled trials (RCTs) involving use of nerve blocks as part of the care provided for adults aged 16 years and older with hip fracture.
Two review authors independently assessed new trials for inclusion, determined trial quality using the Cochrane tool and extracted data. When appropriate, we pooled results of outcome measures. We rated the quality of evidence according to the GRADE Working Group approach.
We included 31 trials (1760 participants; 897 randomized to peripheral nerve blocks and 863 to no regional blockade). Results of eight trials with 373 participants show that peripheral nerve blocks reduced pain on movement within 30 minutes of block placement (standardized mean difference (SMD) -1.41, 95% confidence interval (CI) -2.14 to -0.67; equivalent to -3.4 on a scale from 0 to 10; I
= 90%; high quality of evidence). Effect size was proportionate to the concentration of local anaesthetic used (P < 0.00001). Based on seven trials with 676 participants, we did not find a difference in the risk of acute confusional state (risk ratio (RR) 0.69, 95% CI 0.38 to 1.27; I
= 48%; very low quality of evidence). Three trials with 131 participants reported decreased risk for pneumonia (RR 0.41, 95% CI 0.19 to 0.89; I
= 3%; number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 5 to 72; moderate quality of evidence). We did not find a difference in risk of myocardial ischaemia or death within six months, but the number of participants included was well below the optimal information size for these two outcomes. Two trials with 155 participants reported that peripheral nerve blocks also reduced time to first mobilization after surgery (mean difference -11.25 hours, 95% CI -14.34 to -8.15 hours; I
= 52%; moderate quality of evidence). One trial with 75 participants indicated that the cost of analgesic drugs was lower when they were given as a single shot block (SMD -3.48, 95% CI -4.23 to -2.74; moderate quality of evidence).
High-quality evidence shows that regional blockade reduces pain on movement within 30 minutes after block placement. Moderate-quality evidence shows reduced risk for pneumonia, decreased time to first mobilization and cost reduction of the analgesic regimen (single shot blocks).
Perioperative Use of Intravenous Lidocaine Beaussier, Marc; Delbos, Alain; Maurice-Szamburski, Axel ...
Drugs (New York, N.Y.),
08/2018, Volume:
78, Issue:
12
Journal Article
Peer reviewed
Lidocaine is an amide local anaesthetic initially used intravenously as an antiarrhythmic agent. At some point it was proposed that intravenous lidocaine (IVL) had an analgesic effect that could be ...potentially beneficial in perioperative settings. Since these preliminary reports, a large body of evidence confirmed that IVL had anti-inflammatory and opiate-sparing effects, a combination of characteristics leading to an array of effects such as a decrease in postoperative pain and opiate consumption, and a reduction in the duration of digestive ileus. Additional studies demonstrated IVL to possess antithrombotic, antimicrobial and antitumoral effects. Beneficial effects of IVL have been characterized in abdominal surgery but remain controversial in other types of surgeries. Because the quality of evidence was limited, due to inconsistency, imprecision and study quality, recent conclusions from meta-analysis pooling together all types of surgery stated the uncertainty about IVL benefits. Additional indications such as the prevention of propofol-induced injection pain, prevention of hyperalgesia, protection against bronchial reactivity by bronchotracheal relaxation during surgery, and the increase in depth of general anaesthesia have since emerged. IVL is rapidly distributed in the body and metabolized by the liver. With the commonly recommended doses, lidocaine's therapeutic index remains very high and the plasma concentrations stay largely below the cardiotoxic and neurotoxic threshold levels, a notion that may be used by clinicians to draw conclusions on the benefit-risk profile of IVL in comparison to other analgesic strategies. The purpose of this review is to address the pharmacokinetic and pharmacodynamic properties of lidocaine in healthy and pathological conditions.
This review was published originally in 1999 and was updated in 2001, 2002, 2009, 2017, and 2020. Updating was deemed necessary due to the high incidence of hip fractures, the large number of ...official societies providing recommendations on this condition, the possibility that perioperative peripheral nerve blocks (PNBs) may improve patient outcomes, and the major role that PNBs may play in reducing preoperative and postoperative opioid use for analgesia.
To compare PNBs used as preoperative analgesia, as postoperative analgesia, or as a supplement to general anaesthesia versus no nerve block (or sham block) for adults with hip fracture. Outcomes were pain on movement at 30 minutes after block placement, acute confusional state, myocardial infarction, chest infection, death, time to first mobilization, and costs of an analgesic regimen for single-injection blocks. We undertook the update to look for new studies and to update the methods to reflect Cochrane standards.
For the updated review, we searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 11), in the Cochrane Library; MEDLINE (Ovid SP, 1966 to November 2019); Embase (Ovid SP, 1974 to November 2019); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO, 1982 to November 2019), as well as trial registers and reference lists of relevant articles.
We included randomized controlled trials (RCTs) assessing use of PNBs compared with no nerve block (or sham block) as part of the care provided for adults 16 years of age and older with hip fracture. DATA COLLECTION AND ANALYSIS: Two review authors independently screened new trials for inclusion, assessed trial quality using the Cochrane Risk of Bias-2 tool, and extracted data. When appropriate, we pooled results of outcome measures. We rated the certainty of evidence using the GRADE approach.
We included 49 trials (3061 participants; 1553 randomized to PNBs and 1508 to no nerve block (or sham block)). For this update, we added 18 new trials. Trials were published from 1981 to 2020. Trialists followed participants for periods ranging from 5 minutes to 12 months. The average age of participants ranged from 59 to 89 years. People with dementia were often excluded from the included trials. Additional analgesia was available for all participants. Results of 11 trials with 503 participants show that PNBs reduced pain on movement within 30 minutes of block placement (standardized mean difference (SMD) -1.05, 95% confidence interval (CI) -1.25 to -0.86; equivalent to -2.5 on a scale from 0 to 10; high-certainty evidence). Effect size was proportionate to the concentration of local anaesthetic used (P = 0.0003). Based on 13 trials with 1072 participants, PNBs reduce the risk of acute confusional state (risk ratio (RR) 0.67, 95% CI 0.50 to 0.90; number needed to treat for an additional beneficial outcome (NNTB) 12, 95% CI 7 to 47; high-certainty evidence). For myocardial infarction, there were no events in one trial with 31 participants (RR not estimable; low-certainty evidence). From three trials with 131 participants, PNBs probably reduce the risk for chest infection (RR 0.41, 95% CI 0.19 to 0.89; NNTB 7, 95% CI 5 to 72; moderate-certainty evidence). Based on 11 trials with 617 participants, the effects of PNBs on mortality within six months are uncertain due to very serious imprecision (RR 0.87, 95% CI 0.47 to 1.60; low-certainty evidence). From three trials with 208 participants, PNBs likely reduce time to first mobilization (mean difference (MD) -10.80 hours, 95% CI -12.83 to -8.77 hours; moderate-certainty evidence). One trial with 75 participants indicated there may be a small reduction in the cost of analgesic drugs with a single-injection PNB (MD -4.40 euros, 95% CI -4.84 to -3.96 euros; low-certainty evidence). We identified 29 ongoing trials, of which 15 were first posted or at least were last updated after 1 January 2018. AUTHORS' CONCLUSIONS: PNBs reduce pain on movement within 30 minutes after block placement, risk of acute confusional state, and probably also reduce the risk of chest infection and time to first mobilization. There may be a small reduction in the cost of analgesic drugs for single-injection PNB. We did not find a difference for myocardial infarction and mortality, but the numbers of participants included for these two outcomes were insufficient. Although randomized clinical trials may not be the best way to establish risks associated with an intervention, our review confirms low risks of permanent injury associated with PNBs, as found by others. Some trials are ongoing, but it is unclear whether any further RCTs should be registered, given the benefits found. Good-quality non-randomized trials with appropriate sample size may help to clarify the potential effects of PNBs on myocardial infarction and mortality.
Erector spinae block is an ultrasound-guided interfascial plane block first described in 2016. The objectives of this cadaveric dye injection and dissection study were to simulate an erector spinae ...block to determine if dye would spread anteriorly to the involve origins of the ventral and dorsal branches of the spinal nerves.
In 10 unembalmed human cadavers, 20 mL of 0.25% methylene blue dye was injected bilaterally into the plane between the fifth thoracic transverse process and erector spinae muscle. An in-plane ultrasound-guided technique with the transducer orientated longitudinally was used. During dissection, superficial and deep muscles were identified, and extent of dye spread was documented in cephalocaudal and lateral directions. The ventral and dorsal rami of spinal nerves and dorsal root ganglion at each level were examined to determine if they were stained by dye.
There was extensive cephalocaudad and lateral spread of dye deep and superficial to the erector spinae muscles. Except for 1 injection (from 20), the ventral rami were not stained by the dye. In only 2 injections did the dye track posteriorly through the costotransverse foramen to the dorsal root ganglion. In all other cases, the dorsal root ganglia were not involved in the dye injection. The dye stained the dorsal rami posterior to the costotransverse foramen.
There was no spread of dye anteriorly to the paravertebral space to involve origins of the ventral and dorsal branches of the thoracic spinal nerves. Dorsal ramus involvement was posterior to the costotransverse foramen.
Theoretically, the ideal volume of local anaesthetic for adductor canal block (ACB) would ensure sufficient filling of the canal and avoid proximal spread to the femoral triangle. In this ...dose-finding study, we aimed to investigate the minimal effective volume for an ACB needed to fill the adductor canal distally in at least 95% of patients (ED95).
We performed a blinded trial, enrolling 40 healthy men. All subjects received an ACB with lidocaine 1%. Volumes were assigned sequentially to the subjects using the continual reassessment method followed by Bayesian analysis to determine the ED95. Distal filling of the adductor canal was assessed by magnetic resonance imaging (primary outcome). Secondary outcomes were the effect of volume on proximal spread to the femoral triangle (also assessed by magnetic resonance imaging), quadriceps muscle weakness (decrease by ≥25% from baseline) and sensory block.
The ED95 was 20 ml, with an estimated probability of sufficiently filling the canal of 95.1% (95% credibility interval: 0.91–0.98). Proximal spread to the femoral triangle was seen in 0/4 (0%), 7/12 (58%), 4/8 (50%), and 8/16 (50%) subjects with the 5, 10, 15, and 20 ml doses, respectively (P=0.25). Seven subjects had a reduction in muscle strength, but there was no difference between groups (P=0.85).
For an ACB, the dose closest to the ED95 needed to fill the adductor canal distally was 20 ml. There was no significant correlation between volume and proximal spread or muscle strength.
NCT02033356.
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